Infusion of nonmyeloablative bone marrow alleviates acute rejection reaction in liver allotransplantation

Objective: To study the effect and implication of nonmyeloablative donor specific bone marrow (DSBM) infusion on the immunoreaction of liver allotransplantation. Methods: Orthotopic liver transplantation model was used in this study. Groups were set as follows: Group Ⅰ, syngeneic control (Wistar-to-Wistar); Group Ⅱ, acute rejection (SD-to-Wistar); Group Ⅲ, acute rejection treated with cyclosporine A (CsA) by intramuscular injection (SD-to-Wistar CsA); Group Ⅳ, bone marrow infusion at 7 d pretransplantation followed by short-term CsA treatment (SD-to-Wistar DSBM); Another group of short-term CsA treatment preoperatively without bone marrow infusion was also set as control. General characteristics and survival time were observed.Histological grades of rejection were determined by pathological examination. IL-2 and IFN-γ level in peripheral blood and donor liver were detected respectively by Enzyme-Linked Immuno-Sorbent Assay (ELISA) and Western blot. Chimerism of donor cells was measured by PCR for a male-specific marker (Y-chromosome-specific sequence, Sry). Results: No signs of rejection were found in Group Ⅰ. Acute rejection occurred in both Group Ⅱ and the short-term CsA treated group. All the recipients died at (9～15)d posttransplantation with a median survival time of (10.7±0.5) d and (11.2±2.4) d, respectively. Only mild rejection could be seen in Group Ⅲ. In Group Ⅳ, 4 out of 6 recipients had long-term survival (＞100 d), the histological grade of rejection was significantly lower than that of Group Ⅱ, so did the expression level of IL-2 and IFN-γ in both peripheral blood and grafted liver.Y-chromosome-specific sequence (Sry) of male SD rats could be detected in the bone marrow, spleen and thymus of female recipients at 15 d after bone marrow infusion. Conclusion: Mild preconditioning nonmyeloablative donor specific bone marrow infusion can enhance chimerism formation in recipients, alleviate the rejection of liver allotransplantation and prolong survival of liver allotransplantation.     

Suppressing progress of pancreatitis through selective inhibition of NF-κB activation by using NAC

Objective: To explore the characteristics of NF-κB activation in the progress of pancreatitis, the relationship with expression of TNF-α in the inflammatory reaction, and prevent the exacerbation of pancreatitis by using NAC. Method: Forty-eight rats were divided into three groups: therapy (group C), pancreatitis (group B) and control (group A). NAC served as the inhibitor of NF-κB activation. In the time intervals of 1.5, 3.0, 6.0, 12.0 hour, NF-κB activation was detected with flow cytometry (FCM) and the expression of TNF-α mRNA and protein with in situ hybridization (ISH) and enzyme-linked immuno-sorbent assay (ELISA) respectively. Meanwhile, the level of lipase and amylase in the serum was assayed and the pathological change was evaluated. Result: NF-κB activation in the pancreatitis group was higher than that in the control group (P<0.01), peaked at 3 hours, and was depressed by the inhibitor of NF-κB, NAC. The expression of TNF-α as well as the level of lipase and amylase in the serum also rose synchronously with activation of NF-κB. In contrast to group A, it was significantly different (P<0.01) in group B. After using NAC in group C, all of these values were decreased and the inflammatory reaction in the pancreas abated evidently. The pathology changes of the pancreas were shown to be alleviated in group C. Conclusion: First, NF-κB activity is intensively initiated in the course of pancreatitis and shown to have closely relationship with the release of cytokines. Second, use of NAC markedly depressed NF-κB activation. TNF-α expression is down regulated by cytokines. It is suggested that NAC probably acts as a useful agent for treatment of pancreatitis by indirectly inhibiting activation of NF-κB.     

