蜡菊乙醇提取物对庆大霉素诱导的大鼠肾毒性的影响（英文）

目的:评估蜡菊乙醇提取物(HPE)对庆大霉素诱导的肾毒性的治疗或保护作用。方法:将36只体重200~250 g的Sprague Dawley雄性大鼠分成6组,每组6只,适应实验室条件7 d。每组处理方式不同,包括:组Ⅰ,对照组,5%DMSO;组Ⅱ,HPE 100 mg/(kg·d);组Ⅲ,HPE200 mg/(kg·d);组Ⅳ,庆大霉素80 mg/(kg·d);组Ⅴ,庆大霉素80 mg/(kg·d)+HPE 100 mg/(kg·d);组Ⅵ,庆大霉素80 mg/(kg·d)+HPE 200 mg/(kg·d)。腹腔注射8 d后,取血清、肝和肾组织用于评估血液尿素氮(BUN)、肌酐、酶和非酶抗氧化剂和脂质过氧化。结论:庆大霉素能显著提升血清BUN、肌酐和肝肾阳性以及丙二醛(MDA)水平,同时降低过氧化氢酶(CAT),谷胱甘肽过氧化物酶(GPx)和超氧化物歧化酶(SOD)的活性。用100 mg/kg HPE的治疗能逆转庆大霉素诱导的改变。因此,100 mg/kg HPE在肾脏和肝脏中可作为自由基和清除剂,具有缓解庆大霉素在生物化学和组织病理学上毒性的作用。     

人参皂苷Rg1的抗抑郁作用及其作用机制

目的：观察人参皂苷Rg1的抗抑郁作用,探讨其抗抑郁机制。方法：采用小鼠悬尾实验（tail suspension test,TST）和强迫游泳实验（forced swim test,FST）建立急性应激模型,选择大鼠慢性温和不可预见性应激（chronic unpredictable mild stress,CUMS）的方法建立长期抑郁模型。同时给予人参皂苷Rg1（5,10,20 mg·kg-1·d-1）和度洛西汀（10 mg·kg-1·d-1）,观察Rg1的抗抑郁作用。结果：在急性应激实验中,Rg1三个剂量组（5,10,20 mg·kg-1）均能够显著减少动物的不动时间。慢性应激后,采用强迫游泳和糖水消耗实验进行行为学检测,与模型组相比,Rg1三个剂量均能够显著减少大鼠在强迫游泳实验中的不动时间,增加糖水偏好实验的糖水消耗百分比,延长动物的睡眠时间。机制研究证明,Rg1可抑制PDE4引起环腺苷酸（cyclic adenosine monophsphate,cAMP）的累积,进而激活cAMP介导的抗抑郁信号转导途径,还可增加雄激素水平,而雄激素又能拮抗糖皮质激素的释放和增加基础突触传递。此外,增加突触新生也是抗抑郁的重要机制。结论：人参皂苷Rg1对小鼠急性应激和CUMS诱导的大鼠抑郁行为有显著的改善作用,并可能通过调节神经递质和激素的释放、减少糖皮质激素含量、增加神经营养因子的表达以及增强突触可塑性来发挥抗抑郁作用。     

低胆固醇林蛙卵油和植物甾醇(豆甾醇)在大鼠中的降脂作用（英文）

目的:探索林蛙副产物林蛙卵油的开发价值。创新点:首次验证了低胆固醇林蛙卵油的减重降脂功能。方法:Sprague-Dawley大鼠连续被灌胃8周后,分成8组:(1)对照组喂食标准饲料;(2)高脂组喂食60%高脂饲料;(3)阳性对照组喂食3.33 mg/(kg·d)辛伐他汀;(4)OORC组喂食2 g/(kg·d)的低胆固醇林蛙卵油(OORC);(5)植物甾醇组喂食0.48g/(kg·d)的豆甾醇;(6)低剂量组喂食1g/(kg·d)的低胆固醇OORC和0.24g/(kg·d)的豆甾醇;(7)中剂量组喂食2g/(kg·d)的低胆固醇OORC和0.48 g/(kg·d)的豆甾醇;(8)高剂量组喂食4 g/(kg·d)的低胆固醇OORC和0.96 g/(kg·d)的豆甾醇。经过不同方法处理后,比较各组大鼠的体重、器官指数,以及血清中总胆固醇、甘油三酯、低密度脂蛋白和高密度脂蛋白浓度。同时,对动物肝脏进行组织切片染色并评价损伤情况。结论:低胆固醇林蛙卵油或者其与植物甾醇(如豆甾醇)联用可以预防高脂饮食诱导的增重、肝损伤和高血脂症状。     

