越鞠丸对非酒精性脂肪肝病大鼠肝脏PPARα表达的影响

目的 观察越鞠丸对非酒精性脂肪肝(NAFLD)大鼠肝脏过氧化物酶体增殖物活化受体α(PPARα)表达的影响.方法 采用喂饲高脂饲料的方法复制NAFLD大鼠模型,实验分组为正常对照组、模型组、东宝肝泰对照组和越鞠丸高、低剂量组.提取肝脏总RNA,运用半定量RT-PCR方法观察各组大鼠肝脏PPARα mRNA的表达情况,同时测定各组大鼠血清总胆固醇(TC)、甘油三酯(TG)、游离脂肪酸(FFA)和肝组织匀浆TC、TG的含量,并做病理切片.结果 模型组大鼠PPARα mRNA的含量明显降低,血脂和肝脏脂质含量明显升高,肝脏呈明显脂肪变性,经药物治疗后,各治疗组大鼠肝脏PPARα mRNA表达明显增强,血脂和肝脏脂质含量显著降低,肝脂变程度明显减轻.结论 越鞠丸能增强NAFLD大鼠肝脏PPARα mRNA的表达,可能是其治疗NAFLD的分子机制之一.     

银杏总黄酮对NAFLD大鼠生化指标及血清脂联素水平的影响

[目的]探讨银杏总黄酮对非酒精性脂肪肝(NAFLD)大鼠发病过程中生化指标及血清脂联素(Adipo)水平的影响。[方法]72只SPF级雄性大鼠随机分为3组:正常对照组、NAFLD模型组、银杏总黄酮治疗组。利用高脂饲料喂养法构建NAFLD大鼠模型。观察各组大鼠肝脏组织形态改变。全自动生化分析仪测定血清丙氨酸转氨酶(ALT)、天门冬氨酸氨基转移酶(AST)、三酰甘油(TG)、总胆固醇(TC),酶联免疫吸附法(ELISA)测定血清Adipo含量,RT-PCR和Western-blot法分别测定肝组织AdipoR_2mRNA及蛋白表达。[结果]随着时间延长,NAFLD模型组大鼠血清ALT、AST、TG、TC含量逐渐增高,血清Adipo含量逐渐减少,肝组织中AdipoR_2mRNA及蛋白表达水平逐渐下降;银杏总黄酮治疗组大鼠血清ALT、AST、TG、TC含量逐渐降低,血清Adipo含量、肝组织AdipoR_2mRNA及蛋白表达水平逐渐增加,与NAFLD组比较均差异有统计学意义(P0.05)。[结论]银杏总黄酮对NAFLD大鼠肝脏有防治作用,降低血清ALT、AST、TG、TC含量,可能通过增加AdipoR_2表达所致。     

双歧杆菌对高脂饮食诱导非酒精性脂肪性肝病大鼠血脂代谢的影响

目的探讨双歧杆菌对高脂饮食诱导非酒精性脂肪性肝病大鼠血脂代谢的影响。方法将45只雄性SD大鼠随机等分为对照组、模型组和治疗组。对照组喂以普通饲料,模型组喂以高脂饲料,治疗组喂以高脂饲料和双歧杆菌。6 w后比较各组大鼠肝指数和肝组织学改变,检测血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、总胆固醇(TC)和甘油三酯(TG)的水平以及肝总脂肪(HLs)含量,采用荧光实时定量RT-PCR测定禁食诱导脂肪因子(FIAF)mRNA的表达。结果模型组肝指数和肝组织脂肪变性程度均显著高于对照组(P0.05);而治疗组肝指数和肝组织脂肪变性程度均显著低于模型组(P0.05)。与对照组比较,模型组ALT、AST、TC、TG和HLs水平显著升高(P0.05);与模型组比较,治疗组ALT、AST、TC、TG和HLs水平显著降低(P0.05)。与对照组比较,模型组FIAF mRNA的表达显著升高(P0.05);与模型组比较,治疗组FIAF mRNA的表达显著降低(P0.05)。结论双歧杆菌能够降低NAFLD大鼠的血脂水平,减少肝脏组织中脂肪的沉积,改善肝脏的炎症反应,其机制可能与调节脂质的摄入和抑制FIAF基因的表达有关。     

消脂护肝方对非酒精性脂肪肝大鼠脂质过氧化的影响

目的:探讨中药"消脂护肝方"对非酒精性脂肪肝(NAEL)大鼠脂质过氧化(LP)的影响.方法:用CCl4和高脂饮食复合方法建立大鼠NAFL模型,造模期间给予中药"消脂护肝方"和西药"东宝肝泰"干预,6周后检测肝功能、血脂并观察肝组织病理变化,检测肝组织脂质含量和超氧化物歧化酶(SOD)、谷胱甘肽过氧化酶(GSH-PX)及丙二醛(MDA)的含量.结果:中药组和西药组肝组织病理改变较模型组明显减轻,肝组织脂质含量及MDA含量较模型组明显降低,SOD、GSH-PX含量则明显升高.结论:①消脂护肝方具有保护肝功能、降低血脂、抗肝脏脂质沉积的作用;②消脂护肝方具有减轻大鼠NAFL模型肝组织细胞LP反应的作用,对LP导致肝脏脂肪变性具有抑制作用.     