Ds-echinoside A, a new triterpene glycoside derived from sea cucumber, exhibits antimetastatic activity via the inhibition of NF-κB-dependent MMP-9 and VEGF expressions

Ds-echinoside A (DSEA), a non-sulfated triterpene glycoside, was isolated from the sea cucumber Pearsonothuria graeffei. In vitro and in vivo investigations were conducted on the effects of DSEA on tumor cell adhesion, migration, invasion, and angiogenesis. In this study, we found that DSEA inhibited the proliferation of human hepatocellular liver carcinoma cells Hep G2, with a half-maximal inhibitory concentration (IC₅₀) of 2.65 μmol/L, and suppressed Hep G2 cell adhesion, migration, and invasion in a dose-dependent manner. DSEA also reduced tube formation of human endothelial cells ECV-304 on matrigel in vitro and attenuated neovascularization in the chick embryo chorioallantoic membrane (CAM) assay in vivo. Immunocytochemical analysis revealed that DSEA significantly decreased the expression of matrix metalloproteinase-9 (MMP-9), which plays an important role in the degradation of basement membrane in tumor metastasis and angiogenesis. DSEA also increased the protein expression level of tissue inhibitor of metalloproteinase-1 (TIMP-1), an important regulator of MMP-9 activation. From the results of Western blotting, the expressions of nuclear factor-kappa B (NF-κB) and vascular endothelial growth factor (VEGF) were found to be remarkably reduced by DSEA. These findings suggest that DSEA exhibits a significant antimetastatic activity through the specific inhibition of NF-κB-dependent MMP-9 and VEGF expressions.     

A novel way of liver preservation improves rat liver viability upon reperfusion

Background/aim： Currently, the liver is cold-preserved at 0-4 ℃ for experimental and clinical purposes. Here, we investigated whether milder hypothermia during the initial phase of the preservation period was beneficial for liver viability upon reperfusion. Methods： In the first set of experiments, rat livers were preserved either conventionally in clinically used histidine-trypthopan-ketoglutarate （HTK） solution （Group A： 45 min and Group B： 24 h） or by slow cooling HTK solution （from 13 ℃ to 3 ℃） during the initial 45 min of preservation （Group C： 24 h）. In the second set of experiments, additional groups of livers were evaluated： Group BB-preservation according to Group B and Group CC-preservation according to Group C. Further, some livers were preserved at 13 ℃ for 24 h. Livers were then reperfused using a blood-free perfusion model. Results： Bile production was approximately 2-fold greater in Group C compared to Group B. Alanine transaminase （ALT） and aspartate transaminase （AST） release into perfusate were 2-3-fold higher in Group B compared to Group C. No significant differences were found in ALT and AST release between Group C and Group A. Livers in Group CC compared to Group BB exhibited significantly lower portal resistance, greater oxygen consumption and bromosulfophthalein excretion into bile and lower lactate dehydrogenase （LDH） release into perfusate. Histological evaluation of tissue sections in Group BB showed parenchymal dystrophy of hepatocytes, while dystrophy ofhepatocytes was absent in Group CC. Livers preserved at 13 ℃ for 24 h exhibited severe ischemic injury Conclusion： These results suggest that the conventional way of liver preservation is not suitable at least for rat livers and that slow cooling of HTK solution during the initial phase of cold storage can improve liver viability during reperfusion.     

Research on the protection effect of pioglitazone for non-alcoholic fatty liver disease （NAFLD） in rats

Objective： The prevalence of non-alcoholic fatty liver disease （NAFLD） has markedly increased. Insulin resistance has been implicated in the pathogenesis of NAFLD. This study was aimed at observing the relationship between insulin resistance and NAFLD, and evaluating the role of pioglitazone （PGZ） acting as insulin-sensitizing agents in the prevention and treatment of rat fatty liver induced by high fat feeding. Methods： The rats were separated randomly into 6 groups： model group Ⅰ were fed high fat diet for 8 weeks, PGZ prevention group were given PGZ 4 mg/（kg.d） simultaneously, while control group Ⅰ were fed normal food for 8 weeks; model group Ⅱ were fed high fat diet for 16 weeks, PGZ treatment group were given PGZ 4 mg/（kg.d） orally simultaneous with high fat diet for 8 weeks after high fat feeding for 8 weeks, control group Ⅱ were fed normal food for 16 weeks. The rats were sacrificed after 8 weeks and 16 weeks respectively. Liver weight, body weight, serum activities of alanine aminotransferase （ALT）, aspartate aminotransferase （AST）, alkaline phosphatase （ALP）, tumor necrosis factor alpha （TNF-α）, fasting blood glucose （FBG）, fasting plasma insulin （FINS）, HOMA （homeostasis model assessment） insulin resistance index （HOMA-IR）, and the liver histology of rats of all groups were assayed. Results： After 8 weeks, the liver in model group Ⅰ showed typical steatosis, accompanied with mild to moderate lobular inflammatory cell infiltration, liver indexes and serum levels of ALT, AST, ALP, TNF-α were significantly increased （P〈0.05） compared with control group Ⅰ. Whereas, the degree of hepatic injury was attenuated in PGZ prevention group, liver indexes and serum levels of ALT, ALP were significantly decreased （P〈0.05） compared with model group Ⅰ. After 16 weeks, notable steatosis, and lobular inflammation were observed in model group Ⅱ rat liver, while the degree of hepatic injury was attenuated in the PGZ treatment group. Liver index, serum levels ofALT, AST, ALP, FINS and HOMA-IR were significantly increased （P〈0.05） in model group Ⅱ compared with control group Ⅱ. Whereas, in PGZ treatment group, serum levels of AST and FINS showed decreasing tendency, liver indexes, serum levels of ALT, ALP, TNF-α and HOMA-IR were significantly decreased compared with model group Ⅱ. Conclusion： Insulin resistance plays a role in the pathogenesis of NAFLD in rats. Pioglitazone can attenuate insulin resistance and biochemical and histological injury in high fat-induced fatty liver in rats.     