人参皂苷Rg2对离体大鼠胸主动脉平滑肌的作用及作用机制研究

目的:研究人参皂苷Rg2(G-Rg2)对离体大鼠胸主动脉平滑肌的作用,并且对其作用机制进行初步探讨。方法:采用离体血管环技术制备离体大鼠胸主动脉环模型,采用血管收缩率为考察指标,设置内皮完整组和内皮去除组,记录人参皂苷Rg2(G-Rg2)对去甲肾上腺素(NE)预收缩大鼠胸主动脉环张力的变化影响。分别以L-NAME、ODQ、Indomethacin预孵育内皮完整血管环后,考察人参皂苷Rg2(G-Rg2)对去甲肾上腺素(NE)预收缩血管环的舒张作用;加入10^-3 mol/L的人参皂苷Rg2孵育去内皮血管后,用不同浓度的NE、KCl、CaCl₂收缩血管,观察血管的舒张作用。结果:与空白对照比较,10^-5、10^-4、10^-3、10^-2 mol/L的人参皂苷Rg2(G-Rg2)能显著提高经NE预收缩的内皮完整的血管环的舒张率(P<0.01),且呈浓度依赖趋势;经L-NAME、ODQ、Indomethacin预孵育内皮完整血管后,不同浓度的人参皂苷Rg2(G-R...     

α-硫辛酸对热应激小鼠睾酮分泌失调的保护作用

目的:研究α-硫辛酸对热应激引起小鼠睾酮分泌失调的保护作用.方法:将性成熟雄性SPF昆明小鼠60只,随机分为3组,即对照组、热应激组和α-硫辛酸+热应激处理组.分别采用酶联免疫吸附测定法(ELISA)检测各组小鼠血清睾酮含量,石蜡切片免疫组化染色法(IHC)分析各组小鼠非折叠蛋白反应信号通路的关键信号转导调节分子肌醇需求酶1(IRE1)在睾丸中的表达定位,以及蛋白免疫印迹法(Western blot)检测各组小鼠IRE1和促凋亡基因半胱氨酸蛋白酶-3(Caspase-3)的蛋白表达量变化.结果:与对照组相比,热应激组的血清睾酮含量显著下降(P<0.01),睾丸组织中IRE1和Caspase-3蛋白表达量显著增加(P<0.01,P<0.01);与热应激组相比,α-硫辛酸+热应激处理组的血清睾酮含量显著升高(P<0.05),在睾丸生精小管和间质细胞中均可观察到IRE1蛋白的阳性免疫染色,但IRE1蛋白阳性细胞数量显著减少(P<0.05),IRE1和Caspase-3的蛋白表达量均显著降低(P<0.05,P<0.05).结论:热应激能够抑制小鼠睾丸睾酮的分泌,降低血清睾酮的含量;在本试验条件下,添加60 mg/(kg·d)的α-硫辛酸能够有效增加热应激状态下小鼠的血清睾酮含量,其发挥保护作用的机制可能与α-硫辛酸抑制IRE1介导的非折叠蛋白反应信号通路激活、降低凋亡促进基因Caspase-3的蛋白表达量有关.     

