熊去氧胆酸减弱日本血吸虫诱导的肝纤维化  

Ursodeoxycholic acid alleviates Schistosoma japonicum induced liver fibrosis in mice

作　　者：王学国 黎东明 赵红岩 林师佈 黄小龙[2] 杨青壮 李旺 杨彦[2] Xue-Guo Wang Dong-Ming Li Hong-Yan Zhao Shi- Bu Lin Xiao-Long Huang Qing-Zhuang Yang Wang Li Yan Yang(Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Hainan Medical University, Haikou 570311, Hainan Province, China Department of Hepatobiliary Surgery, the First Affiliated Hospital of Hainan Medical University, Haikou 570102, Hainan Province, China)

机构地区：[1]海南医学院第二附属医院肝胆外科,海南省海口市570311 [2]海南医学院第一附属医院肝胆胰外科,海南省海口市570102

出　　处：《世界华人消化杂志》2017年第28期2544-2550,共7页World Chinese Journal of Digestology

基　　金：海南省自然科学基金资助项目;No.20168299~~

摘　　要：目的研究熊去氧胆酸(ursodeoxycholic acid,UDCA)对血吸虫肝纤维化的治疗作用.方法正常6-8周龄♀C57BL/6J小鼠67只,随机分为正常组、感染组、感染组+UDCA1、感染组+UDCA2、感染组+UDCA3,每组13-14只.小鼠经腹部感染构建肝纤维化模型.各组给予相应浓度UDCA溶液,灌胃8 wk后,检测血清损伤指标天冬氨酸转氨酶(aspartate transaminase,AST)、丙氨酸转氨酶(alanine transaminase,ALT)、纤维化指标透明质酸(hyaluronic acid,HA)、层黏蛋白(laminin,LN),胶原纤维染色(Masson三色染色)观察各组胶原纤维面积比变化;免疫组织化学法检测Col1及α-平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)在小鼠肝组织中的表达.结果8 wk后,UDCA处理后,血清AST、ALT、HA和LN有明显降低(P<0.05);肝组织纤维间隔变细或消失,形成弥漫性肝硬化结节减少,胶原面积比降低(P<0.05);免疫组织化学结果显示,用药后Col1及α-SMA阳性表达减少,图像软件半定量分析结果显示差异有显著性(P<0.05),且这种结果有浓度依赖性.结论UDCA对血吸虫肝纤维化有明显的改善作用,主要是通过保护肝脏、减轻肝损伤,降低细胞外基质合成等途径减弱肝纤维化的进程.AIM To evaluate the therapeutic effect of ursodeoxycholic acid（UDCA） on liver fibrosis induced by Schistosoma japonicum.METHODS Sixty-seven 6-8-week-old female C57 BL/6J mice were randomly divided into a control group, an infection group, and three UDCA treatment groups（n = 13 or 14 each）. Liver fibrosis was induced in mice of all groups except the control group by abdominal infection with Schistosoma japonicum. UDCA at 50,90 and 140 mg/（ kg·d） was intragstrically given to the three UDCA treatment groups.Eight weeks after treatment, serum aspartate transaminase（AST）, alanine transaminase（ALT）, hyaluronic acid（HA）, and laminin（LN） were measured; collagen fiber was stained by Masson＇s trichromatic staining to detect the change in collagen fiber area;and the expression of type Ι collagen（COL1）and α-smooth muscle actin（α-SMA） in liver tissues was detected by immunohistochemical method.RESULTS After UDCA t reatment, serum level sof AST, ALT, HA, and LN were significant lyreduced; liver fibrous septa became thinner or disappeared; and the number of diffuse cirrhosis nodules and the area of collagen became significantly lower（ P〈 0. 05）.Immunohistochemical staining showed that COL1 and α-SMA expression was significantly decreased（P〈 0.05）, in a concent ration dependent manner.CONCLUSION UDCA alleviates schistosomiasis liver fibrosis,mainly by protecting the liver and reducing liver damage and extracellular matrix synthesis.

关 键 词：熊去氧胆酸 血吸虫肝纤维化 治疗作用 

分 类 号：R575.2[医药卫生—消化系统]