控制性阈值低血压对老年大鼠Tau和Aβ表达及术后认知影响

Effect of controlled low threshold blood pressure on the expression of Aβ42 and p-Tau-181 protein in cerebrospinal fluid and cognition after operation in aged rats

目的探讨不同持续时间控制性阈值低血压对大鼠p-Tau-181和Aβ-42蛋白表达和认知的影响。方法健康清洁老年雄性SD大鼠39只,采用随机数字表法分为4组:C组为对照组(n=9);A1、A2、A3组(n=10)分别每日降压持续2、4、6 h,连续5 d,降压组维持平均动脉压(MAP)在50~55 mm Hg安全范围内。Morries水迷宫法检测大鼠的空间学习记忆能力,ELISA法检测脑脊液Aβ42蛋白和p-Tau-181蛋白水平。结果各组大鼠死亡情况无明显差异(P>0.05);与C组比较,A2组和A3组逃避潜伏期延长和游泳距离增加(P<0.05);术后3~7 d,大鼠脑脊液的p-Tau-181和Aβ42蛋白表达增加;随着控制性阈值低血压时间延长,与A1组相比,术后A2组和A3组逃避潜伏期延长和游泳距离增加(P<0.05);A2组和A3组的脑脊液Aβ42和p-Tau-181显著增加(P<0.05);与A2组比较,A3组Aβ42增加不明显,而p-Tau-181在术后第5天增加(P<0.05)。结论长时间的控制性阈值低血压可引起术后认知功能障碍,可能与Aβ42和p-Tau-181蛋白表达的增加相关。

Objective To investigate the effects of different duration hypotension thresholds on p-Tau-181and Aβ-42 protein expression and cognition in rats.Methods Thirty-nine healthy male SD rats were randomly divided into 4 groups:the control group(group C,n=9),the hypotension group(group A1、A2、A3,n=10).The blood pressure of group A1、A2、A3 was measured in different time of 2 h、4 h、6 h,for 5 days.The antihypertensive group of mean arterial pressure(MAP)were maintained in the 50~55 mm Hg safe range.Morris water maze was used to detect the spatial learning and memory ability of rats.The levels of Aβ42 and p-Tau-181 were detected by ELISA.Results There was no significant difference in mortality of rats in each group(P>0.05).Compared with the group C,the escape latency and swimming distance of A2 group and A3 group were increased(P<0.05).In 3~7 days after operation,the cerebrospinal fluid P-Tau-181 and Aβ42 protein expression increased in the A2group and A3 group compared with the A1 group(P<0.05).The escape latency and swimming distance of the A2group and the A3 group were significantly longer than those in the control group.Aβ42 and p-Tau-181 were significantly increased in A3 group(P<0.05).Compared with the A2 group,the increase of Aβ42 and p-Tau-181 in the A3 group was not significant(P<0.05).Conclusion Long-term controlled hypotension may lead to postoperative cognitive dysfunction which may relate to the increase of Aβ42 and p-Tau-181 protein expression.