实验性肝硬化大鼠纹状体中神经元及一氧化氮合酶的研究

目的:观察肝硬化大鼠脑纹状体中神经元的变化及一氧化氮合酶(NOS)的表达,探讨纹状体神经元的形态学改变及一氧化氮(NO)在肝硬化和肝性脑病发病机制中的作用。方法:建立CCI4肝硬化模型,用尼氏染色法观察纹状体中神经元的变化,经烟酰胺腺嘌呤二核苷酸-黄递酶(NADPH-d)染色法观察纹状体NOS阳性神经元的变化;用图像分析仪对纹状体神经元进行光密度及数目测定,同时对纹状体NOS的表达程度和数目进行定量分析,并与对照组相比较。结果:肝硬化模型制备成功。肝硬化时纹状体神经元光密度值变小(实验组0.67±0.04,对照组0.78±0.06),数目减少(实验组12.0±3.1,对照组19.7±5.4),纹状体NOS表达增强(阳性神经元平均灰度:实验组148.0±12.1,对照组172.0±10.7;阳性细胞数:实验组14.80±2.59,对照组8.96±1.71)。结论:肝硬化大鼠纹状体中神经元数目减少,尼氏体减少、消失可能是肝硬化并发肝性脑病,尤其是以运动异常为主要表现的肝性脑病的重要组织学基础之一;NO可能介导了神经元的损伤,并参与了肝硬化和肝性脑病的发病。     

肝硬化大鼠下丘脑神经元的形态观察

本文通过对肝硬化大鼠下丘脑神经元形态及数目的定量研究 ,探讨出现复杂症状的组织学基础。材料与方法一、建立肝硬化模型ＳＤ大鼠 40只 ,购自昆明医学院重点实验室 ,雌性 ,体重15 0～ 2 0 0ｇ。随机分成 2组 :实验组 (ｎ =2 0 )予 2 0 %四氯化碳∶橄榄油混合溶液腹部皮下注射     

抗帕颗粒对帕金森病模型大鼠黑质纹状体TH阳性神经元的影响

目的：观察抗帕颗粒对帕金森病模型大鼠黑质纹状体TH阳性神经元的影响。方法：帕金森病(PD)大鼠80只，随机分为4组：对照组、美多巴组、抗帕颗粒组、抗帕颗粒联合美多巴组。于喂养4个月后取黑质纹状体组织免疫组化染色。检测TH阳性神经元的分布、密度。结果：美多巴组黑质TH阳性神经细胞及纹状体TH阳性终末较生理盐水组明显减少。而抗帕颗粒组增多20％～30％。联合组增多最显著达40％～50％。结论：抗帕颗粒可改善PD大鼠黑质纹状体TH阳性神经元的病理改变，抗帕颗粒联合美多巴治疗效果明显。     

氯沙坦对实验性肝硬化大鼠胰岛素抵抗的研究

目的　本实验旨在研究血管紧张素Ⅱ受体 (AT1)阻断剂氯沙坦对实验性肝硬化大鼠血脂、胰岛素敏感性的作用 ,探讨氯沙坦治疗肝硬化胰岛素抵抗的可行性。方法　雄性Wister大鼠 3 5只 ,随机分为 3组 ,正常组 9只 ,模型组及氯沙坦组各 13只 ,采用CCl4、高脂饲料等复合因素造模法。造模结束后 ,用放免法测定血清胰岛素 ,检测血糖、血脂 ,肝组织行切片病理学观察。结果　氯沙坦组与模型组相比较 :①血清胰岛素、血糖含量降低 ,胰岛素敏感性增加均有非常显著性意义 (P <0 0 1) ;②血清甘油三脂(TG)、胆固醇 (Ch)和高密度脂蛋白 (HDLC)含量降低有非常显著性意义 (P <0 0 1) ,低密度脂蛋白 (LDLC)含量无显著性降低 (P >0 0 5 ) ;③肝组织纤维化程度有显著性改善 (P <0 0 1)。结论　氯沙坦可增加肝硬化大鼠胰岛素敏感性 ,改善异常的糖代谢和脂代谢     

