Study progress on mechanism of severe acute pancreatitis complicated with hepatic injury

Study on the action mechanism of inflammatory mediators generated by the severe acute pancreatitis(SAP) in mul-tiple organ injury is a hotspot in the surgical field.In clinical practice,the main complicated organ dysfunctions are shock,res-piratory failure,renal failure,encephalopathy,with the rate of hepatic diseases being closely next to them.The hepatic injury caused by SAP cannot only aggravate the state of pancreatitis,but also develop into hepatic failure and cause patient death.Its complicated pathogenic mechanism is an obstacle in clinical treatment.Among many pathogenic factors,the changes of vasoac-tive substances,participation of inflammatory mediators as well as OFR(oxygen free radical),endotoxin,etc.may play important roles in its progression.     

Review:Mechanism of acute pancreatitis complicated with injury of intestinal mucosa barrier

Acute pancreatitis (AP) is a common acute abdomen in clinic with a rapid onset and dangerous pathogenetic condition. AP can cause an injury of intestinal mucosa barrier, leading to translocation of bacteria or endotoxin through multiple routes, bacterial translocation (BT), gutorigin endotoxaemia, and secondary infection of pancreatic tissue, and then cause systemic in- flammatory response syndrome (SIRS) or multiple organ dysfunction syndrome (MODS), which are important factors influencing AP’s severity and mortality. Meanwhile, the injury of intestinal mucosa barrier plays a key role in AP’s process. Therefore, it is clinically important to study the relationship between the injury of intestinal mucosa barrier and AP. In addition, many factors such as microcirculation disturbance, ischemical reperfusion injury, excessive release of inflammatory mediators and apoptosis may also play important roles in the damage of intestinal mucosa barrier. In this review, we summarize studies on mechanisms of AP.     

Mechanism of acute pancreatitis complicated with injury of intestinal mucosa barrier

Acute pancreatitis （AP） is a common acute abdomen in clinic with a rapid onset and dangerous pathogenetic condition AP can cause an injury of intestinal mucosa barrier, leading to translocation of bacteria or endotoxin through multiple routes, bacterial translocation （BT）, gutorigin endotoxaemia, and secondary infection of pancreatic tissue, and then cause systemic inflammatory response syndrome （SIRS） or multiple organ dysfunction syndrome （MODS）, which are important factors influencing AP＇s severity and mortality. Meanwhile, the injury of intestinal mucosa barrier plays a key role in AP＇s process. Therefore, it is clinically important to study the relationship between the injury of intestinal mucosa barrier and AP. In addition, many factors such as microcirculation disturbance, ischemical reperfusion injury, excessive release of inflammatory mediators and apoptosis may also play important roles in the damage of intestinal mucosa barrier. In this review, we summarize studies on mechanisms of AP.     

Study progress in therapeutic effects of traditional Chinese medicine monomer in severe acute pancreatitis

INTRODUCTION Severe acute pancreatitis (SAP) is one of the three main acute abdominal problems always ac-companied by multiple-system and multiple-organ impaired function or failure. Its onset and develop-ment are characterized by rapid changes, complicated illness state and difficult treatment. With the con-tinuous development of the traditional Chinese medicine industry in recent years, it is proved that traditional Chinese medicine (TCM) monomers monomers have a marked effect for …     

Review:Study progress in therapeutic effects of traditional Chinese medicine monomer in severe acute pancreautis

Severe acute pancreatitis (SAP) is a common acute abdomen clinical problem characterized by high mortality, multiple complications, complicated pathogenesis and difficult treatment. Recent studies found traditional Chinese medicine (TCM)monomers have markedly good effect for treating SAP. Many TCM monomers can inhibit pancreatin, resist inflammation, improve microcirculation and immunoloregulation, etc. to block the pathological progress of SAP in multiple ways, reduce complications and lower mortality with rapid effects. It is significant for enhancing SAP treatment to deeply understand the current situation in TCM monomers for treating SAP and take precious references therein. This article summarizes the treating effects and mechanisms of TCM monomers for SAP in recent years.     

Advances in researches on the immune dysregulation and therapy of severe acute pancreatitis

During the development and progression of severe acute pancreatitis (SAP), conspicuous immune dysregulation develops, which is mainly manifested as excessive immune response in the early stage and immunosuppression in the late stage.This process involves complex changes in a variety of immune molecules and cells, such as cytokines, complements, lymphocytes,and leukocytes. With the gradual deepening of studies on the development and progression of SAP, the role of immune dysregulation in the pathogenesis of SAP has attracted more and more attention. In this article, we review the advances in research on the immune dysregulation in SAP and the immunotherapy of this disease through exploring the formation of excessive immune response and immune suppression as well as their mutual transformation.     

