下调AQP-4对脑缺血再灌注损伤模型大鼠的干预效果及作用机制研究

Effect and mechanism of downregulating AQP-4 in cerebral ischemia-reperfusion injury of rats

目的探究下调AQP-4对脑缺血再灌注损伤模型大鼠的干预效果及作用机制。方法选取40只SD健康雄性大鼠,分10只为正常组,其余30只SD健康雄性大鼠分为模型组、下调AQP-4组、上调AQP-4组,对四组大鼠分别进行干预。使用Western blot法检测AQP-4、BMP4、P-Smad表达,使用散射比浊法检测TNF-α、IL-1β水平。对各组大鼠学习记忆能力、神经功能。脑组织含水量进行检测。结果与正常组比较,其他三组大鼠各时间点逃避潜伏期较长,穿越平台次数较低(P<0.05);与模型组和上调AQP-4组相比,下调AQP-4组大鼠各时间点逃避潜伏期较短、穿越平台次数高(P<0.05);与正常组相比,模型组、上调AQP-4组、下调AQP-4组神经功能评分上升,脑组织含水量增多(P<0.05);与模型组和上调AQP-4组相比,下调AQP-4组神经功能评分下降,脑组织含水量减少(P<0.05);与正常组比较,其他三组大鼠TNF-α、IL-1β水平升高(P<0.05);与模型组和上调AQP-4组相比,下调AQP-4组大鼠TNF-α、IL-1β水平下降(P<0.05);与正常组比较,其他三组大鼠AQP-4表达上升、BMP4、P-Smad表达下降(P<0.05);与模型组和上调AQP-4组相比,下调AQP-4组大鼠AQP-4表达下降、BMP4、P-Smad表达上升(P<0.05);与正常组比较,其他三组大鼠Na^(+)、P-dp含量上升(P<0.05);与模型组和上调AQP-4组相比,下调AQP-4组大鼠Na^(+)、P-dp含量下降(P<0.05)。结论下调AQP-4能够通过BMP4/Smad通路对脑缺血再灌注损伤模型大鼠进行干预,修复脑内血脑屏障,改善大鼠学习记忆能力,降低大鼠的炎症反应。

Objective To explore the therapeutic effect and mechanism of downregulating AQP-4 in cerebral ischemia-reperfusion injury model rats.Methods A total of 10 healthy male SD rats were used as the normal group and 30 rats were divided into model,downregulated AQP-4,and upregulated AQP-4 groups.AQP-4,BMP4,and P-Smad expression was examined by Western blot,TNF-αwas detected by resonance light-scattering turbidimetry,and IL-1βlevels were measured.Learning and memory abilities as well as neurological functions were evaluated in each group of rats.Water content was measured in brain tissue.Results Compared with the normal group,rats in the other three groups had a longer escape latency and lower number of crossings of the platform at each time point(P<0.05).Compared with model and upregulated AQP-4 groups,the downregulated AQP-4 group had a shorter escape latency and higher number of platform crossings at each time point(P<0.05).Compared with the normal group,neurological scores of model,upregulated AQP-4,and downregulated AQP-4 groups were increased,while water content in brain tissue was increased(P<0.05).Compared with model and upregulated AQP-4 groups,the downregulated AQP-4 group showed decreases in neurological scores and brain water content(P<0.05).Compared with the normal group,the other three groups of rats had increased TNF-αand IL-1βlevels(P<0.05)Compared with model and upregulated AQP-4 groups,TNF-αand IL-1βlevels were decreased in the downregulated AQP-4 group(P<0.05).Compared with the normal group,the other three groups showed an increase in expression of AQP-4 and decreased expression of BMP4 and P-Smad(P<0.05).Compared with model and upregulated AQP-4 groups,the downregulated AQP-4 group showed a decrease in expression of AQP-4 and increased expression of BMP4 and P-Smad(P<0.05).Compared with the normal group,Na^(+)and P-dp were increased in the other three groups(P<0.05).Compared with model and upregulated AQP-4 groups,the contents of Na^(+)and P-dp were decreased in the downregulated AQP-4 group(P<0.05).Conclusions Downregulation of AQP-4 rescues the blood-brain barrier,improves learning and memory abilities,and reducea the inflammatory response in cerebral ischemia-reperfusion injury model rats through the BMP4/Smad pathway.