实验性氟中毒大鼠中缝背核神经元超微结构研究

以喂饲高氟（１００ｍｇ／Ｌ）水的方法制造了雄性大鼠慢性中毒模型，透射电子显微镜下观察了大鼠中缝背核（ＮＲＤ）神经元的超微结构变化。结果表明，氟中毒大鼠ＮＲＤ神经元出现超微结构改变。主要表现为神经元的核浆比值增大，核内异染色质增多且边集，线粒体扩张，嵴断裂或消失，粗面内质网池，高尔基复合体扁平囊亦扩张。神经元胞体，尤其是突起中脂褐素明显增多，并有较多的自噬体出现。个别神经元固缩。神经纤维有髓鞘松散及     

肝硬化大鼠小肠粘膜形态变化的实验研究

肝硬化可造成多个器官的病理损害和功能紊乱 ,出现多种并发症 ,门脉高压性肠粘膜病变 (ＰＨＥ)是最常见的相关病变之一。有关ＰＨＥ的血管病变已有较多的研究 ,本文就肝硬化大鼠小肠粘膜厚度、绒毛高度及绒毛数量等形态学变化进行初步观察。材料和方法一、实验动物雄性大鼠 2 6只 ,体重 180～ 2 0 0克 (西安医科大学实验动物中心提供 )。随机分为二组 ,肝硬化模型组 13只 ,正常对照组 13只。二、肝硬化大鼠模型的制备肝硬化模型组大鼠由实验第一天起皮下注射 40 %ＣＣｌ4花生油注射液 ,剂量 0 .5ｍｌ/ 10 0 ｇ。以后每隔 3ｄ皮下注射0 .3ｍ…     

大鼠发育中海马CA3区神经元形态、核及核仁的定量分析

目的：观察发育过程中大鼠海马神经元形态特点及其与脑老化的关系。方法：HE染色光镜观察，彩色显微镜图像分析仪分析。结果：随着年龄的增长锥体细胞层的厚度变薄，细胞密度及核仁数量，减少，幼年鼠面积最大，成年鼠核仁／核比值最大。结论：随着年龄的增大，大鼠海马CA3区锥区细胞的数量及形态均发生变化，以及适应功能的需要，这些形态也与脑老化过程有一定关系。     

永久性大脑中动脉闭塞大鼠纹状体P-SAPK/JNK表达与神经元凋亡的相关性

目的 探讨永久性大脑中动脉闭塞(permanent middle cerebral artery occlusion,pMCAO)大鼠纹状体P-SAPK/JNK表达与神经元凋亡的相关性.方法 54只Sprague-Dawley雄性大鼠随机分为假手术组以及pMCAO 1 h、3h、6h、12 h和24 h组,每组9只.应...     

东亚钳蝎毒抑制大鼠实验性大肠癌细胞核中Ag-NOR的定量研究

东亚钳蝎毒是东亚钳蝎毒腺细胞分泌的一种含多种生物活性成份的小分子肽，对大肠癌细胞有显抑杀作用。为了进一步探讨蝎毒素对大肠癌细胞抑杀的作用机制，我们对蝎毒素对Wistar鼠实验性大肠癌细胞核Ag-NOR的影响进行了研究。     

永久性大脑中动脉闭塞大鼠纹状体P—SAPK/JNK表达与神经元凋亡的相关性

目的探讨永久性大脑中动脉闭塞（permanent middle cerebral artery occlusion,pMCAO）大鼠纹状体P-SAPK／JNK表达与神经元凋亡的相关性。方法54只Sprague—Dawley雄性大鼠随机分为假手术组以及pMCAO1h、3h、6h、12h和24h组,每组9只。应用TUNEL法检测纹状体凋亡神经元,免疫组织化学染色法检测纹状体P—SAPK／JNK核转位,Western印迹法检测P-SAPK／JNK蛋白表达。结果pMCAO 1h纹状体TUNEL和P—SAPK／JNK阳性细胞数量显著增多（P=0．0001）,6h达高峰,12h时TUNEL阳性细胞减少,但仍高于假手术组（P=0．0002）。Western印迹分析显示,pMCAO后纹状体P—SAPK／JNK蛋白表达水平显著增高,且时程变化与免疫组化染色结果一致。纹状体神经元凋亡与P—SAPK／JNK蛋白表达呈显著正相关（r=0．984,P=0．0004）。结论脑缺血可能通过激活P-SAPK／JNK诱导纹状体神经元凋亡。     