肝移植后肝功能异常的诊断及内科处理

已度过围手术期的肝移植患者,肝功能再次异常的原因主要包括原发病的复发,特别是乙型和丙型肝炎的复发、新病毒感染,特别是巨细胞病毒的感染、慢性排斥反应、排斥药物中毒所致肝损害等.临床诊断除常规检测肝功能外,主要依靠病毒学检测及病理诊断.内科治疗方法包括手术前的抗病毒治疗、预防呼吸道病毒感染、定期检测抗排斥药物的浓度、及时更换抗排斥药物等.     

Evaluation of orthotopic liver transplantation with no veno-venous bypass

Objective: To assess the feasibility and outcome of orthotopic liver transplantation (OLT) with no veno-venous bypass(v-v bypass) in adult patients. Methods: Between 1999 and 2001, 43 adult patients underwent OLT with v-v bypass, 33 with no v-v bypass. The operation time, anhepatic time, amount of blood loss, amount of blood transfusion, ICU stay days of the two groups were compared; renal function and gastrointestinal function in the two groups were examined. Results: There was no significant difference in mean serum creatinine on day 3 and gas discharge time in patients with v-v bypass or not. With no v-v bypass, the average operation time was 5.7±1.3 hours, anhepatic time was 64±13 minutes, median amount of blood loss in operation was 4000±820 mL, median amount of blood transfused intraoperatively was 4650±910 mL, median ICU stay was 5.7 days; all those were lower or shorter than those with v-v bypass; and these differences between the two groups had statistical significances. Conclusion: OLT with no v-v bypass is safe and can be performed in the majority of adult patients. The practice of liver transplantation with no v-v bypass is associated with shorter total operation time, shorter anhepatic time, lower blood product usage, and shorter ICU stay compared with standard technique of OLT with routine use of v-v bypass. Project supported by Zhejiang Provincial Health Bureau (No.2000/ZD003)     

Impairment of liver regeneration by the histone deacetylase inhibitor valproic acid in mice

Background and objective: Liver regeneration is a complex process regulated by a group of genetic and epigenetic factors. A variety of genetic factors have been reported, whereas few investigations have focused on epigenetic regulation during liver regeneration. In the present study, valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, was used to investigate the effect of HDAC on liver regeneration. Methods: VPA was administered via intraperitoneal injection to 2/3 partially hepatectomized mice to detect hepatocyte proliferation during liver regeneration. The mice were sacrificed, and their liver tissues were harvested at sequential time points from 0 to 168 h after treatment. DNA synthesis was detected via a BrdU assay, and cell proliferation was tested using Ki-67. The expressions of cyclin D1, cyclin E, cyclin dependent kinase 2 (CDK2), and CDK4 were detected by Western blot analysis. Chromatin immunoprecipitation (ChIP) assay was used to examine the recruitment of HDACs to the target promoter regions and the expression of the target gene was detected by Western blot. Results: Immunohistochemical analysis showed that cells positive for BrdU and Ki-67 decreased, and the peak of BrdU was delayed in the VPA-administered mice. Consistently, cyclin D1 expression was also delayed. We identified B-myc as a target gene of HDACs by complementary DNA (cDNA) microarray. The expression of B-myc increased in the VPA-administered mice after hepatectomy (PH). The ChIP assay confirmed the presence of HDACs at the B-myc promoter. Conclusions: HDAC activities are essential for liver regeneration. Inhibiting HDAC activities delays liver regeneration and induces liver cell cycle arrest, thereby causing an anti-proliferative effect on liver regeneration.     

