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目的:观察益气活血方对糖尿病大鼠基于p38丝裂原活化的蛋白激酶(p38MAPK)信号通路对血管内皮功能受损的综合调节作用机制。方法:采用高脂高糖饮食和应用链脲佐菌素(STZ)建立大鼠糖尿病模型,将大鼠随机分成7组,分别为正常组,模型组,丹蛭降糖胶囊高、中、低剂量组(1.08,0.72,0.54 g·kg-1·d-1),盐酸吡格列酮胶囊组(10 mg·kg-1·d-1),丹蛭降糖胶囊+盐酸吡格列酮胶囊结合组(1.08 g·kg-1·d-1+10 mg·kg-1·d-1)。大鼠造模成功后分别按相应剂量药物ig给予,每日1次,连续8周,后腹主动脉采集血液样本和腹主动脉进行相关检测,蛋白质免疫印迹(Western blot)法测定p38MAPK,上游MAPK激酶3/6(mitogen activated protein kinase kinasse3/6,MKK3/6),下游核转录因子c AMP反应元件结合蛋白1(c AMP response element-bingding protein,CREB1)以及其丝裂原活化蛋白激酶磷酸酶-1(mitogen-activated protein kinase phosphatase-1,MKP-1)信号蛋白在内皮细胞的蛋白表达量;实时荧光定量聚合酶链式反应(q PCR)方法测定单核细胞趋化蛋白-1(MCP-1),血管内皮细胞抵抗素在血管内皮中的mRNA表达。结果:与正常组比较,模型组p38MAPK,MKK3/6,CREB1蛋白及MCP-1,血管内皮细胞抵抗素mRNA表达水平明显升高(P<0.01),MKP-1蛋白表达水平明显降低(P<0.01);各给药组p38MAPK,MKK3/6,CREB1蛋白及MCP-1,血管内皮细胞抵抗素mRNA表达水平均明显降低,MKP-1蛋白表达水平均明显升高,与模型组大鼠比较差异均有统计学意义(P<0.05)。结论:益气活血方通过调节糖尿病大鼠血管p38MAPK信号通路蛋白表达水平,从而达到降低血管内皮功能损伤的作用。
AIM: To observe the mechanism of Yiqi Huoxue decoction on p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway in vascular endothelial dysfunction in diabetic rats. Methods: Diabetic rats were induced by high-fat and high-sugar diet and streptozotocin (STZ). The rats were randomly divided into 7 groups: normal group, model group, high, medium and low Dose group (1.08,0.72,0.54 g · kg-1 · d-1), pioglitazone hydrochloride capsule group (10 mg · kg-1 · d-1), danzhitang capsule + pioglitazone hydrochloride capsule combination group · Kg -1 · d -1 +10 mg · kg -1 · d -1). After successful model establishment, rats were given the corresponding doses of ig once a day for 8 weeks. The blood samples collected from the abdominal aorta and the abdominal aorta were detected. Western blot was used to determine the expression of p38MAPK. MAPK kinase 3/6 (mitogen activated protein kinase kinasse3 / 6, MKK3 / 6), c AMP response element-bingding protein (CREB1) and its mitogen-activated protein kinase The protein expression of mitogen-activated protein kinase phosphatase-1 (MKP-1) in endothelial cells was detected by real-time fluorescence quantitative polymerase chain reaction (qPCR) MCP-1), mRNA expression of vascular endothelial resistin in vascular endothelium. Results: Compared with the normal group, the expressions of p38MAPK, MKK3 / 6, CREB1 and MCP-1 and resistin in the model group were significantly increased (P <0.01) and the expression of MKP- 0.01). The expression of p38MAPK, MKK3 / 6, CREB1 protein and MCP-1 and vascular endothelial cell resistin mRNA were significantly decreased and the expression of MKP-1 protein were significantly increased in each treatment group compared with the model group All were statistically significant (P <0.05). Conclusion: Yiqi Huoxue Fang can reduce the damage of vascular endothelial function by regulating the expression of p38MAPK signal pathway protein in blood vessels of diabetic rats.