HPLC法测定西洋参类保健食品中人参皂苷成分的含量

目的建立HPLC法测定以西洋参为主要原料的保健食品中人参皂苷成分含量的方法。方法采用高效液相色谱法测定。色谱柱:岛津C18柱,流动相:乙腈-水(梯度),流速:1.0mL/min,检测波长:203nm。结果人参皂苷Rg1在36.18～361.8ng(r=0.999),人参皂苷Re在0.2254～2.254μg(r=0.9999),人参皂苷Rb1在0.67498～6.7498μg(r=0.9999)之间线性关系良好;人参皂苷Rg1的平均回收率为99.3%,RSD=4.62%;人参皂苷Re的平均回收率101.7%,RSD=1.63%;人参皂苷Rb1的平均回收率100.3%,RSD=1.49%。结论试验表明,该方法操作简单,分离效果好,灵敏度高,可以用于以西洋参为主要原料的保健食品的质量控制。     

人参皂苷和三七皂苷五种成分神经保护作用的均匀设计-高通量筛选研究

目的:通过对人参皂苷和三七皂苷多成分多水平均匀设计配伍的神经保护作用筛选研究,评价中药有效成分的均匀设计-高通量筛选技术。方法:选取人参皂苷Re,Rb1,Rg1,Rg3和三七皂苷R1等五种皂苷单体6个水平(1×10-4~1×10-9mol.L-1)进行均匀设计配伍组合,通过神经细胞血清剥夺损伤模型进行药效高通量筛选;得到的最佳组合样品,再通过小鼠脑缺血再灌注损伤模型(避暗法、断头耐缺氧实验)及血清和脑、心肌组织老化相关酶测定,进行药效学评价。结果:在细胞实验中筛选得到的最佳3个组合样品(A11,A12,P5),药效(细胞存活率>90%)高于1×10-4mol.L-1浓度的五种皂苷单体及维生素E(细胞存活率最高78%);可明显改善小鼠脑缺血再灌注损伤所致的记忆障碍,增强耐缺氧能力,提高组织超氧化物歧化酶(superoxide dismutase,SOD)活性,降低一氧化氮(nitric oxide,NO)含量,维持谷丙转氨酶(glutamic-pyruvic transaminase,ALT)及乳酸脱氢酶(lactic dehydrogenase,LDH)含量稳定(P<0.01~0.05)。结论:均匀设计配伍与...     

人参皂苷对衰老大鼠学习记忆和脑单胺类神经递质的影响

目的:观察人参皂苷对D-半乳糖(D-gal)致衰老大鼠学习记忆和脑单胺类神经递质的影响。方法:成年雄性SD大鼠随机分为正常组,衰老组,人参皂苷低(50 mg/kg)、高剂量组(100 mg/kg),每组10只,制备D-gal亚急性衰老大鼠模型,采用自主活动仪记录法、Morris水迷宫法、穿梭箱法检测各组大鼠的自主活动和空间学习记忆能力;采用高效液相色谱-电化学法检测各组大鼠海马、下丘脑单胺类神经递质去甲肾上腺素(NE)、多巴胺(DA)、5-羟色胺(5-HT)含量。结果:与正常组比较,模型组干预后大鼠自主活动次数显著减少(P<0.01),大鼠水迷宫探索路径、搜台潜伏期、平均潜伏期、进入错误区及电击时间延长(P<0.01),遭受电击次数显著增加(P<0.01),海马及下丘脑NE、DA、5-HT含量均显著降低(P<0.01)。与模型组比较,人参皂苷低、高剂量组大鼠自主活动次数明显增加(P<0.05,P<0.01),探索路径和搜台潜伏期、平均潜伏期、进入错误区及电击时间显著缩短(P<0.05,P<0.01),遭受电击次数明显减少(P<0.05,P<0.01),海马及下丘脑NE、DA、5-HT含量均明显升高。结论:人参皂苷具有改善衰老大鼠的空间记忆能力,提高大鼠脑组织中单胺类神经递质含量,进而延缓脑衰老进程的作用。     