Exosome-derived galectin-9 may be a novel predictor of rejection and prognosis after liver transplantation

Journal of Zhejiang University-SCIENCE B - Acute cellular rejection (ACR) remains a major concern after liver transplantation. Predicting and monitoring acute rejection by non-invasive methods are...     

Improved myocardial perfusion and cardiac function by controlled-release basic fibroblast growth factor using fibrin glue in a canine infarct model

Objective: Angiogenic therapy is emerging as a potential strategy for the treatment of ischemic heart disease but is limited by a relatively short half-life of growth factors.Fibrin glue (FG) provides a reservoir for controlledrelease of growth factors.The aim of this study was to evaluate the effects of basic fibroblast growth factor (bFGF) incorporating FG on angiogenesis and cardiac performance in a canine infarct model.Methods: Acute myocardial infarction was induced by ligation of the left anterior descending coronary artery (LAD).Group I (n=6) underwent ligation of LAD alone.In Group II,transmural channels were created in the infarct area (n=6).In Group III,nontransmural channels were created to locate FG cylinders containing bFGF (n=6).Eight weeks after operation,myocardial perfusion was assessed by single photon emission computed tomography,cardiac function by echocardiography,and vascular development by immunohistochemical staining.Results: Total vascular density and the number of large vessels (internal diameter ≥50 μm) were dramatically higher in Group III than in Groups I and II at eight weeks.Only the controlled-release group exhibited an improvement in regional myocardial perfusion associated with lower defect score.Animals in Group III presented improved cardiac regional systolic and diastolic functions as well as global systolic function in comparison with the other two groups.Conclusions: Enhanced and sustained angiogenic response can be achieved by controlled-release bFGF incorporating FG within transmyocardial laser channels,thus enabling improvement in myocardial perfusion and cardiac function.     

Anticoagulation therapy in intra-aortic balloon counterpulsation: Does IABP really need anti-coagulation?

Objective: To investigate if intra-aortic balloon pump(IABP) is contraindicated without anticoagulation therapy. Methods: Some 153 IABP patients in the King Abdulaziz Cardiac Center(KSA) were randomly assigned into two groups. Anticoagulation group (Group A) consisted of 71 patients who were given heparin intravenously with target aPTT50–70 seconds. Non-anticoagulation group (Group B) consisted of 82 patients without intravenous heparin during balloon pumping. Hematological parameters including platelet count, D-dimer, Plasminogen activator inhibitor-1 (PAI-1) and fibrinogen degradation products (FDP) were checked respectively at the point of baseline, 24 hours, 48 hours and 24 hours post IABP counterpulsation. Clot deposits on balloon surface, vascular complications from IABP including bleeding and limb ischemia were recorded. Results: Platelet count and PAI-1 level decreased at 24 hours and 48 hours in both groups (P<0.05). D-dimer dimer and FDP level increased at 24 hours and 48 hours in both groups(P<0.05), but returned to the baseline level 24 hours post IABP removal (P>0.05). Three patients in Group A and 2 patients in Group B developed minor limb ischemia (P>0.05). No major limb ischemia in either group. Two patients in Group A suffered major bleeding and required blood transfusion or surgical intervention, whereas no patient had major bleeding in Group B. Eight patients had minor bleeding in Group A, but only 2 patients in Group B (P<0.05). No clot deposit developed on IABP surface in either group. Conclusion: IABP is safe without routine anticoagulation therapy. Selecting appropriate artery approach and early detection intervention are key methods for preventing complications.     

