【摘要】 目的:研究贯叶连翘提取物(HPE)对小鼠实验性免疫性心肌炎心肌纤维化(MFEAM)的影响。方法:利用猪心肌肌球蛋白免疫易感鼠系,建立小鼠MFEAM模型,将MFEAM模型组小鼠随机分为:MFEAM模型组(n=14)、HPE100 mg/kg组(n=13)、HPE 40 mg/kg组(n=13)、Cap 50 mg/kg对照组(n=13)。各组药物每次均分别以0.4 ml生理盐水溶解,采用灌胃给药方式,每天2次,共60 d;正常对照组(n=10),MFEAM模型组按上述方法同体积同疗程给予生理盐水。通过观察小鼠一般情况,测定心脏重量、脾脏重量与体重之比,检测小鼠血清中Ⅰ型前胶原N端前肽(PⅠNP)、Ⅲ型前胶原N端前肽(PⅢNP)含量及转化生长因子-β1(TGF-β1)浓度,Masson染色显微镜观察心肌纤维化(MF)程度及胶原容积分数(CVF)测定,Western blot检测心肌TGF-β1蛋白表达。结果:MFEAM模型组小鼠血清中TGF-β1浓度及PⅠNP、PⅢNP含量显著升高,MF程度及CVF增加,心肌TGF-β1蛋白表达上调,与正常组比较差异有显著性意义(P<0.05或P<0.01);而HPE 40 mg/kg、100 mg/kg及Cap对照组血清PⅠNP、PⅢNP含量及TGF-β1浓度均减少,不同HPE或Cap剂量显著改善或降低MFEAM模型小鼠MF程度及CVF,不同程度下调心肌TGF-β1蛋白表达水平,与MFEAM模型组比较差异有显著性意义(P<0.05或P<0.01)。结论:HPE对MF有治疗作用,可能与其减少胶原蛋白沉积,抑制TGF-β1信号通路有关。更多还原

【Abstract】 Objective: To study the effects of hypericum perforatum extract(HPE) on myocardial fibrosis of the experimental autoimmune myocarditis(MFEAM) in mice. Methods: MFEAM model of immunosuppressive mouse was established by porcine cardiac myosin. The mice in the MFEAM model group were randomly divided into: MFEAM model group(n = 14),HPE 100 mg/kg group(n= 13),HPE 40 mg/kg group(n = 13) and captopril(Cap) 50 mg/kg control group(n = 13). Drug in each group was dissolved in 0.4 ml of physiological saline each time,and administered by intragastric administration twice a day for 60 days; the normal control group(n= 10) and the MFEAM model group was given normal saline at the same volume and course of treatment as above described way.The ratio of heart weight and spleen weight to body weight were calculated,the general conditions of mice were observed. The contents of procollagen I N-terminal peptide(PⅠNP),procollagen ⅢN-terminal peptide(PⅢNP) and TGF-β1 in serum of mice were detected.The degree of myocardial fibrosis(MF) and collagen volume fraction(CVF) were measured under the microscope by Masson staining.The protein expression of TGF-β1 was detected by Western blot. Results: The serum levels of TGF-β1,PⅠNP and PⅢNP in the model group were higher than those in the normal group significantly(P<0.05 or P<0.01). Meanwhile,the levels of MF and CVF were increased,and the protein expression of myocardial TGF-β1 was up-regulated. However,the serum levels of PⅠNP,PⅢNP and TGF-β1 in HPE40 mg/kg,HPE 100 mg/kg and Cap treated-groups were decreased significantly. HPE and Cap could improve or decrease the MF level and CVF of the MFEAM model mice,and down-regulated the expression of TGF-β1 protein in different degrees. Compared with the MFEAM model group,the difference was significant(P<0.05 or P<0.01).Conclusion: HPE has a therapeutic effect on MF,which may be related to its reduction of collagen deposition and inhibition of TGF-β1 signaling pathway.更多还原