五味子通过促进内源性干细胞增殖对肝硬化治疗的作用  

Wuweizi protects against liver cirrhosis by promoting endogenous stem cell proliferation

作　　者：阮梦婷 金世柱[1] 刘自帅 张菲菲[1] 张春伟[1] 韩明子[1] 

机构地区：[1]哈尔滨医科大学附属第二医院消化科,黑龙江省哈尔滨市150086

出　　处：《世界华人消化杂志》2016年第22期3373-3380,共8页World Chinese Journal of Digestology

摘　　要：目的:本文在于探讨五味子通过促进内源性干细胞增殖治疗肝硬化的机制.方法:通过CCl_4复制大鼠肝硬化模型成功后,将大鼠随机分成实验组(小剂量组A1、中剂量组A2和大剂量组A3)、空白组C及模型组M,小剂量组给予五味子1.0 mg/200 g,中剂量组给予1.5 mg/200 g,大剂量给予2.0 mg/200 g.观察五味子对肝硬化大鼠肝脏组织病理学、肝功[谷草转氨酶(aspartate transaminase,AST)、谷丙转氨酶(alanine transaminase,ALT)和白蛋白(albnmin,ALB)]、肝纤维化的影响以及通过免疫荧光法和免疫组织化学法观察五味子对Brdu标记的内源性干细胞的增殖情况及CK-18、ALB及甲胎蛋白(α-fetoprotein,AFP)三种蛋白的表达情况.结果:通过病理切片HE染色及Masson染色,治疗组的肝硬化大鼠肝细胞变性坏死及肝纤维化程度有一定的改善,各治疗组的肝纤维化评分各异(P<0.05),与模型组相比,中剂量组的肝纤维化评分改善最明显(P<0.01),在免疫组织化学中,发现各治疗组ALB、C K-18及A F P的蛋白表达不同(P<0.05),用B r d u标记肝脏处于分裂间期的干细胞,通过"区域共存"观察到各治疗组干细胞的增殖和分裂,并用免疫荧光法半定量统计发现,各治疗组中ALB、CK-18及AFP的蛋白表达不同(P<0.01),中剂量组表达最显著(P<0.01),在从眼球采血评估肝硬化大鼠肝功能中,各治疗组的肝功能均有一定程度的改善(P<0.05),与对照组相比,中剂量组的AST、ALT明显下降,ALB明显改善(P<0.01).结论:五味子对损伤的肝脏细胞有保护作用,并能延缓肝硬化的进展,机制有可能与五味子通过促进内源性干细胞增殖防治肝硬化有关.AIM：To investigate the mechanism for Wuweizi to treat liver cirrhosis.METHODS：A rat model of liver cirrhosis was developed with CCl_4.Rats were randomly divided into five groups：three treatment groups[small dose Wuweizi group（A1）,middle dose group（A2） and high dose group（A3）],a blank group（C） and a model group（M）.Except group C,liver cirrhosis was induced in all other groups.Groups Al,A2 and A3 were given 1.0,1.5 and 2.0 mg/200 g Wuweizi,respectively.After treatment,histopathology,liver function[aspartate transaminase（AST）,alanine transaminase（ALT） and albumin（ALB）],hepatic fibrosis,stem cell proliferation,and the expression ofCK-18,ALB andα-fetoprotein（AFP） were assessed.RESULTS：In the treatment groups,there was an improvement in the degree of hepatic fibrosis and the condition of liver cell degeneration and necrosis,as revealed by HE staining and Masson staining,and the liver fibrosis scores were different among each treatment group（P〈0.05）.Compared with group M,the liver fibrosis score of group A2 was improved most obviously（P〈0.01）.Immunohistochemistry analysis showed that the expression of CK-18,ALB and AFP was different between each treatment group（P〈0.05）.By labeling liver tissue stem cells with BrdU,the proliferation and division of stem cells were observed through the method of ＂regional coexistence＂.Immunofluorescence analysis revealed that the expression of CK-18,ALB and AFP were different among each treatment group（P〈0.01）,with group A2 having the most prominent expression（P〈0.01）.Liver function was improved differently in each treatment group（P〈0.05）.Compared with group M,AST and ALT were decreased most significantly and ALB increased most obviously in group A2（P〈0.01）.CONCLUSION：Wuweizi has a protective effect on injured liver cells.Wuweizi could delay the process of liver cirrhosis via mechanisms possibly related to promoting the proliferation of endogenous stem cells.

关 键 词：五味子 肝硬化 内源性干细胞 增殖 肝功能 

分 类 号：R285.5[医药卫生—中药学]