不同程度控制性降压对大鼠海马CA1区Aβ蛋白及tau蛋白磷酸化表达的影响

Effects of different levels of controlled hypotension on Aβ protein and tau protein phosphorylation expression in hippocampal CA1

目的 评价不同程度控制性降压对大鼠海马CA1区Aβ蛋白及tau蛋白磷酸化表达的影响。方法 选择健康成年雄性SD大鼠96只,体重280-320g,采用随机数字表法,将大鼠随机分为4组(n=24)。正常对照组(C组):不做任何处理;控制性降压Ⅰ组(CH1组):联合应用硝普钠和艾司洛尔使MAP降压基础值的30%;控制性降压Ⅱ组(CH2组):联合应用硝普钠和艾司洛尔使MAP降压基础值的45%;控制性降压Ⅲ组(CH3组):联合应用硝普钠和艾司洛尔使MAP降压基础值的60%;并维持目标血压1h,所有大鼠降压1h后均复压,复压时间为2h。术中严密监测大鼠的各项血流动力学指标,并进行动脉血气分析,分别于术前(T0)及术后1、3和7d(T1-3)时对各组大鼠进行Morris水迷宫实验测定认知功能,于水迷宫测试结束后处死大鼠,取大鼠海马组织,进行HE染色,光镜下观察大鼠海马组织CA1区神经元病理学结果 ,TUNEL法测定海马神经元凋亡情况,并采用Western blot法检测海马Aβ蛋白和磷酸化tau蛋白表达情况。结果 与C组比较,CH2及CH3组大鼠术后逃避潜伏期延长,穿越平台次数减少,海马Aβ蛋白和磷酸化tau蛋白表达升高(P<0.05),CH1组比较差异无统计学意义(P>0.05);与CH1组比较,CH2及CH3组大鼠术后逃避潜伏期延长,穿越平台次数减少,海马Aβ蛋白和磷酸化tau蛋白表达升高(P<0.05);与CH2组比较,CH3组大鼠术后逃避潜伏期延长,穿越平台次数减少,海马Aβ蛋白和磷酸化tau蛋白表达升高(P<0.05)。结论 控制性降压达一定程度后可导致大鼠术后认知功能障碍,其机制可能与其上调海马CA1区Aβ蛋白及磷酸化tau蛋白表达有关。

Objective To investigate the effect of different levels of controlled hypotension on Aβ protein and tau protein phosphorylation expression in hippocampal CA1 region. Methods Niety-six adult male SD rats,weighing 280-320 g,were randomly divided into four groups（n=24 each）：Control group（group C,without any treatment）,controlled hypotension Ⅰ group（group CH1,mean arterial pressure fell to 30% of the baseline）,controlled hypotension Ⅱ group（group CH2,mean arterial pressure fell to 45% of the baseline）,and controlled hypotension Ⅲ group（group CH3,mean arterial pressure fell to 60% of the baseline）. And the target blood pressure was maintained 1h. During the study,monitored the MAP and HR of the rats and observed the blood gas analysises. Cognitive function was assessed by Morris water maze test. The hippocampus was removed for microscopic examination,detection of neuronal apoptosis by TUNEL,and determination of the expression Aβ protein and tau protein phosphorylation in hippocampal CA1 region by Western blot. Results Compared with group C,the escape latency was significantly prolonged,and the frequency of crossing the original platform was decreased,the expression Aβ protein and tau protein phosphorylation in hippocampal CA1 region was increased in group CH2 and CH3（P〈0.05）,and there was no significant difference in group CH1（P 0.05）.Compared with group CH1,the escape latency was significantly prolonged,and the frequency of crossing the original platform was decreased,the expression Aβ protein and tau protein phosphorylation in hippocampal CA1 region was increased in group CH2 and CH3（P〉0.05）. Compared with group CH2,the escape latency was significantly prolonged,and the frequency of crossing the original platform was decreased,the expression Aβ protein and tau protein phosphorylation in hippocampal CA1 region was increased in group CH3（P〈0.05）. Conclusion Controlled hypotension can cause postoperative cognitive dysfunction in rats,and the mechanism maybe up-expression Aβ protein and tau protein phosphorylation in hippocampal CA1 region.