黄连素调节miRNA126及miRNA92a减轻糖尿病心肌梗死大鼠心肌损伤

Berberine Attenuates Myocardial Injury in Diabetic Rats with Myocardial Infarction by Modulating miRNA(126/92a)Expression

目的探讨黄连素对糖尿病心肌梗死大鼠心肌损伤的影响及其作用机制。方法糖尿病大鼠造模成功后将大鼠随机分为模型组及黄连素组,每组20只,另外20只健康大鼠作为对照组。再通过给糖尿病模型大鼠皮下注射异丙肾上腺素建立心肌梗死模型。黄连素组从糖尿病造模成功起灌胃黄连素口服(100 mg/kg),对照组及模型组不予干预。测定血清心肌损伤标记物肌酸磷酸激酶同工酶(CPK-MB)评估心肌梗死。HE染色观察心肌细胞改变。Western Blot检测CD31及血管内皮生长因子(VEGF)的蛋白水平。实时定量PCR法检测心肌miRNA126、miRNA92a的表达。结果模型组血清CPK-MB较对照组及黄连素组均显著升高(P<0.05)。HE染色发现,与模型组比较,黄连素组心肌细胞肥大和坏死的程度较轻,周围炎症较轻。与对照组比较,模型组CD31、VEGF表达增加,miRNA126、miRNA92a水平降低(P<0.05)。与模型组比较,黄连素组CD31、VEGF表达更高,miRNA126、miRNA92a水平更低(P<0.05)。结论黄连素可减轻糖尿病心肌梗死大鼠的心肌损伤程度,促进损伤局部新生血管形成,其机制可能是通过下调miRNA126及miRNA 92 a的表达来实现的。

Objective To determine the effect of berberine on myocardial injury in diabetic rats with myocardial infarction and to explore the underlying mechanisms.Method After successful establishment of diabetic rats,rats were randomly divided into model group and berberine group,20 rats in each group,and another 20 healthy rats were collected as control group.Myocardial infarction model was established by subcutaneous injection of isoproterenol in diabetic rats.Berberine group was given berberine by intragastrical gavage(100 mg/kg)from the successful modeling of diabetes mellitus,the control group and model group were not interfered.MB isoenzyme of creatine phosphokinase(CPK-MB)in serum was used to evaluate myocardial infarction.The changes of myocardial cells were observed by HE staining.The protein levels of CD31 and vascular endothelia growth factor(VEGF)were detected by Western Blot.The expression of miRNA126 and miRNA92a were detected by real-time PCR.Results Serum CPK-MB in model group was significantly higher than that in control group and berberine group(P<0.05).Compared with model group,the degree of cardiac myocyte hypertrophy and necrosis in berberine group was less.Compared with control group,the expression of CD31 and VEGF in model group were significantly increased,while the expression of miRNA126 and miRNA92a in myocardial infarction area decreased(P<0.05).Compared with model group,the expression of CD31 and VEGF in berberine group were significantly higher,while the expression of miRNA126 and miRNA92a in myocardial infarction area of berberine group were lower(P<0.05).Conclusions Berberine could reduce myocardial injury and promote local angiogenesis in diabetic myocardial infarction rats.The mechanism may be by down-regulating the expression of miRNA126 and miRNA92a.