α-硫辛酸对糖尿病大鼠体外循环后认知功能的影响

Effect of a-lipoic acid on cognitive function after cardiopuimonary bypass in diabetic rats

目的评价α-硫辛酸对糖尿病大鼠体外循环（CPB）后认知功能的影响。方法成年雄性SD大鼠，体重400～450g，16～22周龄，腹腔注射1％链脲佐菌素60mg／kg建立糖尿病模型。取糖尿病模型制备成功的大鼠32只，采用随机数字表法，将其随机分为2组（n=16）：糖尿病组（D组）和α-硫辛酸组（L组）。L组在糖尿病模型建立后第6周腹腔注射α-硫辛酸30mg／kg，1次／d，连续7d，D组给予等容量生理盐水。2组于停止腹腔给药后进行CPB。分别于糖尿病模型建立前、糖尿病模型建立后第5周、CPB模型建立前、CPB结束时、CPB停止后3d及CPB停止后5d时取10只大鼠，采集静脉血样，测定血浆TNF-α及IL-10的浓度；分别于糖尿病模型建立前、CPB模型建立前和CPB停止后5d时取10只大鼠，测定认知功能，认知功能测试后处死，取海马组织，测定神经元NF-κB活性。结果与D组比较，L组血浆TNF-α浓度、电击次数和海马组织神经元NF—κB活性降低，血浆IL-10浓度升高（P〈0．05或0．01）。结论α-硫辛酸可改善糖尿病大鼠CPB后认知功能，其机制与抑制海马神经元NF—κB激活有关。

Objective To evaluate the effect of α-lipoic acid on the cognitive function after cardiopulmonary bypass （CPB） in diabetic rats. Methods Health adult male Sprague-Dawley rats, weighing 400-500 g, aged 16-22 weeks, were used in this study. Diabetes mellitus was induced by intraperitoneal streptozocin 60 mg/kg and confirmed by blood glucoses〉 16.7 mmol/L. Thirty-two diabetic rats were randomly divided into 2 groups （ n = 16 each） ： diabetes mellitus group （group D） and α-lipoi cacid group （group L） . In group L, α-lipoic acid 30 mg/kg was intraperitoneally injected once a day for 7 consecutive days starting from 6th week after induction of diabetes mellitus. While the equal volume of normal saline was given instead in group D. The two groups underwent CPB after the last administration. Before induction of diabetes mellitus, on 5th week after induction of diabetes mellitus, before CPB, at the end of CPB, and on 3 and 5 days after termination of CPB, 10 rats were chosen from each group and venous blood samples were collected for determination of plasma TNF-α and IL-10 concentrations. Ten rats in each group were chosen for detection of cognitive function before induction of diabetes mellitus, before CPB and 5 days after termination of CPB. The rats were then sacrificed and hippocampi were isolated for measurement of NF-κB activity. Results Compare with group D, the plasma TNF-α concentration, times of electric shock and activity of NF-κB in hippocampal tissues were significantly decreased and the plasma IL-10 concentration was increased in group L （ P 〈 0.05 or 0.01 ）. Conclusion α-lipoic acid can improve the cognitive function after CPB in diabetic rats and inhibition of activation of NF-κB in hippocampal neurons is involved in the mechanism.