心康冲剂调控慢性心衰大鼠miRNA-21/PTEN抗心肌纤维化研究

Effect of Xinkang Granule on Anti-Myocardial Fibrosis by Regulating miRNA-21/PTEN in Rats with Chronic Heart Failure

目的探讨心康冲剂抗心衰大鼠心肌纤维化的机制。方法90只SD大鼠分为正常组10只,模型组、对照组及心康低、中、高剂量组各16只。心康低、中、高剂量组分别给予0.5、1、2 g/(kg·d)的心康冲剂溶液。对照组给予0.06 g/(kg·d)的芪苈强心胶囊。正常组、模型组按1 m L/(kg·d)灌服生理盐水。各组均每日1次,连续灌服8周。计算左心室质量指数(LVMI);心脏切片行HE、Masson染色并计算胶原容积分数(CVF);采用Real-time PCR法检测miRNA-21、人第10号染色体缺失的磷酸酶及张力蛋白同源基因(PTEN)m RNA表达水平;用Pearson相关及Logistic多元线性回归分析miRNA-21、PTEN m RNA、CVF与LVMI之间的相关性。结果与正常组比,模型组大鼠心肌CVF、LVMI比值及miRNA-21表达升高(P<0.01),PTENm RNA表达下降(P<0.01)。与模型组比,心康低、中、高剂三组CVF、LVMI比值及miRNA-21表达下降(P<0.01)、PTENm RNA表达升高(P<0.01);与芪苈强心组比较,心康冲剂低、中、高剂LVMI、CVF、miRNA-21、PTEN m RNA无明显差异(P>0.05)。miRNA-21、PTENm RNA、CVF均与LVMI有明显线性相关关系。结论心康冲剂可通过下调miRNA-21、升高PTEN m RNA表达抗心肌纤维化。

Objective To explore the mechanism of Xinkang Granule on anti-myocardial fibrosis in rats with heart failure.Methods Ninety SD rats were randomly divided into normal group(n=10),model group(n=16),control group(n=16),XKG low-dose group(n=16),XKG middle-dose group(n=16),XKG high-dose group(n=16).Xinkang groups were given with 0.5,1,2 g/(kg·d)Xinkang granule solution.The control group was given with 0.06 g/(kg·d)Qiliqiangxin capsule(QLQXC).Rats in the normal group and model control group were administrated with saline at 1 mL/(kg·d).Every group was given corresponding medicine by gavage for 8 weeks,once daily.The left ventricular mass index(LVMI)was calculated.The slice of heart was stained by HE and Masson,and collagen volume fraction(CVF)of heart was caculated.The expression levels of miRNA-21,phosphatase and tensin homology gene deleted on chromosome ten(PTEN)were measured by Real-time PCR method.The correlations between miRNA-21,PTEN mRNA,CVF and LVMI were analyzed by Pearson correlation and Logistic multivariate linear regression.Results Compared with the normal group,CVF,LVMI and the expression of miRNA-21 in rats of the model group increased(P<0.01),and PTEN mRNA down-regulated(P<0.01).Compared with the model group,CVF,LVMI and the expression level of miRNA-21 in rats of Xinkang groups down-regulated(P<0.01),and PTEN mRNA up-regulated(P<0.01).Compared with QLQXC group,the LVMI,CVF,miRNA-21,PTEN mRNA in all Xinkang granule groups were not statistically significant(P>0.05).MiRNA-21,PTEN mRNA and CVF showed obvious linear correlation with LVMI.Conclusion Xinkang granule showed anti-myocardial fibrosis effect by down-regulating miRNA-21 and increasing PTEN mRNA expression.