褪黑素对大鼠梗阻性黄疸肾损害的保护作用

目的　探讨一氧化氮 (NO)在大鼠梗阻性黄疸肾功能损害发生中的作用 ,以及褪黑素 (melatonin ,Mel)的保护作用。方法　 6 4只雄性SD大鼠随机均分为 4组 :正常对照组 (CN组 )、假手术组 (SO组 )、胆总管结扎组(BLD组 )和褪黑素治疗组 (BDL +Mel组 )。应用胆总管结扎法建立梗阻性黄疸模型 ,分别于手术后第 4天和第 8天两个时间点检测 4组中血浆NO、TB、DB、ALT、AST、BUN、Cr水平以及肾组织中NO水平和iNOS活性 ;光镜下观察肾组织病理形态改变。结果　BDL组大鼠血浆NO、TB、DB、ALT、AST、BUN、Cr水平和肾组织NO水平及iNOS活性明显升高 (P<0 .0 1) ,褪黑素治疗可使血浆NO、ALT、AST、BUN及Cr水平和肾组织中NO水平及iNOS活性显著降低 ,与BDL组比较差异有显著性意义 (P<0 .0 1)。结论　梗阻性黄疸时 ,肾组织iNOS活性增强 ,NO大量产生参与了肾功能损害的发生、发展 ;褪黑素对大鼠梗阻性黄疸肾损害的保护作用至少部分是通过干扰NO通路实现的。     

精氨酸对梗阻性黄疸大鼠肝损伤的保护作用及其对肝细胞凋亡的影响

目的 探讨梗阻性黄疸时精氨酸是否对肝脏具有保护作用及其对肝细胞凋亡的影响.方法 Wistar大鼠42只随机分为3组:A组为假手术组、B组为梗阻性黄疸组、C组为精氨酸治疗组;B组和C组采取双重结扎大鼠胆总管制作梗阻性黄疸模型,C组术后第1天开始每天腹腔注射精氨酸500 mg/(kg·d),分别于术后第7天和第14天取材,采集鼠血清检测TBIL、DBIL、ALT、AST;大鼠肝脏组织进行HE染色切片观察组织形态,电镜观察胞内形态并对组织切片应用Bax、Bcl-2试剂盒行免疫组化染色.结果 与A组大鼠相比,B组大鼠血清胆红素和转氨酶明显增高.肝细胞损伤不断加重并出现显著凋亡改变,随着胆总管结扎时间的延长而更加明显.应用精氨酸治疗的C组大鼠,其肝功能和肝脏组织病理学改变较B组轻.B组和C组大鼠肝组织中Bax、Bcl-2蛋白表达均随时间而增多,但B组Bax表达增多较明显,而C组Bcl-2蛋白表达增多较明显.结论 精氨酸对梗阻性黄疸大鼠肝脏有保护作用,可能是通过上调肝脏组织Bcl-2蛋白表达,下调肝脏组织Bax蛋白的表达减少细胞凋亡来实现的.     

青藤碱对梗阻性黄疸大鼠肝损伤保护作用研究

目的:探讨青藤碱对梗阻性黄疸大鼠肝脏损伤的保护作用。方法:将32只大鼠随机均分为假手术组,模型组和高、低2个剂量青藤碱干预组。除假手术组外,其余各组大鼠均行胆总管结扎。术后第1天开始,2个青藤碱干预组大鼠分别给予40 mg/kg和80 mg/kg青藤碱灌胃,假手术组和模型组给予等体积的生理盐水灌胃,1次/d。第8天处死各组大鼠,取腹主动脉血测血清总胆红素(TBIL),直接胆红素(DBIL),谷丙转氨酶(AST),谷草转氨酶(ALT)水平,取右肝用试剂盒测肝组织中丙二醛(MDA),髓过氧化物酶(MPO)含量,总抗氧化能力(T-AOC),实时荧光定量PCR法测转化生长因子β1(TGF-β1)mRNA的表达,取左肝做HE和免疫组织化学染色分别检测肝组织病理学和TGF-β1蛋白的表达。结果:除假手术组外,各组大鼠肝组织均出现不同程度的病理改变,其中2个青藤碱干预组大鼠肝组织病变明显轻于模型组。与假手术组比较,各组大鼠血清TBIL,DBIL,ALT,AST水平明显增高;肝组织MDA,MPO含量明显升高,T-AOC明显降低;肝组织TGF-β1的蛋白和基因表达明显增高(均P<0.05)。模型组上述指标的变化程度均较2个青藤碱干预组明显(均P<0.05),而高低2个青藤碱干预组间上述指标均无统计学差异(均P>0.05)。结论:青藤碱对梗阻性黄疸大鼠肝脏的损伤具有保护作用,其机制可能与降低TGF-β1的表达有关。     