复方血栓通中多药配伍对君药三七有效成分药代动力学的影响（英文）

目的:通过比较君药三七和复方血栓通中有效成分的药代动力学,为复方血栓通的配伍和组方寻找科学依据。创新点:首次为复方血栓通的组方合理性提供一定的科学依据。方法:研究采用实验室前期建立的液相色谱-质联用方法同时测定大鼠血浆中的三七皂苷R1(NR1)、人参皂苷Rg1(GRg1)和人参皂苷Rb1(GRb1),对灌胃给予三七和复方血栓通胶囊后大鼠血浆中NR1、GRg1和GRb1的药代动力学参数进行测定。结论:复方血栓通胶囊中除三七外的其他三味药的成分可以增加三七中NR1、GRg1和GRb1在大鼠体内的暴露水平,一定程度上揭示了复方血栓通全方配伍的合理性。     

七龙天胶囊质量标准实验研究

采用薄层色谱法(TLC)对七龙天胶囊中的地龙进行定性鉴别,结果表明,地龙对照药材在与供试品的薄层色谱相应位置上,有相同颜色斑点,阴性对照无干扰.另采用高效液相色谱法(HPLC)测定处方中三七皂苷R1、人参皂苷Rg1和Rb1及红景天苷的质量分数,结果显示,三七皂苷R1在0.178~3.560μg、人参皂苷Rb1在0.430~8.600μg、人参皂苷Rg1在0.539~10.780μg、红景天苷在0.206~4.120μg范围内与峰面积值呈良好线性关系(r分别为0.999 7,0.999 8,0.999 7,1.000 0,n=6).平均加样回收分别为97.82%(RSD=1.28%),97.92%(RSD=1.62%),97.07%(RSD=0.82%),96.58%(RSD=1.45%).TLC法及HPLC法操作简便、准确、重复性好,可对七龙天胶囊进行质量控制.     

Reducing the oxidative stress mediates the cardioprotection of bicyclol against ischemia-reperfusion injury in rats

Objective

To investigate the beneficial effect of bicyclol on rat hearts subjected to ischemia-reperfusion (IR) injuries and its possible mechanism.

Methods

Male Sprague-Dawley rats were intragastrically administered with bicyclol (25, 50 or 100 mg/(kg·d)) for 3 d. Myocardial IR was produced by occlusion of the coronary artery for 1 h and reperfusion for 3 h. Left ventricular hemodynamics was continuously monitored. At the end of reperfusion, myocardial infarct was measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining, and serum lactate dehydrogenase (LDH) level and myocardial superoxide dismutase (SOD) activity were determined by spectrophotometry. Isolated ventricular myocytes from adult rats were exposed to 60 min anoxia and 30 min reoxygenation to simulate IR injuries. After reperfusion, cell viability was determined with trypan blue; reactive oxygen species (ROS) and mitochondrial membrane potential of the cardiomyocytes were measured with the fluorescent probe. The mitochondrial permeability transition pore (mPTP) opening induced by Ca²⁺ (200 μmol/L) was measured with the absorbance at 520 nm in the isolated myocardial mitochondria.

Results

Low dose of bicyclol (25 mg/(kg·d)) had no significant improving effect on all cardiac parameters, whereas pretreatment with high bicyclol markedly reduced the myocardial infarct and improved the left ventricular contractility in the myocardium exposed to IR (P<0.05). Medium dose of bicyclol (50 mg/(kg·d)) markedly improved the myocardial contractility, left ventricular myocyte viability, and SOD activity, as well decreased infarct size, serum LDH level, ROS production, and mitochondrial membrane potential in rat myocardium exposed to IR. The reduction of ventricular myocyte viability in IR group was inhibited by pretreatment with 50 and 100 mg/(kg·d) bicyclol (P<0.05 vs. IR), but not by 25 mg/(kg·d) bicyclol. The opening of mPTP evoked by Ca²⁺ was significantly inhibited by medium bicyclol.

Conclusions

Bicyclol exerts cardioprotection against IR injury, at least, via reducing oxidative stress and its subsequent mPTP opening.     

