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目的探讨p38丝裂素活化蛋白激酶(MAPK)与糖尿病大血管病变的关系及利拉鲁肽对其的干预作用。方法 24只Wistar大鼠分为正常对照组(NC)和实验组(EXP)。EXP组予高糖高脂饮食联合小剂量STZ腹腔注射建立T2DM大鼠模型。将成模大鼠随机分为糖尿病组(DM)和利拉鲁肽组(LIR),每组各7只。LIR组予利拉鲁肽(100μg/kg,2次/d)皮下注射,共8周;DM组和NC组予等量生理盐水皮下注射。实验结束后,测定各组相关指标;HE染色观察胸主动脉形态,免疫组织化学法检测胸主动脉磷酸化p38MAPK、核因子-κB(NF-κB)和单核细胞趋化蛋白-1(MCP-1)蛋白表达水平。结果 HE染色可见DM组胸主动脉呈动脉粥样硬化表现。DM组胸主动脉磷酸化p38MAPK、NF-κB和MCP-1蛋白表达水平较NC组升高(P=0.000),LIR组较DM组降低(P=0.017)。Spearman相关分析显示,胸主动脉磷酸化p38 MAPK与NF-κB、MCP-1蛋白表达呈正相关。DM组血糖、TG、TC、LDL-C、血清细胞间黏附分子-1(ICAM-1)、血管内皮黏附分子-1(VCAM-1)、NF-κB水平较NC组升高(P=0.000),较LIR组降低(P<0.01)。结论在大鼠实验中,p38MAPK信号通路参与了糖尿病大血管病变的发生;利拉鲁肽可能通过下调血管p38MAPK磷酸化水平、抑制炎症反应、调脂等发挥了对糖尿病大血管病变的保护作用。
Objective To investigate the relationship between p38 mitogen-activated protein kinase (MAPK) and diabetic macroangiopathy and the effect of liraglutide on it. Methods Twenty-four Wistar rats were divided into normal control group (NC) and experimental group (EXP). In the EXP group, T2DM rat model was established by intraperitoneal injection of high-sugar and high-fat diet combined with low-dose STZ. The rats were randomly divided into diabetic group (DM) and liraglutide group (LIR), each group of seven. LIR group received liraglutide (100μg / kg twice a day) subcutaneously for 8 weeks. The rats in DM group and NC group were injected subcutaneously with normal saline. At the end of the experiment, the relative indexes of each group were determined. The morphology of the thoracic aorta was observed by HE staining. The phosphorylated p38MAPK, NF-κB and monocyte chemoattractant protein-1 (MCP-1) in the thoracic aorta were detected by immunohistochemical staining -1) protein expression level. Results HE staining showed that the thoracic aorta showed atherosclerosis in DM group. The phosphorylation of p38MAPK, NF-κB and MCP-1 in thoracic aorta in DM group were significantly higher than those in NC group (P = 0.000). LIR group was lower than DM group (P = 0.017). Spearman correlation analysis showed that the phosphorylation of p38 MAPK in thoracic aorta was positively correlated with the expression of NF-κB and MCP-1. The level of blood glucose, TG, TC, LDL-C, ICAM-1, VCAM-1 and NF-κB in DM group were higher than those in NC group ), Lower than LIR group (P <0.01). Conclusion In the rat experiment, p38MAPK signaling pathway is involved in the development of diabetic macroangiopathy. Liraglutide may play a protective effect on diabetic macroangiopathy by downregulating the phosphorylation of p38MAPK, inhibiting the inflammatory reaction and regulating lipid metabolism.