阿托伐他汀对老年脑梗死病人TLR4信号通路及认知功能的影响

Effect of atorvastatin on TLR4 signaling pathway and cognitive function in elderly patients with cerebral infarction

目的:探讨老年脑梗死合并认知功能障碍病人Toll样受体4(TLR4)信号通路的变化,以及阿托伐他汀在调节该通路中的作用及对认知功能的影响。方法:选择老年脑梗死合并认知功能障碍病人98例,随机分为观察组和对照组,各49例。对照组在常规治疗基础上,应用阿司匹林肠溶片治疗,观察组在常规治疗基础上采用阿司匹林肠溶片联合阿托伐他汀治疗,分别于治疗前及治疗后6个月比较2组病人认知功能状况、血清氧化型低密度脂蛋白(ox-LDL)、转化生长因子-β1(TGF-β1)、超敏C反应蛋白(hs-CRP)、总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C)、TLR4和核转录因子(NF)-κB、肿瘤坏死因子(TNF)-α和白细胞介素(IL)-6的表达情况以及不良反应发生情况。结果:治疗后,2组TC、TG、LDL-C、HDL-C、ox-LDL、hs-CRP、TGF-β1、TLR4、NF-κB、TNF-α和IL-6与治疗前比较差异均有统计学意义(P<0.05~P<0.01);且观察组TC、TG、LDL-C、ox-LDL、hs-CRP、TLR4、NF-κB、TNF-α和IL-6低于对照组,HDL-C、TGF-β1高于对照组(P<0.01)。治疗后,2组MMSE、MoCA评分均较治疗前提高,且观察组高于对照组(P<0.01)。2组病人不良反应:肝肾功能异常、头晕头痛、皮疹、肌痛、胃肠道反应的发生率比较差异均无统计学意义(P>0.05)。结论:TLR4信号通路参与了老年脑梗死合并认知功能障碍的发生过程,阿托伐他汀治疗可通过调节TLR4信号通路对其发挥脑保护作用。

Objective:To investigate the changes of Toll-like receptor 4(TLR4)signaling pathway in elderly patients with cerebral infarction complicated with cognitive dysfunction,and the role of atorvastatin in regulating this pathway and its influence on cognitive function.Methods:A total of 98 elderly patients with cerebral infarction and cognitive dysfunction were randomly divided into the observation group and control group(49 cases in each group).The control group was treated with aspirin enteric-coated tablets on the basis of routine treatment,while the observation group was treated with aspirin enteric-coated tablets combined with atorvastatin on the basis of routine treatment.The cognitive function,serum oxidized low-density lipoprotein(ox-LDL),transforming growth factor-β1(TGF-β1),high-sensitivity C reactive protein(hs-CRP),total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C),TLR4 and nuclear transcription factor(NF)-κB,tumor necrosis factor(TNF)-αand interleukin(IL)-6 and the occurrence of adverse reactions in the two groups were compared before and six months after treatment.Results:After treatment,there were statistically significant differences in the levels of TC,TG,LDL-C,HDL-C,ox-LDL,hs-CRP,TGF-β1,TLR4,NF-κB,TNF-αand IL-6 between the two groups compared with before treatment(P<0.05 to P<0.01);the levels of TC,TG,LDL-C,ox-LDL,hs-CRP,TLR4,NF-κB,TNF-αand IL-6 in the observation group were lower than those in the control group,and the levels of HDL-C,TGF-β1 were higher than those in the control group(P<0.01).After treatment,the MMSE and MoCA scores in the two groups were improved compared with those before treatment,and which in the observation group was higher than that in the control group(P<0.01).There were no significant differences in the incidence of adverse reactions such as abnormal liver and kidney function,dizziness and headache,rash,myalgia and gastrointestinal reactions between two groups(P>0.05).Conclusions:The TLR4 signaling pathway is involved in the occurrence of cerebral infarction combined with cognitive dysfunction in elderly,and atorvastatin can exhibit the cerebral protective role in regulating TLR4 signaling pathway.