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

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.