疏肝消脂方防治高脂饮食诱导的非酒精性脂肪性肝炎大鼠的实验研究

目的:通过对疏肝消脂方防治高脂饮食诱导的非酒精性脂肪性肝炎(NASH)大鼠模型的实验研究,探讨其治疗NASH的作用机理。方法:取Wistar雄性大鼠90只,随机数字表法分成正常组、高脂模型组和非诺贝特组和疏肝消脂方低、中、高剂量组。除正常组予普通饲料外,其余各组大鼠均给予高脂饲料复制非酒精性脂肪性肝炎大鼠模型。12周后,HE染色观察大鼠肝组织的病理变化,测定大鼠肝组织甘油三酯(TG)、胆固醇(TC)含量变化,应用RT-PCR法检测大鼠肝组织中过氧化物酶体增殖物激活受体(PPARα)和固醇调节元件结合蛋白-1c(SREBP-1c)基因表达情况。结果:与正常组比较,模型组大鼠脂质指标TG、TC含量明显增加,出现肝脏脂肪变性及炎症。与模型组相比,疏肝消脂方低、中、高剂量均能降低大鼠肝组织TG、TC的含量,提高PPARα表达,显著降低SREBP-1c表达。结论:疏肝消脂方能减轻肝脏脂肪沉积,上调PPARα、下调SREBP-1c的表达可能是其治疗NASH的作用机制之一。     

疏肝消脂Ⅲ方胶囊对非酒精性脂肪性肝病大鼠肝组织过氧化物酶体增殖物激活受体γ及脂联素受体2表达的影响

目的:探讨疏肝消脂Ⅲ方胶囊对非酒精性脂肪肝性肝病(NAFLD)大鼠的防治作用及对肝组织过氧化物酶体增殖物激活受体γ(PPAR-γ)和脂联素受体2(Adipo R2)mRNA表达的影响。方法:将46只大鼠分为4组,除正常组(10只)外,其余3组大鼠(各12只)均用高脂乳剂灌胃建立NAFLD模型,于灌胃第6周末形成脂肪肝后,分别给消脂方和水飞蓟组大鼠灌胃疏肝消脂Ⅲ方胶囊和水飞蓟宾胶囊4周,检测大鼠血糖(FBG);应用酶联免疫法(Elisa)法检测胰岛素(FINS)含量并计算胰岛素抵抗指数(HOMA-IR);荧光定量(qPCR)法测定大鼠肝组织PPAR-γ、Adipo R2的mRNA表达。结果:①两药物组大鼠FBG、FINS和H0MA-IR水平较模型组降低(P0.05);②消脂Ⅲ方组大鼠PPAR-γ、Adipo R2的mRNA水平较模型组升高(P0.05)。结论:疏肝消脂Ⅲ方胶囊能改善NAFLD大鼠胰岛素抵抗,保护肝脏,作用机制可能与PPAR-γ、Adipo R2表达有关。     

超微脂康饮对非酒精性脂肪性肝病大鼠模型的疗效

目的观察超微脂康饮对实验性非酒精性脂肪肝(NAFLD)大鼠模型的疗效。方法 SD大鼠高脂饮食饲养6周后诱导非酒精性脂肪肝大鼠模型,肝脏病理切片证实造模成功;造模大鼠50只随机分为5组,超微脂康饮(低、中、高剂量)组给予相应剂量的超微脂康饮灌胃,壳脂胶囊组给予壳脂胶囊混悬液,模型组及空白组灌服蒸馏水,除空白组外,其余组仍予高脂饮食。6周后分别检测各组的肝功能、血脂、肝脂及肝脏组织学改变。各组之间比较采用单因素方差分析。结果超微脂康饮各组血清ALT、AST、肝组织脂质(TC、TG)等方面均优于模型组,差异均有统计学意义(P值均0.05),超微脂康饮中,低剂量组血清TG、TC显著优于模型组,差异均有统计学意义(P值均0.05);超微脂康饮各组血清ALT、AST、肝组织TC与壳脂胶囊组比差差异无统计学意义(P值均0.05)。模型组及超微脂康饮各组均存在不同程度的肝脏炎症活动度,但与模型组比较,超微脂康饮各组、壳脂胶囊组大鼠的肝脏炎症活动度均有不同程度的改善(P值均0.05),而壳脂胶囊组较超微脂康饮各组改善稍明显(P值均0.05)。结论超微脂康饮能改善NAFLD大鼠肝功能、降低血脂、抑制肝脏炎症,整体疗效与壳脂胶囊相当,对非酒精性脂肪肝具有一定疗效。     

