瘦素对大鼠肝纤维化的信号转导调控及槲寄生碱的干预作用

发布时间：2018-11-21 14:28

【摘要】：目的探讨瘦素调控大鼠肝纤维化的信号转导机制及槲寄生碱的干预作用。方法以CCl4诱导的肝纤维化大鼠模型为研究对象,45只大鼠随机分为三组,分别为对照组、模型组、药物干预组。对照组不做任何处理,自由饮食、饮水;模型组和槲寄生碱治疗组分别腹腔注射40%CCl4-植物油溶液2 m L/kg,每周2次,共8周。实验第9周,治疗组经灌胃给予大鼠槲寄生碱8g/(kg·d),模型组灌胃给予等剂量的生理盐水,共8周。实验第17周颈椎脱臼法处死所有动物,取出肝脏左前叶。采用HE染色、MASSON染色方法观察槲寄生碱对肝纤维化大鼠肝组织形态学的影响;免疫组织化学的方法观察槲寄生碱对大鼠肝星状细胞瘦素及瘦素受体的影响。Western Blot法检测大鼠肝脏组织JAK2、STAT3蛋白水平以及JAK2、STAT3蛋白磷酸化水平。结果肝脏大体、HE染色以及Masson胶原染色结果提示:大鼠肝纤维化模型复制成功,槲寄生碱具有阻断逆转肝纤维化的作用。免疫组织化学染色显示,与模型组比较,槲寄生碱明显抑制模型大鼠肝组织瘦素、瘦素受体的表达。Western Blot显示,正常对照组JAK2、STAT3蛋白表达量最少;模型组JAK2、STAT3蛋白高表达;而药物处理组的JAK2、STAT3蛋白表达明显下调。结论槲寄生碱可有效逆转大鼠肝脏纤维化,其作用机制可能是通过下调大鼠肝组织瘦素、瘦素受体的表达,进而影响JAK2/STAT3信号通路来完成的。
[Abstract]:Objective To study the signal transduction mechanism and the intervention effect of leptin in the control of hepatic fibrosis in rats. Methods The model of hepatic fibrosis induced by CCl4 was studied. Forty-five rats were randomly divided into three groups: control group, model group and drug intervention group. The control group did not do any treatment, the free diet, the drinking water, the model group and the mistletoe treatment group were respectively injected with 40% CCl4-vegetable oil solution 2 ml/ kg, twice a week for 8 weeks. In the 9th week of the experiment, the treated group was given a total of 8g/ (kg 路 d) of mistletoe in rats, and the model group was given an equal dose of normal saline for 8 weeks. All animals were sacrificed at the 17-week cervical dislocation, and the left anterior lobe of the liver was removed. The effect of mistletoe on the morphology of hepatic fibrosis in rats with hepatic fibrosis was observed by HE staining and MASSON staining. The effect of mistletoe on the leptin and leptin receptor in rat hepatic stellate cells was observed by immunohistochemistry. The levels of JAK2, STAT3 protein and JAK2 and STAT3 protein were detected by Western Blot method. Results The results suggested that the liver fibrosis model of the rat was successful, and the mistletoe had the effect of blocking and reversing the hepatic fibrosis. Immunohistochemistry staining showed that the mistletoe significantly inhibited the expression of leptin and leptin receptor in the model rats compared with the model group. Western Blot showed that the expression of JAK2 and STAT3 in the normal control group was the least; the expression of JAK2 and STAT3 in the model group was significantly lower; and the expression of JAK2 and STAT3 in the drug-treated group was significantly reduced. Conclusion The mistletoe can effectively reverse the rat liver fibrosis, and the mechanism of action may be accomplished by down-regulating the expression of leptin and leptin receptor in rat liver tissue, and further affecting the signal pathway of JAK2/ STAT3.
【作者单位】：首都医科大学实验动物部;首都医科大学病理生理教研室;
【基金】：国家自然科学基金资助项目(81272757) 北京市属高等学校创新团队建设与教师职业发展计划项目(IDHT20150502)
【分类号】：R575.2

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