运动对糖尿病诱导的大鼠海马氧化应激的影响

背景:氧化应激形成诱导多细胞通路的基础,其能导致糖尿病并发症,最能导致身体虚弱的疾病——是神经系统疾病. 研究的目的是评价跑台运动是否能减轻链脲霉素诱导的糖尿病大鼠海马氧化应激和细胞凋亡率.方法:40只雄性Wistar大鼠随机分为4组,每组10只,即对照组、运动组、糖尿病组和糖尿病运动组,通过给大鼠注射链脲霉素诱导糖尿病模型. 所有运动组大鼠在动物电动跑台上进行8周运动,在8周末,大鼠海马在冰冻中立即分离并冷冻保存. 收集上清液于-80°C保存,用于测定抗氧化酶和TBARs,用ELISA试剂盒检测细胞死亡检测细胞凋亡指数. 结果:糖尿病不运动组和糖尿病运动组的TBARs水平显著高于对照组;运动组SOD和GPx显著增高,糖尿病不运动组显著降低;与对照组相比,糖尿病不运动组CAT活性显著降低;与对照组相比,糖尿病不运动组细胞凋亡率显著增加,运动组显著降低. 结论:运动对糖尿病大鼠产生有益影响,部分原因可能是因为运动诱导氧化应激适应能力的改变.     

HPLC监测的人参皂甙在温和酸性条件下的降解变化

对人参皂甙20(s)-原人参二醇组中的两种主要单体皂甙Rd与Rb_1在近似胃液条件下的酸水解情况以HPLC法进行了分析检测,结果表明:人参皂甙Rd降解产生次级甙20(s)一Rg_3和F_2;Rb_1降解产生次级甙20(s)-Rg_3、F_2和Rd.综合这些研究,文中对该条件下皂甙甙键的裂解顺序、次级甙的衍生规律以及水解相关因素的影响亦做了初步探讨与归纳。     

Optimal time for mesenchymal stem cell transplantation in rats with myocardial infarction

Background:Bone marrow mesenehymal stem cell(MSC)transplantation is a promising strategy in the treatment of myocardial infarction(MI).However,the time for transplanting cells remains controversial.The aim of this study was to find an optimal time point for cell transplantation.Methods:MSCs were isolated and cultured from Sprague-Dawley(SD) rats.MI model was set up in SD rats by permanent ligation of left anterior descending coronary artery.MSCs were directly injected into the infarct berder zone at 1 h,1 week and 2 weeks after MI,respectively.Sham-operated and MI centrel groups received equal volume of phosphate buffered saline(PBS).At 4 weeks after MI,cardiac function Was assessed by echocardiography;vessel density Was analyzed on hematoxylin-eosin stained slides by light microscopy;the apoptosis of cardiomyocytes Was evaluated by terminal deoxynucleotidy1 transferase-mediated dUTP nick end-labeling(TUNEL) assay;the expressions of proteins were analyzed by Western blot.Results:MSC transplantation improved cardiac function.reduced the apoptosis of cardiomyocytes and increased vessel density.These benefits were more obvious in l-week group than in 1-h and 2-week groups.There are more obvious increases in the ratio of bc1-2/bax and the expression of vascular endothelial growth factor(VEGF)and more obvious decreases in the expression of cleaved-caspase-3 in 1-week group than those in other two groups.Conclusion:MSC transplantation was beneficial for the recovery of cardiac function.MSC transplantation at l week post-MI exerted the best effects on increases of cardiac function,anti-apoptosis and angiogenesis.     