三七理血脂肝方对大鼠非酒精性单纯性脂肪肝的药效学研究

目的：探讨三七理血脂肝方对大鼠非酒精性单纯性脂肪肝（ non-alcoholic fatty liver , NAFL）的治疗作用,进而探讨其作用机制。方法：雄性 Wistar 大鼠36只,随机分成正常组（ C）、模型组（ M）、三七理血脂肝方组（ Y）,每组12只。 C组给予普通饲料, M和Y组予高脂饲料造模,4周后继续予高脂饲料同时Y组大鼠予相应药物干预4周。动物实验结束时,取3组大鼠肝脏组织用苏木精-伊红染色、油红O染色进行病理学观察,检测肝组织甘油三酯（TG）、总胆固醇（TC）含量。检测血清丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）的活性,以及血脂血糖指标TG、 TC、低密度脂蛋白胆固醇（ LDL-C）、高密度脂蛋白胆固醇（ HDL-C）、游离脂肪酸（ FFA）、空腹血糖（FBG）。蛋白免疫印迹法检测肝组织细胞色素P450亚型2E1（cytochrome P4502E1, CYP2E1）和解耦联蛋白2（uncoupling protein-2, UCP2）的表达水平。结果： M组大鼠血清ALT和LDL-C 较C组显著升高, Y组中这两个指标较M组明显下调,并能降低血清FFA水平; M组大鼠肝组织出现弥漫性大泡性脂肪变性,肝组织 TG、 TC含量显著升高, Y组大鼠肝脏的脂肪变性从分布和程度上均有所减轻,肝脂含量降低。另外M组大鼠肝脏的CYP2E1的表达上调、 UCP2下调, Y组表达趋向正常水平。结论：三七理血脂肝方对大鼠NAFL治疗有效,方药的降脂理血功效可能通过抑制氧化应激、调节脂质代谢发挥降脂保肝作用。     

疏肝健脾方药对非酒精性脂肪性肝炎大鼠肝组织核因子-κB mRNA及蛋白表达的影响

目的探讨疏肝健脾方药对非酒精性脂肪性肝炎(NASH)大鼠肝组织核因子(NF)-κB mRNA及蛋白表达的影响。方法采用高脂饲料喂养复制NASH大鼠实验模型,施以造模因素的同时,各用药组大鼠分别灌服疏肝方、健脾方和疏肝健脾合方的高、低剂量进行干预。16 w后,各组大鼠以3%戊巴比妥钠腹腔麻醉,腹主动脉采血,全自动生化分析仪检测血清总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)含量,肝组织TC、TG含量;HE染色和油红O染色观察肝组织病理变化;实时定量PCR法检测肝组织NF-κB mRNA表达水平;Western印迹法检测肝组织NF-κB蛋白表达水平。结果与正常组相比,模型组大鼠肝细胞脂肪变性明显,血脂及肝脂均有不同程度的升高(P<0.05,P<0.01),大鼠肝组织NF-κB mRNA及蛋白表达明显升高(P<0.01);与模型组相比,各用药组血脂和肝组织NF-κB mRNA及蛋白的表达均较模型组显著降低(P<0.05,P<0.01),尤以综合方高剂量及健脾高剂量作用最为显著。结论疏肝健脾方药对高脂饮食诱导的大鼠NASH有较好的防治作用,其机制可能与其下调肝脏NF-κB mRNA及蛋白的表达有关。     

