TREM2在慢性脑低灌注大鼠海马区炎症反应与认知功能损害中的作用

Role of TREM2 on inflammation in hippocampus and cognitive impairment of rats with chronic cerebral hypoperfusion

目的:观察髓样细胞触发受体2(TREM2)在慢性脑低灌注大鼠海马中的表达及其在炎症反应和认知功能的作用。方法:65只SD大鼠随机分为4组,假手术组(Sham)、慢性脑低灌注组(2VO)、过表达腺相关病毒干预组(2VO+AAV-TREM2)、腺相关病毒阴性对照干预组(2VO+AAV-control)。采用Morris水迷宫评估大鼠的认知功能;Western Blot检测大鼠海马的TREM2、精氨酸酶-1(Arg-1)、诱导型一氧化氮合酶(iNOS)的蛋白表达。结果:2VO组大鼠的逃避潜伏期延长(P<0.001),目标象限游泳时间减少(P<0.05);2VO+AAV-TREM2组处理可以缩短大鼠的逃避潜伏期(P<0.05),增加其目标象限游泳时间(P<0.01)。2VO组iNOS的表达较Sham组升高(P<0.001);2VO+AAV-TREM2组iNOS的表达较2VO+AAV-control组减少(P<0.01),TREM2表达显著上升(P<0.0001),Arg-1表达升高(P<0.01)。结论:过表达TREM2可改善慢性脑低灌注大鼠的空间学习记忆功能,其机制可能与调节炎症反应有关。

Objective:To observe the expression of triggering receptor expressed on myeloid cells 2(TREM2)in hippocampus of rats with chronic cerebral hypoperfusion,and to explore its effect on inflammation and cognitive function.Methods:Sixty-five rats were randomly divided into four groups:sham-operated(Sham)group,bilateral common carotid artery ligation(2 VO)group,overexpressed adeno-associated virus treatment(2 VO+AAV-TREM2)group,and negative control adeno-associated virus treatment(2 VO+AAV-control)group.Cognitive function was assessed by Morris water maze test.The protein expression of TREM2,Arginase-1(Arg-1)and inducible nitric oxide synthase(iNOS)were detected by Western Blot analysis.Results:The escape latency of rats in 2 VO group was extended(P<0.001)and the target quadrant swimming time of 2 VO rats was declined(P<0.05),while injecting overexpressed adeno-associated virus could shorten the escape latency(P<0.05)and increase the target quadrant swimming time(P<0.01).There was higher iNOS expression in 2 VO group than that in Sham group(P<0.001).Compared with the 2 VO+AAV-control group,the expression of iNOS in 2 VO+AAV-TREM2 decreased(P<0.01)and the expression of TREM2 and Arg-1 in 2 VO+AAV-TREM2 increased(P<0.0001,P<0.01).Conclusion:The overexpressing TREM2 can improve the cognitive function of rats with chronic cerebral hypoperfusion and its mechanism may be involved in regulating inflammatory response.