【摘要】：目的探討瘦素調控大鼠肝纖維化的信號轉導機制及槲寄生堿的干預作用。方法以CCl4誘導的肝纖維化大鼠模型為研究對象,45只大鼠隨機分為三組,分別為對照組、模型組、藥物干預組。對照組不做任何處理,自由飲食、飲水;模型組和槲寄生堿治療組分別腹腔注射40%CCl4-植物油溶液2 m L/kg,每周2次,共8周。實驗第9周,治療組經灌胃給予大鼠槲寄生堿8g/(kg·d),模型組灌胃給予等劑量的生理鹽水,共8周。實驗第17周頸椎脫臼法處死所有動物,取出肝臟左前葉。采用HE染色、MASSON染色方法觀察槲寄生堿對肝纖維化大鼠肝組織形態(tài)學的影響;免疫組織化學的方法觀察槲寄生堿對大鼠肝星狀細胞瘦素及瘦素受體的影響。Western Blot法檢測大鼠肝臟組織JAK2、STAT3蛋白水平以及JAK2、STAT3蛋白磷酸化水平。結果肝臟大體、HE染色以及Masson膠原染色結果提示:大鼠肝纖維化模型復制成功,槲寄生堿具有阻斷逆轉肝纖維化的作用。免疫組織化學染色顯示,與模型組比較,槲寄生堿明顯抑制模型大鼠肝組織瘦素、瘦素受體的表達。Western Blot顯示,正常對照組JAK2、STAT3蛋白表達量最少;模型組JAK2、STAT3蛋白高表達;而藥物處理組的JAK2、STAT3蛋白表達明顯下調。結論槲寄生堿可有效逆轉大鼠肝臟纖維化,其作用機制可能是通過下調大鼠肝組織瘦素、瘦素受體的表達,進而影響JAK2/STAT3信號通路來完成的。
[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.
【作者單位】： 首都醫(yī)科大學實驗動物部;首都醫(yī)科大學病理生理教研室;
【基金】：國家自然科學基金資助項目(81272757) 北京市屬高等學校創(chuàng)新團隊建設與教師職業(yè)發(fā)展計劃項目(IDHT20150502)
【分類號】：R575.2

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