氢生理盐水对梗阻性黄疸大鼠肝功能的保护作用

目的研究氢生理盐水对梗阻性黄疸大鼠肝功能的保护作用并探讨其可能机制。方法将雄性SD大鼠随机分为3组(n=14),除假手术组外,均采用双重结扎胆总管造成阻黄模型,不同组大鼠分别给予等量生理盐水和氢生理盐水(5ml/kg,i.p.),10天后检测血清肝功能、内毒素及HMGB1水平,肝组织MDA、HMGB1、TNF-α、IL-1β、IL-6含量及MPO活性,并用光镜观察肝细胞变性、死亡和炎细胞浸润情况。结果胆总管结扎后,对照组大鼠肝功能水平明显降低,血清内毒素、HMGB1及肝组织MDA、HMGB1、TNF-α、IL-1β、IL-6含量及MPO活性明显升高,光镜下肝细胞大量变性坏死伴炎性细胞浸润。氢生理盐水治疗组大鼠肝功能显著好转,各指标明显低于对照组(P0.01)。结论氢生理盐水能显著减轻梗阻性黄疸大鼠肝损伤,并能有效抑制氧化应激及炎性反应。     

氨基胍对梗阻性黄疸大鼠治疗作用的实验研究

目的 探讨诱导型一氧化氮合酶(iNOS)抑制剂氨基胍(AG)对梗阻性黄疸大鼠的治疗作用及作用机制.方法 雄性Wistar大鼠40只,随机分为正常对照组、假手术组、黄疸组、氨基胍治疗组4组,每组10只.通过测定治疗前后肝功、血胆红素、内毒素、乳酸、肝组织丙二醛水平,以及通过对肝脏、小肠的形态学分析来探讨氨基胍对梗阻性黄疽大鼠的治疗作用.结果 血浆内毒素和血清乳酸、肝组织丙二醛随着胆道梗阻时间的延长逐步升高,并伴随着肝脏小肠病理形态学的改变.氨基胍治疗组各项指标显著低于对照组,并能改善肝组织及小肠病理形态.结论 氨基胍(AG)可通过减轻脂质过氧化与内毒素血症发挥保护肝脏及小肠的作用,为治疗梗阻性黄疸患者提供了一种新的思路和方法.

Abstract：

Objective To evaluate the therapeutic effect and mechanism of specific inducible nitric oxide synthase(iNOS)aminoguanidine(AG)in rats with obstructive jaundice.Methods Forty male Wistar rats were divided randomly into four groups: normal control group, sham operation group, obstructive jaundice group and aminoguanidine therapeutic group.Each group had 10 rats.We assayed levels of liver function,hemobilirubin, endotoxin,lactic acid and malondialdehyde before and after therapy, and we also analyzed pathology of the liver and small intestine.Then we could explore the therapeutic effect of AG in rats with obstructive jaundice.Results The levels of endotoxin,lactic acid and malondialdehyde in blood increased progressively along with the pathological changes of the liver and small intestine.Each of the AG group parameters was significantly lower, and the pathological changes of liver and small intestine were improved.Conclusion AG could protect liver and small intestine by attenuating lipid peroxidative and endotoxemia,and provide a new way to cure obstructive jaundice.     

梗阻性黄疸大鼠肝细胞凋亡分析及硒的保护作用

目的 研究梗阻性黄疸（梗黄）大鼠肝脏细胞凋亡的发生发展规律及其机制，以及硒的抗凋亡作用。方法 使用生化和末端脱氧核甘酸介导生物素标记（TUNEL）技术测量不同组别，不同梗黄时间大鼠肝脏的谷胱甘肽过氧化物酶（GPx)活性，活性氧（ROS）水平及凋亡指数（AI），并进行多元分析，结果 胆总管结扎3d后，凋亡细胞开始出现，7d时显著增多，均11d达高峰，14d时有所减少。单纯梗黄组（OJ）ROS水平随时间延长而持续升高，GPx活性则进行性下降，AI与ROS水平变化呈正相关（r=0.95)，于11d时达高峰。硒治疗组呈现相似变化，但各时相点上GPx活性均高于OJ组（P＜0．05）。ROS水平和AI则相反（P＜0．05）。结果表明，ROS促进凋亡的作用最为明显，胆红素和胆汁酸次之。GPx 则表现出显著的凋亡拮抗作用。结论 ROS是梗黄大鼠肝脏细胞凋恨的重要因素。硒对肝细胞凋亡有明显保护作用。     