Developing a rat model of dilated cardiomyopathy with improved survival

To compare the continuous infusion and intermittent bolus injection administration protocols of doxorubicin (Dox) under the same cumulative dose (12 mg/kg), and establish a rat dilated cardiomyopathy model with improved survival, a total of 150 Sprague-Dawley (SD) rats were divided into three groups: a control group, administered with normal saline; a Dox 1 group, administration twice a week at 1 mg/kg; a Dox 2, administration once a week at 2 mg/kg. Mortality rates in the Dox 1 and Dox 2 groups were 22% and 48%, respectively (P<0.05). As shown by echocardiography, both Dox groups exhibited significant chamber dilatation and reduced cardiac function (all P<0.05 vs. control). Plasma brain natriuretic peptide and C-reactive protein concentrations were significantly increased (P<0.05) with both Dox regimens. The concentrations of Caspase-3 in myocardial tissues of rats significantly increased in both doxorubicin regimens. Myocardial metabolism imaging by histology and ¹⁸F-fluoro-deoxyglucose-positron emission tomography (¹⁸FDG-PET) both revealed decreased myocardial viability and necrosis, and even interstitial fibrosis, in left ventricles (LVs) in both Dox groups. Serum creatinine and aspartate aminotransferase concentrations were significantly higher in the Dox 2 model than in the Dox 1 model. Doxorubicin given at both regimens induced dilated cardiomyopathy, while its administration at lower doses with more frequent infusions reduced the mortality rate.     

Simultaneous determination of saponins in Radix Glycyrrhizae, Notoginseng and Ginseng by high performance liquid chromatography

To establish a method for determining five saponins（notoginsenoside R1, ginsenoside Rg1, ginsenoside Re, ginsenoside Rb1 and ammonium glycyrrhizinate） in Glycyrrhizae, Notoginseng and Ginseng, the high performance liquid chromatography with diode array detector（HPLC-DAD） method was applied to an Inertsil ODS-SP column（4.6 mm×250 mm, 5 μm） with a mobile phase consisting of acetonitrile-0.05% phosphoric acid in a gradient elution manner. The flow rate was 1.0 mL/min. The column temperature was 30 ℃ and the detection wavelengths were 203 nm and 237 nm, respectively. The linear ranges were 0.700,0—7.000,0 μg for R1（r=1.000,0）, 0.751,1— 7.511,4 μg for Rg1（r=1.000,0）, 0.677,2—6.771,6 μg for Re（r=1.000,0）, 0.733,9—7.339,1 μg for Rb1（r= 1.000,0）, and 0.540,0—5.399,8 μg for ammonium glycyrrhizinate（r=0.999,9）, respectively. In addition, their average recoveries were 100.28%, 105.83%, 104.09%, 99.36% and 98.54%, respectively. The relative standard deviations（RSDs） of precision, reproducibility and recovery were all less than 1.5%. The results indicate that the method is simple, accurate and reproducible so that it can be used for the simultaneous determination of the five saponins in Chinese patent medicines containing the three kinds of herbs.     

Effect of compatible herbs on the pharmacokinetics of effective components of <Emphasis Type="Italic">Panax notoginseng</Emphasis> in Fufang Xueshuantong Capsule

Fufang Xueshuantong (FXT) is a well-known Chinese herbal formula which has been used to treat cardiovascular and ophthalmic diseases, especially diabetic retinopathy. Panax notoginseng (Burkill) F.H. Chen (PN) is the main herb of FXT, whose major bioactive constituents are ginsenosides. However, the scientific basis of the compatibility of FXT is still ambiguous. The present study investigated the scientific basis of the compatibility of FXT by comparing the pharmacokinetics of marker compounds after oral administrations of PN and FXT. A high performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) method was developed for simultaneous detection of notoginsenoside R1 (NR1), ginsenoside Rg1 (GRg1), and ginsenoside Rb1 (GRb1) in rat plasma. The pharmacokinetic studies of FXT and PN were performed using the established method with the pharmacokinetic parameters being determined by non-compartmental analysis. The results showed that the pharmacokinetic parameters (maximum concentration, area under the curve (AUC_0–t ), clearance, and mean residence time) of NR1, GRg1, and GRb1 were significantly different after oral administration of FXT (P<0.05) compared with PN. The AUC_0–t values of GRg1 and GRb1 were 1.7- and 3.4-fold greater, respectively, in FXT than in PN. The compatible herbs of FXT could prolong the retention time and increase the systemic exposure of NR1, GRg1, and GRb1 compared with PN in vivo, providing some scientific basis for the compatibility and clinical use of FXT.     

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…