动态观察非酒精性脂肪肝大鼠肝脏抵抗素的表达

目的观察非酒精性脂肪性肝病(NAFLD)模型大鼠肝脏抵抗素mRNA的动态表达,探讨抵抗素在大鼠NAFLD发病中的作用。方法雄性Wistar大鼠48只随机分为正常对照组(C组)和模型组(M组),C组给予普通饲料,M组给予高脂饮食喂养,分别于9,13,17周末处死各组大鼠。测定大鼠血清肿瘤坏死因子α(TNF-α)、游离脂肪酸(FFA)、甘油三酯(TG)、总胆固醇(TC),以及肝组织TG,测定空腹血糖(FBS)、空腹胰岛素(FINS),并计算胰岛素敏感指数(ISI)。应用半定量RT-PCR检测各组大鼠肝脏组织抵抗素mRNA的表达;HE染色观察肝脏组织病理变化并计算炎症活动度计分。结果第9,13,17周末M组大鼠抵抗素mRNA相对表达量显著高于C组(P<0.01),且随造模时间延长表达量显著增加(P<0.01)。M组大鼠血清FFA、TG、TC、TNF-α及肝组织TG较同期C组均显著升高(P<0.01),ISI显著降低(P<0.01)。相关分析显示,M组大鼠各时点肝脏抵抗素mRNA相对表达量与血清TNF-α水平均呈正相关(r=0.787,0.888,0.873,P<0.05,P<0.01,P<0.01);在第9,13周末与肝脏炎症活动度计分呈正相关(r=0.861,0.892,P<0.01);而与ISI在第9周末呈负相关(r=-0.843,P<0.01)。结论高脂饮食NAFLD模型大鼠肝脏抵抗素基因表达随造模时间的延长而增加,抵抗素可以通过胰岛素抵抗及对炎症因子的调控参与NAFLD的发生发展。     

Multiple necrotic nodules of the liver simulating liver metastasis

A 70‐year‐old man was referred to our hospital due to anemia and elevated serum tumor marker levels. He had advanced colon cancer, and hepatic lesions were found incidentally. On ultrasonography (US) and computed tomography (CT), the hepatic lesions had a maximum diameter of 20 mm and were located in Couinaud's segments V, VI, VII, and VIII, which suggested liver metastasis. On early‐ and late‐phase CT during hepatic arteriography (CTHA), all of the lesions had rim enhancement. On early‐phase CT during arterioportography (CTAP), all of the lesions were seen as nodules with an irregular perfusion defect, and on late‐phase CTAP, all the lesions gradually became iso‐dense, and their shape and size changed. Based on the CTAP findings, these lesions were thought to be fibrotic tumors. Partial resection of the liver (including the lesions in Couinaud's segments V and VIII) was done. Histological examination revealed that the lesions were necrotic nodules. Thus, CT angiography (CTHA and CTAP) was useful for identifying necrotic nodules, because their appearance on this modality is different from that of liver metastases.     

Segmentectomy of the liver

Segmentectomy is anatomical resection of segments based on the classification of Couinaud. This procedure is performed mainly for hepatocellular carcinoma. Invasion of portal vein and intrahepatic metastases often occur with hepatocellular carcinoma. Thus, it is desirable to perform anatomical resection of the cancer-bearing areas for curative purpose. However, segmentectomy is selected when extensive resection must be avoided to preserve liver function. There are major differences between segmentectomy of the left hemiliver (Sg 2-4) and right hemiliver (Sg 5-8). In the former, the branches (third-order branches) arising from the umbilical portion of the portal vein can be ligated prior to liver resection. In the latter, manipulation is difficult. Therefore, ultrasonically guided segmental staining is performed by puncturing the portal branch and injecting a dye. This report described techniques for segmentectomy.     

Carcinosarcoma of the liver

Herein we present a 73-year-old man with primary carcinosarcoma of the liver, a rare malignant tumor of the liver. The case was followed up due to HBV-related liver cirrhosis. Regular check-up by ultrasound demonstrated a hyperechoic tumor in the left lobe of the liver, and he was referred and admitted to our hospital. Dynamic CT studies revealed a mostly hypoenhancing hepatic mass with a peripheral ring enhancement. Surgical resection was performed, and the resected tumor was macroscopically a simple nodular type, 3 cm in diameter, with a dense fibrous capsule. Microscopically, undifferentiated cells were dominant in the tumor, while moderately differentiated hepatocellular carcinoma (HCC) were also observed. A transitional zone was noted between the undifferentiated tumor and HCC. Tumor tissue with adenocarcinoma, osteosarcoma and chondrosarcoma were also detected. Immunohistochemical studies demonstrated that tumor cells were HepPar 1 positive in hepatocellular carcinoma, and CK19 and partly CK7 positive in adenocarcinoma. Moreover, CD56, chromogranin A and c-kit were occasionally positive in undifferentiated tumor cells. The diagnosis of carcinosarcoma was made based on the concomitant presence of HCC and sarcomatous components, yet it is noteworthy that various types of tumor cells were observed.     

Xenotransplantation of the liver

Xenotransplantation of the liver, in its broadest conception, might involve the transplantation of an intact organ or xenogeneic hepatocytes, or the use of an intact xenogeneic liver or cells as an ex vivo "device." The indications for xenotransplantation include not only hepatic failure but also, potentially, the treatment of metabolic diseases. The hurdles to xenotransplantation include immune, physiologic, and infectious complications. New information and progress in experimental systems are bringing xenotransplantation closer to clinical application.