Effects of combination of irbesartan and perindopril on calcineurin expression and sarcoplasmic reticulum Ca2＋-ATPase activity in rat cardiac pressure-overload hypertrophy

INTRODUCTION Left ventricular hypertrophy has been thought to be the principal predicators of predisposing risk factor of cardiac morbidity and mortality (Devereux, 1995; Levy et al., 1990). The pathogenesis that mediates cardiac hypertrophy is poorly understood. Cardiachypertrophy can be induced by hemodynamic over-load, ischemic disease, neurohumoral factors and intrinsic defects in cardiac structural protein genes (Sadoshima and Izumo, 1997; Vikstrom and Lein-wand, 1996). Another in…     

Structural changes of oviduct of freshwater shrimp, Macrobrachium nipponense （Decapoda, Palaemonidae）, during spawning

The structural change of the oviduct of freshwater shrimp （Macrobrachium nipponense） during spawning was examined by electron microscopy. The oviduct wall structural characteristics seem to be influenced significantly by the spawning process. Before the parturition and ovulation, two types of epithelial cells （types Ⅰ and Ⅱ） are found in the epithelium. The free surfaces of type Ⅰ and type Ⅱ cells have very dense long microvilli. Under the type Ⅰ and type Ⅱ cells, are a relatively thick layer of secreting material and a layer of mostly dead cells. After ovulation, two other types of epithelial cells （types Ⅲ and Ⅳ） are found in the oviduct wall epithelium. The free surface of type Ⅲ cells only has short microvilli scattered on the surface. The thick layer with secreting material and the dead cell layer disappeared at this stage. In some type Ⅲ cells, the leaking out of cytoplasm from broken cell membrane led to the death of these type Ⅲ cells. The transformation of all four types of epithelial cells was in the order： Ⅳ→Ⅰ→Ⅱ→Ⅲ.     

Allograft rejection-related gene expression in the endothelial cells of renal transplantation recipients after cytomegalovirus infection

Objective: To explore the effects of cytomegalovirus (CMV) infection on rejection-related gene expression in the endothelial cells of renal transplantation recipients. Methods: Endothelial cells (ECs) were cultured and stimulated by a variety of factors: A, normal control group; B, inactivated human cytomegalovirus (HCMV) infection group; C, HCMV infection group; D, HCMV supematant infection group; and E, ganciclovir HCMV group. Expression of intercellular adhesion molecule-1 (ICAM-1) and major histocompability complex (MHC) class Ⅰ and class Ⅱ antigens was detected by flow cytometry (FCM) and immuno-histochemistry. Results: We found characteristic CMV-infected ECs in this study. There were no significant differences among groups A, B and D (P>0.05). Although the expression levels of ICAM-1 were not significantly different between groups C and E (P>0.05), the ICAM-1 expression in these two groups was significantly higher than that in group A (P<0.05). ICAM-1 expression was detected in groups C and E, while there was no expression in groups A, B and D. Furthermore, there was no significant difference of ICAM-1 mRNA expression between groups C and E (P>0.05). Human leucocyte antigen (HLA)-ABC expression was detected in all the groups, while HLA-DR expression was only detected in groups C and E. There were no significant dif-ferences of HLA-ABC and HLA-DR expression among groups A, B and D (P>0.05). However, the HLA-ABC and HLA-DR expression levels in groups C and D were higher than those of the remaining groups previously reported (P<0.05). Meanwhile, the HLA-ABC and HLA-DR expression levels in group E were lower than those of group C (P<0.05). Conclusion: CMV could up-regulate the expression levels of ICAM-1 and MHC antigens, which was closely related to allograft rejection.     

丹参注射液治疗肝纤维化的实验研究

目的探讨丹参注射液抗肝纤维化作用机理.方法取40只成年wistar大鼠,利用猪血清腹腔注射法,连续6周,复制免疫性肝纤维化模型.治疗组采用大、小剂量丹参液肌肉注射,其剂量分别为0.3ml/kg和0.15ml/kg,每日一次,连续4周.取肝脏切片,HE和Mollory染色,光镜下观察.检测血清SOD活性、MDA含量和肝功能.结果大剂量治疗组肝细胞空泡减少,胶原纤维大部分消失,SOD活性增高,MDA含量降低,与模型组比较有显著性差异(P＜0.05).结论大剂量肌注丹参液,具有治疗肝纤维化的功能.     