肝硬化大鼠模型肠壁结构及细菌移位的研究

目的 研究肝硬化大鼠模型肠黏膜结构的改变及细菌移位.方法 采用皮下注射40%四氯化碳诱导大鼠肝硬化模型,比较肝硬化大鼠模型与正常对照组小肠组织结构及超微结构的变化;将肝、脾和肠系膜淋巴结组织匀浆进行细菌培养,了解肠道细菌移位情况;采用鲎实验检测血浆内毒素水平.结果 与正常对照组相比,肝硬化模型组小肠绒毛表面积显著下降(P<0.01),而肠隐窝深度无明显变化(P>0.05),肠黏膜上皮细胞微绒毛明显缩短、稀疏,上皮细胞间紧密连接结构模糊,细胞间隙增大;肝硬化模型组肝、脾、肠系膜淋巴结细菌移位发生率分别为16.67%、16.67%和41.67%,正常对照组未发现细菌生长;肝硬化模型组血浆内毒素水平明显高于正常对照组(P<0.01).结论 肝硬化大鼠模型肠黏膜上皮组织及超微结构发生改变,从而导致肠道细菌移位和血浆内毒素水平的升高.     

肾上腺髓质素在肝硬化大鼠肝脏、门静脉的表达及意义

目的　探测肾上腺髓质素(ADM)在肝硬化大鼠门静脉血浆浓度及在肝脏、门静脉的表达。方法　以CCL4诱导肝硬化大鼠模型,正常大鼠作对照。造模完成后于门静脉采血,同时取门静脉及肝组织。以放射免疫法测定大鼠门静脉血浆ADM浓度。免疫组化染色(SABC法)检测ADM在大鼠肝脏及门静脉的表达,并以Ridit分析作半定量分析。结果　肝硬化大鼠门静脉血浆ADM浓度明显高于正常大鼠(5 3 .61±18.2 7对3 6.84±12 .67,t=3 .2 1,P <0 .0 1)。正常大鼠除肝窦外,肝细胞内也有ADM表达,肝硬化时肝脏和门静脉表达均明显增加(U肝脏=2 .69,P <0 .0 5 ;U门静脉=2 .2 7,P <0 .0 5 )。结论　肝硬化时ADM在肝细胞、肝窦内皮细胞,门静脉血管的表达及门静脉血浆浓度均较正常大鼠升高。肝细胞、肝窦内皮细胞,门静脉表达ADM增加可能是循环ADM浓度增高的一个因素。肝硬化时ADM可能在门静脉压力的调节中发挥重要作用。     

中华麦饭石防治大鼠肝炎,肝硬化和肝癌时微量元素作用

目的：本文旨在探讨中华麦饭石防治大鼠肝炎、肝硬化和肝癌时微量元素的作用方法：给ｗｉｓｔａｒ大鼠食用二甲基奶油黄饲料，同时饮用１０％中华麦饭石浸液共２６周。用ＩＣＰ法检测肝炎、肝硬化和肝癌大鼠全血１０种微量元素。结果：肝炎时实验组仅Ｍｎ显著高于对照组（Ｐ＜００５）。肝硬化时实验组Ｍｎ、Ｓｉ、Ｂａ、Ｆｅ、Ｚｎ和Ｓｅ均显著高于对照组，Ｃｕ显著低于对照组（Ｐ＜００５～０．００１）。肝癌时实验组Ｍｎ、Ｓｉ、Ｂａ、Ｆｅ、Ｚｎ、Ｓｅ和Ｍｏ继续高于对照组，Ｃｕ和Ｃｒ低于对照组（Ｐ＜０００１）。除Ｓｉ外，实验组和正常对照组微量元素差异无显著意义（Ｐ＜００５）。结论：１肝病越重，微量元素变化越明显。２中华麦饭石能维持机体微量元素的正常状态，对大鼠肝炎、肝硬化和肝癌防治具有重要作用。     

