心康冲剂调控慢性心衰大鼠miRNA-21/PTEN抗心肌纤维化研究

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 mL/（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）mRNA表达水平；用Pearson相关及Logistic多元线性回归分析miRNA-21、PTEN mRNA、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），PTENmRNA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）、PTENmRNA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 mRNA无明显差异（P>0.05）。miRNA-21、PTENmRNA、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 mRNA表达抗心肌纤维化。

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

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.