通心络胶囊对糖尿病心肌病小鼠的心脏保护作用

Cardiac Protective Effects of Tongxinluo Capsule on Diabetic Cardiomyopathy Mice

目的观察通心络胶囊调控p38丝裂原活化蛋白激酶(p38 mitogen-activated protein kinases,p38 MAPK)炎症信号通路对糖尿病心肌病小鼠防治作用。方法 KK/Upj-Ay小鼠40只随机分为模型组和通心络低、中、高剂量组,每组10只,另设C57BL/6小鼠10只作为对照组。各组给予相应药物,疗程为12周,观察体质量,测定空腹血糖(fasting blood glucose,FBG)、糖化血红蛋白(hemoglobin A1c,Hb A1c)、甘油三酯(triglyceride,TG)、总胆固醇(total cholesterol,TC)、左心室指数;放射免疫法测定各组血清肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白介素-6(interleukin-6,IL-6)含量;HE染色观察心肌组织病理变化;Western blot法检测心肌组织p38 MAPK、c-Jun氨基末端激酶(c-Jun N-terminal kinase,JNK)、细胞外信号调节激酶(extracellular-signa1 regulated kinase,ERK)总蛋白及磷酸化p38 MAPK、JNK、ERK(p-p38 MAPK、p-JNK、p-ERK)的表达。结果与对照组比较,模型组FBG、Hb A1c、TG、TC、左心室指数、TNF-α、IL-6及p-p38MAPK、p-JNK、p-ERK表达均显著增高,通心络胶囊能够减轻心肌组织病理损伤,降低TG、TC、TNF-α、IL-6含量及p-p38MAPK、表达,而不影响体质量、FBG、Hb A1c及p-JNK、p-ERK表达;且各组p38 MAPK、JNK、ERK总蛋白表达无统计学意义。结论通心络胶囊可减轻糖尿病心肌病理损伤,改善心功能,其机制可能与降低p38 MAPK蛋白磷酸化水平,抑制炎症反应有关。

OBJECTIVE To explore the effects of Tongxinluo capsule on p38 mitogen-activated protein kinase（p38 MAPK） inflammatory signal pathway in mice with diabetic cardiomyopathy. METHODS Forty KK/Upj-Ay mice were randomly divided into model group and Tongxinluo（low, middle, high） groups（n=10, respectively）. C57BL/6 mice were selected as control group（n=10）. After 12 weeks, the mice were sacrificed and were weighed. The fasting blood-glucose（FBG）, glycosylated hemoglobin（Hb A1c）, triglyceride（TG）, total cholesterol（TC） and left ventricular index were measured. Radioimmunoassay was used to measure the contents of serum tumor necrosis factor-α（TNF-α） and interleukin-6（IL-6）. The pathological changes in the myocardium of mice were observed by HE staining. The expression levels of total p38 MAPK, phosphorylated p38 MAPK（p-p38 MAPK）, total c-Jun N-terminal kinase（JNK）, phosphorylated JNK（p-JNK）, total extracellular-signa1 regulated kinase（ERK）, phosphorylated ERK（p-ERK） were detected by Western blot. RESULTS Compared with the control group, the level of FBG, Hb A1 c TG, TC, TNF-α and IL-6, left ventricular weight index, and the expression of p-p38 MAPK, p-JNK, p-ERK in the model group were higher. Tongxinluo capsule reduced myocardium pathological damage and the level of TG, TC, TNF-α and IL-6, and down-regulated the expression of p-p38 MAPK in myocardium of diabetic mice, but had no effects on body weight, FBG, Hb A1 c and the expression of p-JNK, p-ERK. The total expression of p38 MAPK, JNK and ERK proteins among four groups had no significant difference. CONCLUSION Tongxinluo capsule can ameliorate the myocardium damage and improve the function of diabetic myocardium by down-regulating the phosphorylation of p38 MAPK and inhibiting the inflammation reaction.