黄芪对梗阻性黄疸大鼠肾功能的保护作用

目的:探讨黄芪对梗阻性黄疸大鼠肾功能的保护作用及机理.方法:SD大鼠胆总管结扎后分2组,每组20只,术后分别用3 mL黄芪或生理盐水腹腔注射.假手术组20只.术后10 d、20 d(每小组n=10)心脏取血测定血浆内皮素(ET-1)、血清超氧化物歧化酶(SOD)和丙二醛(MDA)含量,同时测定血清肌酐(Cr)尿素氮(BUN)和直接胆红素(DB),对肾脏行病理形态学观察.结果:血浆ET-1、血清MDA浓度在梗阻10 d即升高且随胆道梗阻时间延长进一步升高,SOD在梗阻10 d即下降,同时伴有血清Cr、BUN、DB的升高和肾脏病理形态学的进行性改变.黄芪治疗组ET-1及MDA显著低于对照组,而SOD显著高于对照组,并能改善肾组织病理形态.结论:大鼠梗阻性黄疸时血浆ET-1升高及氧自由基损害是肾损伤的原因,黄芪通过降低ET-1水平、抗氧化作用对梗阻性黄疸大鼠肾脏起保护作用.     

黄芪对梗阻性黄疸大鼠肝功能的保护作用

目的:探讨黄芪注射液对实验性梗阻性黄疸大鼠肝功能的保护作用及作用机理.方法:SD大鼠行胆总管结扎后分别用3 mL黄芪注射液或生理盐水腹腔注射.术后测定血浆内皮素(ET-1)、血清超氧化物歧化酶(SOD)、丙二醛(MDA)含量,同时测定谷丙转氨酶(AST)、直接胆红素(DB)和总胆汁酸(TBA)浓度,并对肝脏行光镜下病理形态学观察.结果:血浆ET-1、血清MDA浓度在梗阻10 d即升高,随胆道梗阻时间延长进一步升高,SOD在梗阻10 d即下降,同时伴有血清AST、DB和TBA的升高和肝脏病理形态学的进行性改变.黄芪治疗组ET-1及MDA显著低于对照组,而SOD显著高于对照组,并能改善肝组织病理形态.结论:大鼠梗阻性黄疸时,血浆ET-1水平升高及氧自由基损害可能是肝损伤的原因,黄芪通过降低ET-1水平、抗氧化作用对梗阻性黄疸大鼠的肝脏起保护作用.     

茶油对梗阻性黄疸心脏保护作用的实验研究

目的：探讨富含单不饱和脂肪酸的茶油梗阻性黄疸大鼠的心脏保护作用。方法制备大鼠梗阻性黄疸模型，运用血清酶现理组织学和形态定量学方法研究喂饲茶油对心肌细胞形态和功能的作用。结果茶油能明显改善梗阻性黄疸大鼠营养状况，明显降低血清总胆红素（ＴＢ）、直接胆红素（ＤＢ）、谷丙转氨酶（ＧＰＴ）和谷草转氨酶（ＧＯＴ）的水平；增强心肌细胞线粒体内琥珀酸脱氢酶（ＳＤＨ）的活性；在一定程度上保持心肌细胞线粒体膜、核膜和     

氨基胍对梗阻性黄疸大鼠治疗作用的实验研究

目的 探讨诱导型一氧化氮合酶(iNOS)抑制剂氨基胍(AG)对梗阻性黄疸大鼠的治疗作用及作用机制.方法 雄性Wistar大鼠40只,随机分为正常对照组、假手术组、黄疸组、氨基胍治疗组4组,每组10只.通过测定治疗前后肝功、血胆红素、内毒素、乳酸、肝组织丙二醛水平,以及通过对肝脏、小肠的形态学分析来探讨氨基胍对梗阻性黄疽大鼠的治疗作用.结果 血浆内毒素和血清乳酸、肝组织丙二醛随着胆道梗阻时间的延长逐步升高,并伴随着肝脏小肠病理形态学的改变.氨基胍治疗组各项指标显著低于对照组,并能改善肝组织及小肠病理形态.结论 氨基胍(AG)可通过减轻脂质过氧化与内毒素血症发挥保护肝脏及小肠的作用,为治疗梗阻性黄疸患者提供了一种新的思路和方法.     