地塞米松可以减少由重症急性胰腺炎引起的肾脏微血管内皮糖萼的损伤（英文）

目的:明确地塞米松可以减少重症急性胰腺炎(SAP)引起的肿瘤坏死因子(TNF-α)的释放,减轻TNF-α导致的肾脏血管内皮糖萼的降解,从而改善肾脏微循环和缓解肾损伤。创新点:本研究通过小鼠活体研究的方法,建立小鼠重症急性胰腺炎模型,并用地塞米松进行干预对照,采用透射电镜、激光多谱勒和酶联免疫的方法,检测了各组小鼠肾脏血管内皮糖萼的完整性、肾血流灌注和TNF-α表达情况,阐明了地塞米松对内皮糖萼的保护作用。方法:通过"胰管结扎+腹腔内雨蛙素注射"的方法建立SAP模型,分别留取各组小鼠的血液和组织标本,采用透射电镜观察内皮糖萼的损伤情况,用酶联免疫检测血清TNF-α和糖萼成份多配体聚糖的浓度,并用激光多谱勒检测活体小鼠肾脏的灌注,分析地塞米松对内皮糖萼的保护和改善肾脏灌注的作用。结论:SAP可以引起TNF-α的大量释放,并导致内皮糖萼的降解和肾脏灌注下降,而地塞米松可以减少TNF-α的释放,减轻糖萼的降解,改善肾脏血流灌注。     

Clodronate-containing liposomes attenuate lung injury in rats with severe acute pancreatitis

Objectives:Severe acute pancreatitis(SAP) can lead to acute lung injury(ALI) .The purpose of this paper is to investigate the protective effect of clodronate-containing liposomes on ALI in rats with SAP.Methods:The thin film method was used to prepare liposomes.Sprague-Dawley rats were randomly divided into three groups.After the SAP model was established by injecting 5%(w/v) sodium taurocholate(2 ml/kg body weight) into the subcapsular space of the pancreata,normal saline was administered to the control(C) group,phosphate buffer solution(PBS) -containing liposome to the Pgroup,and clodronate-containing liposome to the Tgroup through tail veins.Blood samples were obtained from the superior mesenteric vein at 2 and 6 h to measure the levels of amylase,interleukin-6(IL-6) ,and tumor necrosis factor-α(TNF-α) .Morphological changes in the pancreata and lung were observed using hematoxylin and eosin(HE) staining,while cell apoptosis was detected using terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling(TUNEL) .In addition,the macrophage marker cluster of differentiation 68(CD68) in lung tissue was detected with immunohistochemistry.Results:Blood levels of amylase,IL-6,and TNF-αwere significantly increased in the Pgroup compared to those in the Tgroup(P0.05) .In the Tgroup,large numbers of TUNEL-positive cells were observed,but no or few in the C and Pgroups.Gross inspection and HE staining of pancreata and lung showed dramatic tissue damage,including inflammation and necrosis in the Pgroup.Less remarkable changes were noted in the Tgroup,and the C group exhibited normal histology.The histological scores according to Kaiser's criteria were consistent with HE findings.The number of CD68-positive macrophages decreased in the Tgroup.Conclusions:Clodronate-containing liposomes have a protective effect against ALI in rats with SAP.Blockade of macrophages may represent a novel therapeutic strategy in SAP.     

Clodronate-superparamagnetic iron oxide-containing liposomes attenuate renal injury in rats with severe acute pancreatitis

Background and objective

It has been shown that macrophages play an important role in the development of severe acute pancreatitis (SAP), and eventually lead to multiple organ failure (MOF). Clodronate-liposome selectively depleted macrophages. This study was to investigate the role of renal macrophage infiltration in acute renal injury in rats with SAP and to evaluate the potential of superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance imaging (MRI) for diagnosis.

Methods

Superparamagnetic Fe₃O₄ nanoparticles were prepared by chemical coprecipitation. SPIO-liposomes and SPIO-clodronate-liposomes were prepared by the thin film method. SAP models were prepared by injection of sodium taurocholate into the subcapsular space of rat pancreas. Sprague-Dawley rats were randomly divided into a control group, SAP plus SPIO-liposome (P) group, and SAP plus SPIO-clodronate-containing liposome (T) group. Kidney injury was evaluated by T2-weighted MRI scan. The levels of serum amylase (SAM), blood urea nitrogen (BUN), and serum creatinine (SCr) were measured by an automated enzymatic method. Serum tumor necrosis factor-α (TNF-α) was measured by enzyme-linked immunosorbent assay (ELISA). Pathological changes in the pancreas and kidney were observed using hematoxylin and eosin (H&E) staining, while cell apoptosis was detected with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. In addition, the macrophage markers (CD68) of the renal tissue were detected with immunohistochemistry.

