Aβ1-42诱导的老年性痴呆大鼠血清中miR-221表达与认知功能的关系

Relationship between serum miR-221 expression and cognitive function in rats with Aβ1-42-induced Alzheimer’s disease

目的探讨老年性痴呆(AD)大鼠血清中miR-221的表达及其与认知功能的关系。方法采用Aβ1-42诱导的老年性痴呆大鼠模型,将构建的miRNA-221过表达慢病毒尾静脉注射至造模成功的AD大鼠,分别设置AD组、AD+miR-221过表达组、AD+空载体组及正常对照组。采用RT-qPCR检测各组大鼠血清中miR-221水平,水迷宫实验检测各组大鼠的认知功能,HE染色观察大脑海马区和大脑皮质神经元的病理变化,Western-blot检测大脑组织中BACE1蛋白的表达情况。结果AD组、AD+空载体组及AD+miR-221过表达组中miR-221水平均显著低于对照组(P<0.05);AD+miR-221过表达组显著高于AD组、AD+空载体组(P<0.05)。与正常对照组比较,AD组、AD+空载体组及AD+miR-221过表达组大鼠逃避潜伏期显著延长(P<0.05),即认知功能下降;AD+miR-221过表达组与AD组、AD+空载体组比较,大鼠逃避潜伏期明显缩短,认知功能提高,差异有统计学意义(P<0.05)。AD组和AD+空载体组大鼠海马区及大脑皮层区神经元受损严重;AD+过表达组神经元损伤得到显著改善,且趋向于正常对照组。与正常对照组比较,AD组和AD+空载体组大脑组织中BACEl蛋白表达量明显升高,差异有统计学意义(P<0.05);AD+过表达组低于AD组和AD+空载体组,高于正常对照组,差异均有统计学意义(P<0.05)。结论miR-221可能是通过降低BACEl的表达水平进而抑制Aβ1-42诱导的大鼠老年性痴呆,提高大鼠认知功能。

Objective To investigate the expression of miR-221 in serum of rats with Alzheimer’s disease(AD)and its relationship with cognitive function.Methods A rat model of AD induced by Aβ1-42 was established,and the miRNA-221 overexpression lentivirus was injected into AD rats after successful modeling,The rats were divided into AD group,AD+miR-221 overexpression group,AD+empty vector group and normal control group.The levels of miR-221 in the serum of each group were detected by RT qPCR,and the cognitive function of each group was detected by water maze test.The pathological changes of neurons in hippocampus and cerebral cortex were observed by HE staining,and the expression of BACE1 protein in brain tissue was detected by Western blot.Results The miR-221 levels in AD group,AD+empty vector group and AD+miR-221 overexpression group were significantly lower than those in control group(P<0.05),and the miR-221 levels in AD+miR-221 overexpression group were significantly higher than those in AD group and AD+empty vector group(P<0.05).as compared with that in normal control group,the escape latency in AD group,AD+empty vector group and AD+miR-221 overexpression group was significantly prolonged(P<0.05),indicating the cognitive function was decreased.As compared with that in AD group and the AD+empty vector group,the escape latency was significantly shortened in AD+miR-221 overexpression group,and the cognitive function was significantly improved(P<0.05).Neurons in the hippocampus and cerebral cortex of the AD group and the AD+empty vector group were severely damaged.The neuronal damage in the AD+overexpression group was significantly ameliorated and tended to be normal,as in the normal control group.Compared with the normal control group,the expression of BACE1 protein in brain tissue of AD group and AD+empty vector group was significantly increased,and the difference was statistically significant(P<0.05).In addition,the expression of BACE1 protein in AD+overexpression group was lower than that in AD group and AD+empty vector group,but higher than that in the normal control group,and the difference was statistically significant(P<0.05).Conclusion The miR-221 may reduce the expression of BACE1,thereby inhibiting Aβ1-42-induced AD in rats and improving their cognitive function.