缬沙坦对2型糖尿病大鼠血管功能损伤的保护作用

Protective effects of valsartan against vasodilatation function injury in type 2 diabetic rats

目的观察缬沙坦对2型糖尿病大鼠离体胸主动脉、肾动脉、肠系膜动脉舒张功能的保护作用并分析其机制。方法使用雄性大鼠36只随机分为2组，即正常对照组和糖尿病组。糖尿病组给予高糖高脂饮食诱导结合＋STZ注射（40mg／kg体重）制备2型糖尿病模型。造膜成功后随机分为糖尿病＋盐水组和糖尿病＋缬沙坦组，分别给予相应体积生理盐水或缬沙坦10mg·kg-1·d-1灌胃，持续8周后，处死动物取胸主动脉、肾动脉和肠系膜动脉，检测各组血管内皮依赖和非内皮依赖性舒张反应及血管生物化学指标。结果与正常对照组相比，糖尿病＋盐水组大鼠各血管内皮依赖性舒张功能显著下降，表现为Emax值下降和EC50显著升高，糖尿病＋缬沙坦治疗组与糖尿病＋盐水对照组相比，血管内皮依赖性舒张功能显著改善，而硝普钠诱导的非内皮依赖性舒张反应三组差异无统计学意义。自由基测定结果表明，糖尿病引起血管组织发生自由基损伤，表现为丙二醛含量升高，超氧化物歧化酶活性降低，同时一氧化氮含量下降，舒血管功能受损。缬沙坦干预使一氧化氮生成增加，自由基损伤减轻，显著改善了糖尿病造成的血管损伤。结论缬沙坦对2型糖尿病大鼠的胸主动脉、肾动脉及肠系膜动脉的内皮依赖性舒张功能受损均有显著保护作用，作用与其抗自由基生成、促进内皮一氧化氮合成有关。

Objective To observe the effects of valsartan on endothelium dependent vasodilatation of thoracic aorta, renal artery and mesenteric artery in type 2 diabetic rats, the mechanism was also analyzed, nethotis 36 male wistar rats were randomly divided into 3 groups, normal control group, diabetes plus saline group （saline 10 ml^kg-~＇d-1, irrigation stomach）, diabetes plus valsartan treatment group （valsartan 10 mg^kgq^d-l, irrigation stomach）. Type 2 diabetes was induced by high glucose and high fat diet plus streptozocin 50 mg/kg in- traperitoneal injection. All rats were sacrificed 8w after injection, plasma and thoracic aorta, renal artery, mesen- teric artery were collected for further experiment. The aeetylcholine induced endothelium dependent vasodilatation and sodium Nitroprusside induced endothelium independent vasodilatation was observed. Results Compared with the normal control group, diabetes plus saline group showed severe impairment of endotbelium dependent vasodila- tive action, while have no influence on endothelium independent vasodilative action （P〈0.05）. Valsartan treatment for 8w improved the endothelium dependent vasodilative function significantly without change of blood glucose level. Further detemination of vascular MDA content, SOD activity and nitric oxide （NO） content exhibited severe reac- tive oxygen species injury and reduced NO production in diabetes plus saline group, while valsartan treatment ameliorated diabetes induced reactive oxygen species injury and NO decrease （P〈0.05）. Conclusion Valsartan can protect the endothelium dependent vasodilatation of thoracic aorta, renal artery and mesenteric artery against type 2 diabetic induced vascular injury. The protection is exerted partly by its effects of reducing reactive oxygen species injury and incresing NO production.