Results

The pathological changes in the pancreas and kidneys of rats in the T group were milder than those in the P group. The MRI signal intensity of the kidneys in the P and T groups was significantly lower than that in the control group. There were significant changes in the two experimental groups (P<0.01). The levels of SAM, Bun, SCr, and TNF-α in rats in the P group were higher than those in the control group (P<0.01) and in the T group (P<0.01). The apoptosis of the kidney in the T group was higher than that in the P group at 2 and 6 h (P<0.01).

Conclusions

Clodronate-containing liposomes protected against renal injury in SAP rats, and SPIO can be used as a tracer for MRI examination to detect renal injury in SAP rats. SPIO-aided MRI provided an efficient non-invasive way to monitor the migration of macrophages after renal injury in rats with SAP.     

Protective effects of Salvia miltiorrhizae on the hearts of rats with severe acute pancreatits or obstructive jaundice

Objective: To investigate the therapeutic effects and mechanisms of Salvia miltiorrhizae (Danshen) in the treatment of severe acute panereatitis (SAP)- or obstructive jaundice (OJ)-induced heart injury. Methods: A total of 288 rats were used for SAP-(n=108) and O J-associated (n=180) experiments. The rats were randomly divided into sham-operated, model control, and Salvia miltiorrhizae-treated groups. According to the difference of time points after operation, SAP rats in each group were subdivided into 3, 6 and 12 h subgroups (n=12), whereas OJ rats were subdivided into 7, 14, 21, and 28 d subgroups (n=15). At the corre-sponding time points after operation, the mortality rates of the rats, the contents of endotoxin and phospholipase A2 (PLA2) in blood, and pathological changes of the hearts were investigated. Results: The numbers of dead SAP and OJ rats in the treated groups declined as compared with those in the model control group, but not significantly (P>0.05). The contents ofendotoxin (at 6 and 12 h in SAP rats and on 7, 14, 21, and 28 d in OJ rats, respectively) and PLA2 (at 6 and 12 h in SAP rats and on 28 d in OJ rats, respectively) in the treated group were significantly lower than those in the model control group (P<0.01 and P<0.001, respec-tively). Besides, myocardial pathological injuries were mitigated in SAP and OJ rats. Conclusion: In this study, we found that Salvia miltiorrhizae improved myocardial pathological changes, reduced the content of PLA2 in blood, and decreased the mortality rates of SAP and OJ rats, exerting protective effects on the hearts of the rats.     

Protective effects of Salvia miltiorrhizae on the hearts of rats with severe acute pancreatits or obstructive jaundice

Objective  To investigate the therapeutic effects and mechanisms of Salvia miltiorrhizae (Danshen) in the treatment of severe acute pancreatitis (SAP)- or obstructive jaundice (OJ)-induced heart injury. Methods  A total of 288 rats were used for SAP- (n=108) and OJ-associated (n=180) experiments. The rats were randomly divided into sham-operated, model control, and Salvia miltiorrhizae-treated groups. According to the difference of time points after operation, SAP rats in each group were subdivided into 3, 6 and 12 h subgroups (n=12), whereas OJ rats were subdivided into 7, 14, 21, and 28 d subgroups (n=15). At the corresponding time points after operation, the mortality rates of the rats, the contents of endotoxin and phospholipase A₂ (PLA₂) in blood, and pathological changes of the hearts were investigated. Results  The numbers of dead SAP and OJ rats in the treated groups declined as compared with those in the model control group, but not significantly (P>0.05). The contents of endotoxin (at 6 and 12 h in SAP rats and on 7, 14, 21, and 28 d in OJ rats, respectively) and PLA₂ (at 6 and 12 h in SAP rats and on 28 d in OJ rats, respectively) in the treated group were significantly lower than those in the model control group (P<0.01 and P<0.001, respectively). Besides, myocardial pathological injuries were mitigated in SAP and OJ rats. Conclusion  In this study, we found that Salvia miltiorrhizae improved myocardial pathological changes, reduced the content of PLA₂ in blood, and decreased the mortality rates of SAP and OJ rats, exerting protective effects on the hearts of the rats. Projected supported by the Technological Foundation Project of Traditional Chinese Medicine Science of Zhejiang Province (Nos. 2003C130 and 2004C142), the Grave Foundation Project for Technological and Development of Hangzhou City (No. 2003123B19), and the Intensive Foundation Project for Technology of Hangzhou City (No. 2004Z006), China     

Review:Acute lung injury/acute respiratory distress syndrome (ALI/ARDS): the mechanism,present strategies and future perspectives of therapies

