四氯化碳诱导性肝纤维化大鼠肝组织骨形态发生蛋白-7的表达

目的 探讨四氯化碳(CCl4)诱导性肝纤维化大鼠的肝组织纤维化与骨形态发生蛋白-7(BMP-7)表达的相互关系.方法 将健康雄性 Wistar 大鼠随机分为对照组和肝纤维化组.对照组大鼠每周一、四背部皮下注射橄榄油(0.12ml/100g),肝纤维化组每周一、四背部皮下注射60% CCl4橄榄油(0.3ml/100g),连续注射6、10、16 和21周.实验结束时处死大鼠,取肝中叶,石蜡包埋、切片.行天狼猩红染色,观察肝组织胶原纤维的增生情况;行BMP-7免疫组织化学染色和 Western blotting 检测,观察肝组织.BMP-7的表达.结果 天狼猩红染色显示对照组大鼠仅在肝门静脉及门管区看到少量的胶原纤维,各肝纤维化组大鼠均可见肝组织呈明显的胶原纤维增生,且随着时间的延长,肝纤维化程度逐渐加重;免疫组织化学染色显示,对照组大鼠肝组织中可见极少量的BMP-7表达阳性的细胞,6周肝纤维化组大鼠可见较多的BMP-7阳性表达细胞,但随着实验时间的延长,BMP-7阳性细胞呈递减的趋势,至21周肝纤维化组大鼠肝组织中基本呈阴性表达;Western blotting 法检测大鼠肝组织BMP-7的表达结果与免疫组织化学的结果基本一致.结论 CC14诱导性肝纤维化大鼠肝组织BMP-7的表达与肝纤维化的程度呈负相关的趋势,推测BMP-7可能对肝纤维化具有一定的保护作用.

EXPRESSION OF BMP-7 IN HEPATIC TISSUE IN HEPATIC FIBROSIS RATS INDUCED BY CARBON TETRACHLORIDE

Objective To explore the relationship between the expression of BMP-7 in the hepatic tissue and hepatic fibrosis in rat hepatic fibrosis induced by CCl_4. Methods Healthy adult male Wistar rats were randomly divided into the control group and the hepatic fibrosis group.The control group was subcutaneously injected with oily solution of 0.12ml per 100 grams of rat weight every monday and thursday;the hepatic fibrosis group was subcutaneously injected with 60% carbon tetrachloride oily solution of 0.3ml per 100 grams of rat weight every monday and thursday.Rats were continuously injected for 6 weeks,10 weeks,16 weeks and 21weeks respectively.When the experiment ended,all the rats were killed.The hepatic middle lobule was taken and embedded with paraffin.Collagen fibers in the hepatic tissue were detected by Sirius red staining.The expression of BMP-7 in the hepatic tissue was detected by immunohistochemical staining and Western blotting. Results In the rat hepatic tissue,there were few collagen fibers in portal veins and the portal area in the control group.Proliferation of collagen fibers could be observed in each rat of the hepatic fibrosis group and hepatic fibrosis was aggravated with the lasting of the experiment.In immunohistochemical staining,several BMP-7 positive cells were observed in the rat livers of the control group; many BMP-7 positive cells were observed in the 6-week group.The expression of BMP-7 positive cells gradually decreased after 10 weeks,and they were seldom seen in the 21-week group.The Western blotting results were basically the same as those of immunohistochemical staining.Conclusion In rat hepatic fibrosis induced by carbon tetrachloride,the expression of BMP-7 in the hepatic tissue was opposite to that in the hepatic fibrosis.BMP-7 can protect the hepatic fibrosis to some degree.