川芎嗪对大鼠肝脏缺血-再灌注损伤保护作用的机理研究

目的　研究川芎嗪注射液对大鼠肝脏缺血再灌注损伤的保护作用。方法　96 只SD大鼠被随机均分为假手术组、肝脏缺血再灌注组(I/R组)和肝脏缺血+川芎嗪再灌注组(简称治疗组)3 组,分别于术前及术后30 min、6 h及24 h检测血浆丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)及乳酸脱氢酶(LDH),观察每组大鼠1周存活情况及肝脏病理组织学变化,并行肝细胞凋亡指数检测。结果　治疗组术后1 周大鼠存活情况好于I/R组(P<0.05); 治疗组及I/R组血浆ALT、AST及LDH均明显高于假手术组(P<0.05),但治疗组低于I/R组(P<0.05)。光镜下见,缺血再灌注后肝血窦和中央静脉明显瘀血,肝细胞坏死I/R组重于治疗组。肝细胞凋亡指数I/R组高于治疗组(P<0.05)。结论　川芎嗪对大鼠肝脏缺血再灌注损伤具有明显的保护作用。     

缺血预处理对大鼠移植肝脏缺血再灌注损伤的保护作用

目的　探讨缺血预处理 (ischemicpreconditioning ,IP)对大鼠移植肝脏缺血再灌注损伤的保护作用。 方法　采用SD大鼠原位肝移植动物模型 ,供肝冷保存时间 10 0min ,无肝期 2 5min。 64只SD大鼠随机均分成两组 :对照组 ,获取供肝前仅以肝素生理盐水经门静脉灌注 ;IP组 ,获取供肝前阻断肝门血供 10min ,再灌注 10min ,然后再以肝素生理盐水经门静脉灌注。每组受体的一半 (n =8)用于观察存活率 ,另一半 (n =8)用于移植肝脏再灌注 2h后取血及肝脏检测。结果　IP组的 1w存活率、胆汁分泌量、抗氧化酶活力、血清NO水平均明显高于对照组 (P<0 .0 5 ) ,血清ALT、AST、LDH、TNF及肝组织中的过氧化产物含量均明显低于对照组 (P<0 .0 5 ) ,组织的病理改变也轻于对照组。结论　IP能够提高血清NO水平 ,降低血清TNF含量 ,对大鼠移植肝脏的缺血再灌注损伤具有保护作用     

缺血预处理对大鼠肝脏低温保存损伤的保护作用

目的　探讨缺血预处理 (IPC)对大鼠肝脏低温保存损伤的保护作用。方法　制备大鼠肝脏离体非循环灌注模型 ,对供肝分别作不同时间的IPC (IPC1组缺血 5min、IPC2 组缺血 10min、IPC3 组缺血 15min) ,而后比较各组供肝的损伤程度。结果　流出液中AST和ALT的水平 ,IPC1组分别为 (4 0 .1± 6.3 )U/L和 (17.1± 0 .5 )U /L ,IPC2 组分别为 (5 3 .6± 3 .7)U/L和 (19.7± 0 .5 )U /L ,均显著低于未预处理 (NPC)组的 (64 .5± 8.2 )U/L和 (2 3 .8± 3 .9)U /L (P<0 .0 5 ) ;IPC1组又显著低于IPC2 组和IPC3 组的 (63 .8± 7.2 )U/L和 (2 2 .8± 2 .5 )U /L (P<0 .0 5 )。LDH水平 ,NPC组、IPC1组、IPC2 组和IPC3 组分别为 (10 4.3± 2 0 .6)U/L、(84.1± 19.7)U /L、(90 .5± 2 1.1)U/L和 (10 3 .1± 18.5 )U /L ,4组间差异无统计学意义 (P>0 .0 5 ) ,但均高于正常组〔(71.5± 18.9)U /L〕 (P<0 .0 5 )。胆汁分泌量及肝组织ATP含量 ,IPC1组分别为 (5 3 .5± 10 .2 ) μl和 (6.15± 0 .65 ) μmol/g ,IPC2 组分别为 (4 1.5± 8.1) μl和 (4 .77± 0 .2 1) μmol/g ,均显著高于NPC组的 (2 2 .8± 9.7) μl和 (2 .62± 0 .3 4) μmol/g (P<0 .0 5 ) ;IPC1组又显著高于IPC2 组和IPC3 组的 (2 7.5± 2 .8) μl和 (2 .61     