INTRODUCTION OF ACUTE LUNG IN- JURY/ACUTE RESPIRATORY DISTRESS SYN- DROME (ALI/ARDS) Acute lung injury (ALI) and its more severe form, the acute respiratory distress syndrome (ARDS) are syndromes of acute respiratory failure, which was defined by radiological (bilateral lung field infiltrates) and physiological (the ratio of arterial oxygen pres- sure and the inspiratory oxygen concentration, Pa O 2 /Fi O2≤300 mmHg for ALI and ≤200 mmHg for ARDS) criteria in…     

鬼针草总黄酮对小鼠急性肝损伤的影响

将66只昆明小鼠随机分为11组：正常组、模型组及鬼针草全草、叶和枝总黄酮治疗组,每治疗组分为低、中和高剂量（40、80、160 mg/kg）亚组,鬼针草总黄酮（TFB）采用正交试验法提取.治疗组连续灌胃14 d后以四氯化碳（CCl4）建立小鼠急性肝损伤模型,IFCC速率法检测小鼠血清中丙氨酸氨基转移酶（alanine transaminase, ALT）、天冬氨酸氨基转移酶（aspartate transaminase,AST）和乳酸脱氢酶（lactate dehydrogenase,LDH）活性.观察不同生理部位TFB对小鼠急性肝损伤时肝功能的影响,探讨其肝损伤保护作用.结果表明：与模型组相比,叶和全草TFB（40 mg/kg）和枝TFB（80 mg/kg）能极显著降低ALT含量（P＜0.01）;仅有叶TFB（40 mg/kg）能极显著降低AST含量（P＜0.01）,而枝TFB（160 mg/kg）能极显著升高AST（P＜0.01）含量;叶和全草TFB在40 mg/kg时LDH活性极显著降低（P＜0.01）.提示鬼针草不同生理部位TFB在急性肝损伤中的作用不同,仅有叶TFB在低剂量（40 mg/kg）时表现出较好的肝保护作用,其余鬼针草各组提示可能肝毒性较大.     

Effects of dexamethasone and Salvia miltiorrhiza on multiple organs in rats with severe acute pancreatitis

Objective: To investigate the protective effects and mechanisms of action of dexamethasone and Salvia miltiorrhiza on multiple organs in rats with severe acute pancreatitis (SAP). Methods: The rats were divided into sham-operated, model control, dexamethasone treated, and Salvia miltiorrhiza treated groups. At 3, 6, and 12 h after operation, the mortality rate of different groups, pathological changes, Bcl-2-associated X protein (Bax) and nuclear factor-κB (NF-κB) protein expression levels in multiple organs (the pancreas, liver, kidneys, and lungs), toll-like receptor 4 (TLR-4) protein levels (only in the liver), intercellular adhesion molecule 1 (ICAM-1) protein levels (only in the lung), and terminal deoxynucleotidy transferase mediated deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) staining expression levels, as well as the serum contents of amylase, glutamate-pyruvate transaminase (GPT), glutamic-oxaloacetic transaminase (GOT), blood urea nitrogen (BUN), and creatinine (CREA) were observed. Results: The mortality rate of the dexamethasone treated group was significantly lower than that of the model control group (P<0.05). The pathological changes in multiple organs in the two treated groups were relieved to different degrees (P<0.05 and P<0.01, respectively), the expression levels of Bax and NF-κB proteins, and apoptotic indexes of multiple organs were reduced (P<0.05 and P<0.01, respectively). The contents of amylase, GPT, GOT, BUN, and CREA in the two treated groups were significantly lower than those in model control groups (P<0.05 and P<0.01, respectively). The expression level of ICAM-1 protein in the lungs (at 3 and 12 h) in the dexamethasone treated group was significantly lower than that in the Salvia miltiorrhiza treated group (P<0.05). The serum contents of CREA (at 12 h) and BUN (at 6 h) of the Salvia miltiorrhiza treated group were significantly lower than those in the dexamethasone treated group (P<0.05). Conclusions: Both dexamethasone and Salvia miltiorrhiza can reduce the inflammatory reaction, regulate apoptosis, and thus protect multiple organs of rats with SAP.     

Acute lung injury/acute respiratory distress syndrome （ALI/ARDS）： the mechanism, present strategies and future perspectives of therapies

Acute lung injury/acute respiratory distress syndrome （ALI/ARDS）, which manifests as non-cardiogcnic pulmonary edema, respiratory distress and hypoxemia, could be resulted from various processes that directly or indirectly injure the lung. Extensive investigations in experimental models and humans with ALI/ARDS have revealed many molecular mechanisms that offer therapeutic opportunities for cell or gene therapy. Herein the present strategies and future perspectives of the treatment for ALI/ARDS, include the ventilatory, pharmacological, as well as cell therapies.