柴胡、丹参和五味子配伍对CCl4所致肝硬化大鼠的作用及其机制

目的探讨柴胡＋丹参＋五味子（CHAIDANWU）对肝硬化大鼠的作用及其机制。方法复制大鼠CCl4肝硬化模型，给予CHAIDANWU醇提物治疗，同时体外以醇提物和含药血清作用正常与模型大鼠肝细胞。测定血清酶水平、血清与匀浆HYP、PCI、PCIII含量，TNF—α、CD14、iNOS、MMP-1、TIMP-1在肝组织内阳性表达率，TUNEL法检测肝组织细胞凋亡，DNA琼脂糖凝胶电泳检测体外培养肝细胞凋亡，采用标准积分埘肝细胞的变性及胶原纤维增生程度进行评价。结果CHAIDANWU能明显地降低血清酶活性，体外试验与体内结果一致。血清和肝组织中PCI、PCIII含量，肝组织TNF—α、CD14、iNOS、MMP—1、TIMP—1阳性率及肝细胞凋亡率明显降低，阻滞肝细胞的变性及皎原纤维增生。结论CHAIDANWU阻滞CCl4诱导大鼠肝硬化的作用，这种作用可能与抑制肝非实质激活，细胞因子释放减少，贮脂细胞释放TIMP—1壁降低，胶原纤维分解加速，肝细胞凋亡数减少有关。     

Amelioration of carbon tetrachloride-induced cirrhosis and portal hypertension in rat using adenoviral gene transfer of Akt

AIM:To investigate whether a virus constitutively expressing active Akt is useful to prevent cirrhosis induced by carbon tetrachloride(CCl4).METHODS:Using cre-loxp technique,we created an Ad-myr-HA-Akt virus,in which Akt is labeled by a HA tag and its expression is driven by myr promoter.Further,through measuring enzyme levels and histological structure,we determined the efficacy of this Ad-myrHA-Akt virus in inhibiting the development of cirrhosis induced by CCl4in rats.Lastly,using western blotting,we examined the expression levels and/or phosphorylation status of Akt,apoptotic mediators,endothelial nitric oxide synthase(eNOS),and markers for hepatic stellate cells activation to understand the underlying mechanisms of protective role of this virus.RESULTS:The Ad-myr-HA-Akt virus was confirmed using polymerase chain reaction amplification of inserted Akt gene and sequencing for full length of inserted fragment,which was consistent with the sequence reported in the GenBank.The concentrations of Admyr-HA-Akt and adenoviral enhanced green fluorescent protein(Ad-EGFP)virus used in the current study were5.5×1011vp/mL.The portal vein diameter,peak velocity of blood flow,portal blood flow and congestion index were significantly increased in untreated,saline and Ad-EGFP cirrhosis groups when compared to normal control after the virus was introduced to animal through tail veil injection.In contrast,these parameters in the Akt cirrhosis group were comparable to normal control group.Compared to the normal control,the liver function(Alanine aminotransferase,Aspartate aminotransferase and Albumin)was significantly impaired in the untreated,saline and Ad-EGFP cirrhosis groups.The Akt cirrhosis group showed significant improvement of liver function when compared to the untreated,saline and Ad-EGFP cirrhosis groups.The Hyp level and portal vein pressure in Akt cirrhosis groups were also significantly lower than other cirrhosis groups.The results of HE and Van Gieson staining indicated that Akt group has better preservation of     