Neuroprotective Effect of Melatonin on Cortical Impact Injury in the Rat

Summary  The pineal hormone melatonin is a highly efficient physiological scavenger of free radicals involved in secondary brain damage. A variety of experimental studies have demonstrated a neuroprotective effect for melatonin, based on its antioxidant activity. The purpose of the present study was to investigate the time-dependency and a possible protective effect of exogenous melatonin in the cortical impact model in rats. The protective effect was quantified determining contusion volume, brain edema and brain water content.  45 anesthetized male Sprague-Dawley rats (250–350 mg) were subjected to cortical impact injury of moderate severity (7 m/s, deformation 2 mm). Melatonin (100 mg/kg bw i.p.), or a vehicle was injected 20 min before trauma, immediately after, and 1 and 2 hours after trauma during daytime and nighttime. Posttraumatic lesion volume using hematoxylin-eosin staining, hemispheric swelling, brain water content, cerebral perfusion pressure and intracranial pressure 24 hours after injury were investigated.  Melatonin, given during nighttime, significantly reduced contusion volume corresponding to a mean reduction of contusion volume of 27% (placebo, n=7: 41.9±5.2 mm³, melatonin, n=8: 30.5±4.2 mm³, p<0.05). Given during daytime, the reduction in contusion volume was not significant (placebo, n=8: 42.1±5.1 mm³, melatonin, n=8: 35.9±2.2 mm³, reduction of 15%, p=0.08, n.s.). Hemispheric swelling was unchanged by melatonin treatment. Mean arterial blood pressure and rectal temperature remained stable before and after the cortical impact injury and injection of melatonin. This study shows that melatonin significantly reduces contusion volume with major effects during night.     

Protective Effect of Melatonin Against Ischemia/Reperfusion-Induced Oxidative Remote Organ Injury in the Rat

Purpose Oxygen free radicals are considered to be important components involved in the pathophysiological tissue alterations observed during ischemia/reperfusion (I/R). Based on the potent antioxidant effects of melatonin, we investigated the putative protective role of melatonin against I/R-induced oxidative remote organ injury.Methods Wistar albino rats were subjected to 1 h of infrarenal aortic occlusion followed by 1 h of reperfusion to induce I/R damage. Melatonin (10 mg/kg, s.c.) or vehicle was administered twice, 15 min prior to ischemia and immediately before the reperfusion period (I/R + Mel or I/R groups). At the end of the reperfusion periods, the rats were decapitated and hepatic, ileal, and lung tissue samples were removed for biochemical analyses of: malondialdehyde (MDA), an end product of lipid peroxidation; the glutathione (GSH) levels, a key antioxidant; and the myeloperoxidase (MPO) activity, as an indirect index of neutrophil infiltration. The serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were measured to evaluate the liver function. The wet/dry lung weight ratio was calculated to determine the extent of lung damage.Results The results revealed the occurrence of I/R-induced oxidative organ damage, as evidenced by increases in the MDA and MPO activity, and a decrease in GSH. Furthermore the AST, ALT levels, and the wet/dry lung weight ratio, which all increased due to I/R, were all observed to decrease after melationin treatment.Conclusion Since melatonin administration reversed these oxidant responses, it seems likely that melationin has a protective effect against oxidative organ damage induced by I/R.     

