脂联素对2型糖尿病大鼠主动脉内皮功能影响的研究

The effects of adiponectin on aortic endothelial function in type 2 diabetic rats

目的观察APN对T2DM大鼠主动脉内皮功能的影响。方法采用高脂饮食加腹腔注射STZ建立T2DM大鼠模型。造模成功后随机分为DM组9只和APN组8只,另设正常对照(NC)组10只。APN组给予尾静脉注射腺病毒重组APN(0.71×109 IU/只),DM组和NC组给予同等剂量生理盐水注射。测定各组胸主动脉内皮功能,核因子-κB(NF-κB)表达及一氧化氮(NO)水平。结果与DM组相比,APN组高敏C反应蛋白(hsC-RP)[(1.85±0.56)vs(3.13±0.38)mg/L]和丙二醛水平[(2.44±0.28)vs(4.80±0.59)mg/L]降低,APN水平[(273.50±21.20)vs(94.97±25.12)μg/L]升高(P<0.01)。NC组主动脉环最大舒张率高于其他两组[(81.7±5.2)%vs(65.9±9.9)%vs(36.0±8.9)%,P<0.05]。DM组主动脉NF-κB表达高于APN组和NC组,且APN组表达高于NC组(P<0.05)。NC组器官池中NO水平高于DM组和APN组[(125.6±17.7)vs(103.5±20.3)vs(72.5±9.1)μmol/g,P<0.05]。结论 APN能改善T2DM大鼠主动脉内皮功能,其机理可能与通过减少氧化应激和炎症反应,增加NO的产生有关。

Objective To investigate the protective effect of adiponectin on vascular endothelial dysfunction in streptozotocin-induced type 2 diabetic rat. Methods Diabetic rats were induced by high fat diet and intraperitoneal injection of a low dosd of STZ. After the model was established successfully, a total of 17 diabetic rats were randomly divided into DM group （n=9） and APN-treated DM group （n=8）. 10 normal rats were selected as control group （NC）.APN group was given intravenous injection of recombinant adenovirus adiponectin with 0. 71 × 109 IU in each rat. The same dose of saline was injected in DM group and NC group. The endothelial functions, nuclear factor-kB（NF-kB） expression and nitric oxide （NO） levels of thoracic aortas were measured. Results In APN group versus diabetic group, serum hsC- RP[（1. 85±0. 56） vs （3.13±0. 38） mg/L] and malondialdehyde levels[（2. 44±0. 28） vs （4. 80±0. 59） mg/L] were significantly lower,and serum adiponectin levels[（273.50±21.20） vs （94.97±25.12） /zg/L] was higher （all P〈0. 01）. The maximum relaxation rate of aortic ring was higher in NC group than in APN group or DM group [（81.7±5.2）%0 vs （65.9±9.9）% vs （36.0±8.9）%,P〈0.05]. The results of immunohistochemistry showed that the NF-xB expression in aorta was significantly higher in DM group than in NC group, and was decreased after treatment with adiponectin. Compared with NC group, NO level was significantly lower in diabetic rats, and was significantly increased after treatment with adiponectin [（125.6±17.7） vs （103.5±20. 3） vs （72.5±9.1）μmol/g,P〈0. 05]. Conclusion Adiponectin could protect the vascular endothelial function in type 2 diabetic rats. The mechanism may be explained by inhibiting oxidative stress, reducing inflammation,and increasing NO production.