肝炎肝硬化患者肾功能分析39例

目的:探讨肝炎肝硬化患者的肾功能损害方法:检测39例不同分期肝硬化患者(肝硬化组,肝功能Child A,B,C级分别为15例,12例,12例)和20例体检正常者(对照组)的肌酐清除率(Ccr)、尿微量白蛋白(UmALB)、尿α1-MG(Uα1-MG)、尿β2-MG(Uβ2-MG)、尿NAG酶(NAG-U)、尿转铁蛋白(TRF-U)和尿视黄醇结合蛋白(RBP)的活性.结果:Child C组的Ccr低于对照组和Child A,B组(51.54±25.79 vs 105.41±13.75,95.61±23.09,89.16±18.19,P<0.05),而后3组间没有差别.Child B、C组UmALB高于对照组和Child A组(42.53±19.12,108.07±41.64 vs 14.10±3.26,13.11±2.72,P<0.05);ChildA,B组的Uα1-MG、Uβ2-MG、NAG-U、RBP与对照组无差别,而Child C组对应指标高于对照组和Child A,B组(26.95±35.34 vs 6.81±1.88,6.87±2.10.5.66±0.81;747.78±596.72 vs 108.85±65.86,115.00±73.83,147.25±91.55;32.30±16.91 vs 15.68±3.14,17.13±5.35,18.90±10.23;281.98±133.19 vs 119.63±25.94,124.39±34.90,168.25±11.76;P<0.05).肝硬化Child A.B.C组的TRF-U与对照组比较均有显著性差异(6.54±2.28,7.59±3.21,8.04±5.64 vs 0.47±0.21,P<0.05),肝硬化3组间无差别.结论:UmALB、Uα1-MG、Uβ2-MG和NAG活性的测定有助于早期发现肝炎肝硬化患者的肾功能损害,TRF-U和RBP不适合作为肝硬化患者早期肾功能损害的研究指标.     

超声定量诊断大鼠肝纤维化的研究

目的 探讨超声定量诊断大鼠肝纤维化的价值.方法 收集正常或肝纤维化大鼠共90只的标准化声像图,观测肝包膜厚度并提取声像图纹理的13个灰度共生矩阵参数(熵、对比、方差、均值和、方差和、和熵、方差差、差熵及相关信息2递增、相关信息1、角二阶矩、相关及逆差矩)与肝纤维化病理学诊断结果比较,进行逐步判别分析建立判别大鼠肝纤维化程度的超声定量模型,用交互检验评价模型的效率.结果 肝包膜厚度及其他13个指标与肝纤维化病理学分期均具有相关性(r值依次为0.817、0.894、0.808、0.844、0.828、0.795、0.864、0.725、0.821、0.848、-0.743、-0.909、-0.438、-0.855,P值均＜0.05),14个指标在病理学分期间的差异均具有统计学意义(F值分别为43.12、60.55、50.70、43.65、45.68、23.63、56.60、21.48、46.19、24.66、39.52、75.74、15.37、63.98,P值均＜0.05).交互检验结果显示建立于超声定量指标基础上的判别模型对大鼠肝纤维化S0、S1、S2、S3和S4分期的准确率分别为83.3％、84.2％、70.0％、50.0％和88.2％,73.3％的大鼠能够被准确分期;对无纤维化组(S0),轻度纤维化组(S1),中重度纤维化组(S2及S3)和早期肝硬化组(S4)分组的准确率分别为91.7%、84.2％、69.0％和88.2％,78.9％的大鼠能够被准确分组.结论 超声检查结合声像图的纹理分析对定量诊断大鼠肝纤维化具有较高的准确性.     

Non-invasive predictors of the presence of large oesophageal varices in patients with cirrhosis

