激动κ阿片受体对糖尿病大鼠血管舒缩功能及结构的影响

目的研究激动κ阿片受体(KOR)对糖尿病大鼠肠系膜小动脉血管舒缩功能及主动脉结构的影响,探讨其作用机制。方法选取雄性SD大鼠40只,分为对照组(16只)和模型组(24只)。其中,对照组分为正常组和正常+U50,488H组(U50,488H 1组),每组8只;模型组分为糖尿病组、糖尿病+U50,488H组(U50,488H 2组)和糖尿病+nor-BNI组(nor-BNI组),每组8只。采用体外血管环灌流技术检测肠系膜小动脉血管舒缩功能;Westernblot法检测小动脉血管组织内皮型一氧化氮合酶(eNOS)、NF-κB及KOR表达水平;光镜HE染色观察主动脉结构变化。结果与正常组比较,糖尿病组对KCl和去甲肾上腺素引起的收缩反应明显增强(P0.05),对乙酰胆碱引起的舒张反应明显减弱(P0.05),对硝普钠引起的舒张反应无明显变化;eNOS表达减少,而NF-κB及KOR表达增加(P0.01)。U50,488H处理后,eNOS及KOR表达增加而NF-κB表达减少;nor-BNI处理后,eNOS及KOR表达减少而NF-κB表达增加(P0.01)。结论激动KOR可改善糖尿病大鼠肠系膜小动脉血管舒缩功能和主动脉结构,机制可能与通过增加eNOS表达改善内皮功能和通过抑制NF-κB表达降低炎症水平有关。

Effects of activating kappa opioid receptors on the arterial vasomotoricity and the aortic structure of diabetic rats

Objective To investigate the effects of activating kappa opioid receptors(KOR) on the mesenteric arterial vasomotoricity and the aortic structure of diabetic (DM) rats.Methods The model of DM rats was set and U50,488H or nor-BNI was given separately.Vasomotoricity was evaluated with mesenteric arterial rings;protein expression of eNOS,NF-κB and KOR was analyzed by Western blot.Changes of aortic structure were observed by light microscopy.Results In DM rats,the vasomotoricity of mesenteric arterial rings was significantly abnormal compared with control rats (P <0.05) ;the protein expression of eNOS decreased and the protein expression of NF-κB and KOR increased (P < 0.01) ;the aortic structure showed signs of disorder obviously. U50,488H treatment alleviated the disorder of mesenteric arterial vasomotoricity and aortic structure, decreased the expression of NF-kB and up-regulated the level of eNOS and KOR,while nor-BNI worked oppositely.Conclusions Activating KOR can alleviate the abnormality of mesenteric arterial vasomotoricity and aortic structure in diabetic rats by improving endothelial function and decreasing chronic inflammation.