Intestinal microflora in rats with ischemia／reperfusion liver injury

Objectives:To investigate the intestinal microflora status related to ischemia/reperfusion(I/R)liver injury and explorethe possible mechanism.Methods:Specific pathogen free grade Sprague-Dawley rats were randomized into three groups:Controlgroup(n=8),sham group(n=6)and I/R group(n=10).Rats in the control group did not receive any treatment,rats in the I/R groupwere subjected to 20 min of liver ischemia,and rats in the sham group were only subjected to sham operation.Twenty-two hourslater,the rats were sacrificed and liver enzymes and malondialdehyde(MDA),superoxide dismutase(SOD),serum endotoxin,intestinal bacterial counts,intestinal mucosal histology,bacterial translocation to mesenteric lymph nodes,liver,spleen,andkidney were studied.Results:Ischemia/reperfusion increased liver enzymes,MDA,decreased SOD,and was associated withplasma endotoxin elevation in the I/R group campared to those in the sham group.Intestinal Bifidobacteria and Lactobacillidecreased and intestinal Enterobacterium and Enterococcus     

Influence of fasting on muscle composition and antioxidant defenses of market-size Sparus macrocephalus

The study was conducted to investigate fasting effects on flesh composition and antioxidant defenses of market-size Sparus macrocephalus. Two hundred fish (main initial weight 580 g) were divided into two groups (control and fasted) and reared in 6 cages. After two weeks of adaptation, group I fasted for 28 d; group II was fed normally as a control. In 3, 7, 14, 21 and 28 d, 6 fish per group were sampled for proximate flesh composition, liver antioxidant enzyme activities and malondialdehyde flesh content analyses. In fasted fish, the reduction of lipid content in muscle occurred after day 3, and, compared to controls, the content of protein decreased from day 14, the activities of liver antioxidative enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPX) increased from day 3, and flesh malondialdehyde levels increased from day 21. Flesh fat reduction shows that fasting may be used as a technique to reduce flesh lipid content in Sparus macrocephalus. However, considering flesh protein loss and the subsequent oxidative stress, the fasting technique should be used with precautions. Project (No. 2006C12098) supported by the Science and Technology Department of Zhejiang Province, China     

RNA干扰T细胞mTOR表达后诱导T细胞分化对小肠移植耐受的影响

目的:探讨RNA干扰T细胞mTOR表达后诱导T细胞分化对小肠移植免疫耐受的影响。方法:通过shRNA干扰T细胞mTOR表达后,诱导T细胞向Foxp3+Tregs细胞分化。对60只雄性SD大鼠施行30次异位节段小肠移植,随机分为A组(mTOR-shRNA转染组)、B组(mTOR抑制剂RAD001干预)和C组(移植对照组、注射生理盐水)。观察小肠移植后受体大鼠的体重变化、生存时间及移植小肠病理切片评估排斥反应程度。结果:构建的mTOR-shRNA质粒表达载体在体外能有效地抑制大鼠骨髓细胞mTOR基因mRNA和蛋白的表达。RNA干扰大鼠T细胞mTOR基因可调节T细胞的定向分化,Tregs细胞增多,而Th17细胞分化减少。抑制mTOR基因可诱导大鼠异位小肠移植的免疫耐受,减轻受体抗移植物的排斥反应,显著延长移植物的存活时间。结论:RNA干扰T细胞mTOR表达后诱导T细胞分化对小肠移植耐受的研究为mTOR抑制剂(RAD001)在移植后的临床应用提供理论和实验依据。     

Stereoselective glucuronidation of carvedilol by Chinese liver microsomes

Objective: To study the stereoselective glucuronidation of carvedilol (CARV) by three Chinese liver microsomes. Methods: The metabolites of CARV were identified by a hydrolysis reaction with β-glucuronidase and HPLC-MS/MS. The enzyme kinetics for CARV enantiomers glucuronidation was determined by a reversed phase-high pressure liquid chromatogra-phy (RP-HPLC) assay using (S)-propafenone as internal standard after precolumn derivatization with 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosylisothiocyanate. Results: Two CARV glucuronides were found in three Chinese liver microsomes incubated with CARV. The non-linear regression analysis showed that the values of Km and Vmax for (S)-CARV and (R)-CARV enantiomers were (118±44) μmol/L, (2 500±833) pmol/(min·mg protein) and (24±7) μmol/L, (953±399) pmol/(min·mg protein), respectively. Conclusion: These results suggested that there was a significant (P<0.05) stereoselective glucuronidation of CARV enantiomers in three Chinese liver microsomes, which might partly explain the enantioselective pharmacokinetics of CARV.