BACKGROUND/AIMS: The usual clinical practice is to screen all patients with established cirrhosis at the time of diagnosis by upper endoscopy for the presence of varices. Patients with large varices should be treated with non-selective beta blockers to reduce the incidence of first variceal bleeding. However, fewer than 50% of cirrhotic patients have varices at screening endoscopy and most have small sized varices, with a low risk of bleeding. The aim of the present study was to determine whether clinical or laboratory non-endoscopic parameters could predict the presence of large oesophageal varices. PATIENTS/METHODS: Seventeen variables considered relevant to the prevalence of oesophageal varices were tested in 184 patients with cirrhosis, who underwent screening endoscopy. Small varices were regarded as those which flatten with insufflation or slightly protrude into the lumen, while large varices are those which protrude into the lumen or touch each other. None of the patients was on beta blockers or other vasoactive drugs or had a history of variceal bleeding. RESULTS: Oesophageal varices were present in 92 patients (50%), and large varices in 33 patients (17.9%).Variables associated with the presence of large oesophageal varices on univariate analysis were the presence of ascites and splenomegaly either by clinical examination or by ultrasound (p < 0.01), the presence of spiders (p = 0.02), platelet count (p < 0.0001), and bilirubin (p = 0.01). Factors independently associated with the presence of large oesophageal varices on multivariate analysis were platelet count, size of spleen and presence of ascites by ultrasound. Using mean values as cut-off points, it is noteworthy that only five out of 39 patients (12.8%) with platelets > or = 18(x 10(9)/l), spleen length < or = 135 mm and no ascites had varices. Moreover, all these patients had small sized varices. On the other hand, 15 out of 18 patients (83.3%) with a platelet count < 118 x 10(9)/l, spleen length > 135 mm and ascites had varices. Moreover, five out of those 18 patients had large varices (28.3%). CONCLUSION: Thrombocytopenia, splenomegaly and ascites are independent predictors of large oesophageal varices in cirrhotic patients. We suggest that endoscopy could be avoided safely in cirrhotic patients with none of these predictive factors, as large varices are absent in this group of patients.     

拉米夫定治疗乙型肝炎肝硬化的临床观察

目的观察拉米夫定治疗乙型肝炎肝硬化的临床疗效。方法选择Child-Pugh A、B级乙型肝炎肝硬化70例,36例接受拉米夫定治疗2~3年,另34例不规则口服护肝药物。结果治疗或随访至3年时,接受拉米夫定治疗的患者HBeAg阴转、HBeAg/抗HBe血清转换和HBV DNA阴转率分别为50%、44.4%和77.3%,显著高于对照组;Child-Pugh计分为7.5±1.1,而对照组为9.1±1.3(P<0.05);两组ALT复常率和发生肝衰竭和肝细胞癌情况无显著性相差。2例HBV相关性肾病患者病情恢复、稳定。结论拉米夫定治疗乙型肝炎肝硬化的临床效果肯定,可以延缓病情进展。     

Clinical outcomes of acute pancreatitis in patients with cirrhosis

BackgroundAP outcomes in cirrhotic patients have not yet been studied. We aim to investigate the outcomes of cirrhotics patients with acute pancreatitis.MethodsThe National Inpatient Sample (NIS) database (2003–2013) was queried for patients with a discharge diagnosis of AP and liver cirrhosis. Cirrhosis was further classified as compensated and decompensated using the validated Baveno IV criteria. Primary outcome was inpatient mortality. The analysis was adjusted for age, gender, race, Charlson comorbidity index (CCI), median income quartile, and hospital characteristics.ResultsOver 2.8 million patients with acute pancreatitis were analyzed. Cirrhosis prevalence was 2.8% (80,093). Both compensated and decompensated cirrhosis subjects had significantly higher mortality. Highest odds ratios (OR) were: inpatient mortality (OR 3.4, P < 0.001), Shock (OR 1.5, P = 0.02), Ileus (OR: 1.3, p = 0.02, ARDS (OR 1.2, p = 0.03), upper endoscopy performed (OR 2.0, p < 0.001), blood transfusions (OR 3.1, p < 0.001), gastrointestinal bleed (OR 5.5, p < 0.001), sepsis (OR 1.3, p = 0.005), portal vein thrombosis (PVT) (OR 7.2, p < 0.001), acute cholecystitis (OR 1.3, p < 0.001). Interestingly, cirrhosis patients had lower hospital length of stay, (OR 0.16, p < 0.001), AKI (OR 0.93, p = 0.06), myocardial infarction (OR 0.31, p < 0.001), SIRS (OR 0.62, p < 0.001), parenteral nutrition requirement (OR 0.84, p = 0.002). Decompensated cirrhosis had higher inflation-adjusted hospital charges (+$3896.60; p < 0.001).ConclusionAP patients with cirrhosis have higher inpatient mortality, but it is unlikely to be due to AP severity as patients had lower incidence of SIRS and AKI. Higher mortality is possibly related to complications of cirrhosis and portal hypertension itself such as GI bleed, shock, PVT, AC and sepsis.