基于p38MAPK通路探讨丹蛭降糖胶囊对2型糖尿病模型大鼠血管病变的影响

目的:基于p38丝裂原活化蛋白激酶(p38MAPK)信号通路观察丹蛭降糖胶囊对实验性2型糖尿病(T2DM)模型大鼠血管内皮功能受损的影响。方法:采用高脂高糖饮食及腹腔注射链脲佐菌素(STZ)建立T2DM大鼠模型,将104只大鼠随机分成正常组,模型组,丹蛭降糖胶囊高、中、低剂量(1.08,0.72,0.54 g·kg^-1·d^-1)组,吡格列酮(10 mg·kg^-1·d^-1)组,丹蛭-吡格列酮(1.08+0.01 g·kg^-1·d^-1)组。造模成功后分别按相应剂量ig药物,每日1次。给药8周后,所有大鼠麻醉后腹主动脉采集血液样本和处死剪取腹主动脉进行相关检测,分析其作用机制。结果:治疗8周后,与正常组相比,模型组磷酸化p38丝裂原活化蛋白激酶(p-p38MAPK),MAPK激酶3/6(MKK3/6),核转录因子cAMP反应元件结合蛋白1(CREB1),环氧化酶-2(COX-2),细胞间黏附分子(ICAM-1)蛋白表达水平均有上调,丝裂原活化蛋白激酶磷酸酶-1(MKP-1)蛋白表达水平下调;与模型组相比,给药组大鼠p-p38MAPK,MKK3/6,CREB1,COX-2,ICAM-1蛋白表达水平均有下调,MKP-1蛋白表达水平明显上调(P<0.05,P<0.01)。腹主动脉免疫组化示,给药组p38MAPK蛋白表达量与模型组相比明显降低。结论:丹蛭降糖胶囊能调节T2DM模型大鼠血管p38MAPK蛋白表达水平,并可能从而改善大鼠血管内皮功能受损。

Effect of Danzhi Jiangtang Capsule on Vasculopathy of Type 2 Diabetes Mellitus Rat Models Based on p38MAPK Pathway

Objective: To observe the effects of Danzhi Jiangtang capsules on impaired endothelial function in rats models with type 2 diabetes mellitus (T2DM) based on p38 mitogen-activated protein kinase (p38MAPK) signal pathways. Method: High fat and high glucose diet and intraperitoneal injection of streptozotocin (STZ) were used to establish T2DM rat models. One hundred and four rats were randomly divided into 7 groups:normal group, model group, Danzhi Jiangtang capsule high, medium, low dose groups (1.08, 0.72, 0.54 g·kg^-1·d^-1), pioglitazone group (10 mg·kg^-1·d^-1), integrated Danzhi and pioglitazone group (1.08 g·kg^-1·d^-1+10 mg·kg^-1·d^-1). After successful modeling, the diabetic model rats were respectively ig given with corresponding dose of medicines, once a day. After 8 weeks of treatment, blood samples and abdominal aorta were collected to do correlation detection after rats anesthesia, and their mechanism of action was analyzed. Result: After 8 weeks of treatment, compared with the normal group, p-p38 mitogen activated protein kinase(p-p38MAPK), mitogen activated protein kinase kinasse3/6(MKK3/6), cAMP response element-bingding protein(CREB1), cyclooxygenase2(COX-2), and intercellular cell adhesion molecule-1(ICAM-1) protein expression levels were increased in model group;mitogen-activated protein kinase phosphatase-1(MKP-1) protein expression level was reduced in the model group. Compared with the model group, p-p38MAPK, MEK3/6, CREB1, COX-2, and ICAM-1 protein expression levels were reduced, and MKP-1 protein expression levels were increased in treatment groups (P<0.05, P<0.01). The abdominal aorta immunohistochemistry showed that compared with the model group, the expression level of p38MAPK was significantly decreased in the treatment groups. Conclusion: Danzhi Jiangtang capsule can regulate the expression level of vascular p38MAPK protein in T2DM rat models and may thus improve the impaired endothelial function in rats.