参附注射液对大鼠肢体缺血再灌注后肝脏损伤的保护作用

目的观察参附注射液对大鼠肢体缺血再灌注损伤后肝功能、血红素加氧酶-1（HO-1）表达的影响,并对其保护机制做一初步探讨。方法 64只清洁级SD雄性大鼠,用随机数字表法随机分为4组,每组16只,分别为假手术组、缺血再灌注组、参附干预组、参附＋锌原卟啉Ⅸ（Znpp）干预组。假手术组：大鼠麻醉后仅分离不夹闭股动脉,分离血管前10 min以7.5 mL/kg腹腔注射生理盐水;缺血再灌注组：夹闭股动脉前10 min以7.5 mL/kg腹腔注射生理盐水,夹闭股动脉缺血3 h,再灌注4 h;参附干预组：夹闭股动脉前10 min以7.5 mL/kg腹腔注射参附注射液,夹闭股动脉缺血3 h,再灌注4 h;参附＋Znpp干预组：术前30 min腹腔注射Znpp 5 mg/kg,余同参附干预组。再灌注完毕后取材,取外周静脉血测血清谷丙转氨酶（GPT）、谷草转氨酶（GOT）含量;取肝组织测定肝组织中丙二醛（MDA）含量、超氧化物歧化酶（SOD）活性;采用免疫组织化学法测定肝脏组织中HO-1蛋白表达;光镜下观察肝脏病理学改变。结果 1与假手术组比较,各肢体缺血再灌注造模组MDA含量均明显升高（P〈0.05）,SOD活性明显降低（除参附干预组外,P〈0.05）,GPT、GOT含量均明显升高（P〈0.05）,HO-1蛋白表达明显升高（P〈0.05）。2与缺血再灌注组比较,参附干预组MDA含量明显降低（P〈0.05）,SOD活性明显升高（P〈0.05）,血清GPT、GOT含量明显降低（P〈0.05）,肝组织中HO-1蛋白表达升高（P〈0.05）。3与参附干预组比较,参附＋Znpp干预组MDA含量明显升高（P〈0.05）,SOD活性明显降低（P〈0.05）,血清GPT、GOT含量明显升高（P〈0.05）,而肝组织HO-1蛋白表达差异无统计学意义（P〉0.05）。结论肢体缺血再灌注可造成肝脏功能损伤,给予参附注射液预处理可以减轻肝脏损害程度,这种保护作用可能与参附注射液预处理上调HO-1蛋白在肝组织中的表达、抑制氧自由基生成?     

前列地尔对兔肝缺血再灌注时肝细胞凋亡的保护作用

目的 探讨前列地尔对兔肝脏缺血再灌注损伤时,有效减少肝细胞凋亡的机制.方法 将健康新西兰兔36只随机分为3组:对照组、缺血再灌注组和前列地尔组,3组分别在再灌注60min和90min时,检测血清谷丙转氨酶(ALT)、谷草转氨酶 (AST)、乳酸脱氢酶(LDH)水平.取肝中叶检测兔诱导型一氧化氮合酶(iNOS)、髓过氧化物酶(MPO)以及bcl-2、bax和Caspase-3蛋白表达;并用原位缺口末端标记法(TUNEL)染色比较各组肝细胞凋亡.结果 与对照组比较,缺血再灌注组和前列地尔组在再灌注后ALT、AST、LDH 水平均大幅上升(P<0.05);但前列地尔组兔在再灌注60、90min时ALT、AST、LDH 水平明显低于缺血再灌注组(P<0.05);与对照组比较,缺血再灌注组肝细胞bcl-2、bax、Caspase-3的表达明显增强;前列地尔组与缺血再灌注组比较表达均减弱,但仍强于对照组.TUNEL 法显示前列地尔组、缺血再灌注组与对照组比较凋亡细胞数增多,前列地尔组与缺血再灌注组比较凋亡细胞数减少;与对照组比较,缺血再灌注组与前列地尔组iNOS 与MPO的活性明显增强,前列地尔组与缺血再灌注组比较,该两者活性明显减弱.结论 前列地尔在肝脏缺血再灌注损伤时能有效地保护肝功能,减少肝细胞的损伤,其作用机制可能是通过减少细胞脂质过氧化,从而降低bcl-2、bax、Caspase-3等凋亡基因的表达.

