淫羊藿苷通过调控α-SMA和MMPs/TIMP的表达改善异丙肾上腺素所诱导的心肌纤维化

Icariin improves myocardial fibrosis induced by isoproterenol via regulating expression ofα-SMA and MMPs/TIMP

目的探讨淫羊藿苷(icariin,ICA)对异丙肾上腺素(ISO)诱导的心肌纤维化的干预作用。方法将C57BL/6小鼠,随机分为空白组、ISO模型组、ICA低、中、高剂量组(15、30、60 mg·kg^(-1))和氯沙坦组(9 mg·kg^(-1))。空白组注射生理盐水,其余连续14 d皮下注射ISO(5 mg·kg^(-1),qd)制备心肌纤维化模型。同时,ICA和氯沙坦组灌胃给予ICA或氯沙坦,其余灌胃等体积双蒸水。采用小动物超声仪检测小鼠左心室射血分数(LVEF)和左心室短轴缩短率(LVFS);计算心脏质量指数(HMI);Masson染色观察左心室胶原沉积;Western blot检测左心室组织α-SMA、MMP-2、MMP-9和TIMP-1蛋白的表达。结果ICA(30、60 mg·kg^(-1))和氯沙坦可抑制ISO所致的小鼠LVEF和LVFS的降低,HMI的升高,左心室胶原沉积的增加,左心室组织α-SMA、MMP-9蛋白表达的上调及MMP-2、TIMP-1蛋白表达的下调(P<0.05)。结论ICA能够改善ISO诱导的小鼠心肌纤维化,其机制至少可能与调控α-SMA、MMPs/MMP-1的蛋白表达有关。

Aim To explore the effect of icariin(ICA)on myocardial fibrosis induced by isoproterenol(ISO)in mice.Methods C57BL/6 mice were randomly divided into control group,ISO group,low-dose(15 mg·kg^(-1)),middle-dose(30 mg·kg^(-1))and high-dose(60 mg·kg^(-1))of ICA-treated group and Losartan-treated group(9 mg·kg^(-1)).The control group was subcutaneously injected with normal saline,and the other groups were subcutaneously injected with ISO(5 mg·kg^(-1),qd)continuously 14 days to established the myocardial fibrosis model.The ICA-treated groups and Losartan-treated group were simultaneously intragastrically administered of ICA or Losartan,respectively.And the other groups received the same amount of double distilled water.The left ventricular ejection fraction(LVEF)and the left ventricular fraction shortening rate(LVFS)were evaluated by the small animal ultrasound.The heart mass index(HMI)was calculated.The left ventricular collagen deposition was detected by Masson staining.The protein expressions ofα-SMA,MMP-2,MMP-9 and TIMP-1 in the left ventricular tissue were detected by Western blot.Results ICA(30,60 mg·kg^(-1))and Losartan could inhibit the decreased LVEF and LVFS,the increased HMI and left ventricular collagen deposition,the up-regulatedα-SMA and MMP-9 protein expression,the down-regulated MMP-2 and TIMP-1 protein expression in the left ventricular tissues induced by ISO.Conclusions ICA can improve myocardial fibrosis induced by ISO in mice,and the underlying mechanism may be related to the regulation of the protein expression ofα-SMA and MMPs/TIMP-1.