Abstract：

Objective To study the protective the positive effects of alprostadil Hepatocyte Apoptosis by Liver Ischemia-Reperfusion Injury in rabbits. Methods Thirty-six rabbits were made the model of liver ischemia-reperfusion injury, and randourly divided into three groups:Control group, Ischemia-Reperfusion Injury group and Alprostadil intervention group. The alanine aminotransferase (ALT) , aspartate aminotransferase (AST) , lactate dehydrogenase (LDH) were determined; Each group inducible nitric oxide synthase (iNOS) , myeloperoxidase (MPO) and bcl-2, bax, Caspase-3 and apoptosis of the hepatocyte by TUNEL were assayed at 60 and 90 min after reperfusion. Results The ALT, AST, LDH concentration in plasma in Ischemia-Reperfusion Injury group and Alprostadil intervention group were increased obviously at 60, 90 min after reperfusion and it was significantly higher than that in the Control group in the same time point (P<0.05). And the ALT, AST, LDH concentration in plasma in Alprostadil intervention group was significantly lower than that in the in Ischemia-Reperfusion Injury group in the same time point (P<0.05). The level of bcl-2, bax, Caspase-3 in the liver tissue in the Control group was smaller, but the obvious increase of the expression those was found in the Ischemia-Reperfusion Injury group and Alprostadil intervention group. Compared with those in the Ischemia-Reperfusion Injury group group, the expression of bcl-2, bax, Caspase-3 in the Alprostadil intervention group werw obviously smaller (P<0.05). The contents of iNOS and MPO in liver tissue in the Ischemia-Reperfusion Injury group and Alprostadil intervention group were significantly higher than that in the Control group (P<0.05). Conclusion Alprostadil could be used to protect liver ischemia-reperfusion injury, it could decrease oxygen free radicals generation, inhibit neutrophils aggregating and activating in the liver, thereby inhibiting expression of bcl-2, bax, Caspase-3.     

Effect of Glutamine and Bile Acid on Hepatocyte Apoptosis after Bile Duct Ligation in the Rat

Apoptosis is an important process in a wide variety of biologic systems. Cholestasis, or impaired bile formation, occurs in a wide variety of human liver diseases. Retention and accumulation of toxic hydrophobic bile salts in hepatocytes may cause hepatocyte toxicity by inducing apoptosis. In addition, the translocation of bacteria and endotoxin, well documented in patients with obstructive jaundice, contribute to the induction of hepatocyte apoptosis. We hypothesized that oral bile acid replacement, glutamine administration, or both can attenuate or abolish hepatocyte apoptosis. Male Sprague-Dawley rats weighing 250 to 300 g were randomized to four groups (10 in each group). Group 1 underwent a sham operation and was simultaneously treated with normal saline. Group 2 underwent common bile duct (CBD) ligation and was simultaneously treated with normal saline. Group 3 underwent CBD ligation and was simultaneously treated with oral glutamine. Group 4 underwent CBD ligation and was simultaneously treated with oral bile acid replacement. After 3 days (n = 5) and 7 days (n = 5), liver tissues were harvested for histopathologic analysis and apoptosis measurements. When compared with the sham operation group, significantly increased hepatocyte apoptosis and ductular proliferation occurred after CBD ligation for either 3 or 7 days. After administration of either glutamine or bile acid, the increased hepatocyte apoptosis and ductular proliferation after CBD ligation for 3 days were significantly diminished. However, both failed to diminish the changes after CBD ligation for 7 days. Significantly increased hepatocyte apoptosis and ductular proliferation occurred after CBD ligation. The administration of either glutamine or bile acid effectively diminished the hepatocyte apoptosis and ductular proliferation after CBD ligation for 3 days, whereas both failed to show the same effect after CBD ligation for 7 days.     

The Effects of Nitric Oxide Supplementation and Inhibition on Bacterial Translocation in Bile Duct Ligated Rats

Obstructive jaundice promotes bacterial translocation from the gut, but the role of nitric oxide is controversial in this process. We studied the effects of nitric oxide synthase substrate, L-arginine, and nitric oxide synthase inhibitor, NG-nitro-¿-arginine methyl ester, on bacterial translocation in bile duct ligated rats. The animals were randomized into five groups; control, sham, common bile duct ligation alone, nitric oxide inhibition, and nitric oxide supplementation. Obstructive jaundice was performed with common bile duct ligation. ¿-arginine or NG-nitro-¿-arginine methyl ester was injected once daily for 14 days. Blood bilirubin level, liver histology, and bacterial translocation to the mesenteric lymph nodes as well as to the liver were assessed. The ¿-arginine supplemented group had the lowest bacterial translocation rate, but the most prominent hepatic fibrosis. Nitric oxide inhibition increased bacterial translocation to the mesenteric lymph nodes. Therefore, the administration of nitric oxide donor or inhibitor acts as a significant regulatory factor for bacterial translocation in obstructive jaundice.