米诺环素预处理对老龄大鼠七氟醚麻醉致认知功能障碍及海马神经元凋亡的影响  

Minocycline pretreatment improves cognitive dysfunction and hippocampal neuronal apoptosis induced by sevoflurane anesthesia in elderly rats

作　　者：秦智刚 徐尤年 李锟[3] Qin Zhigang;Xu Younian;Li Kun(Department of Anesthesiology,Taikang Tongji Hospital(Wuhan),Wuhan 430014,Hubei Province,China)

机构地区：[1]泰康同济(武汉)医院麻醉科,430014 [2]华中科技大学同济医学院附属武汉协和医院麻醉科 [3]武汉大学中南医院普外科

出　　处：《中华老年心脑血管病杂志》2022年第8期797-801,共5页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：湖北省自然科学基金(2020CFB797)。

摘　　要：目的探讨米诺环素预处理对老龄大鼠七氟醚麻醉致认知功能障碍和海马神经元凋亡的影响。方法选取雄性SD大鼠90只,随机数表法分为对照组、七氟醚组和米诺环素组,每组30只。使用Morris水迷宫实验、旷场实验检测大鼠认知功能,ELISA检测海马组织氧化应激因子丙二醛、超氧化物岐化酶(SOD)、白细胞介素(IL)-1β、TNF-α和IL-6水平,苏木精-伊红染色和尼氏小体染色观察海马神经元细胞损伤情况,TUNEL染色观察海马神经元细胞凋亡情况,使用Western blot检测海马组织半胱氨酸天冬氨酸蛋白酶(Caspase)-9、Caspase-3、B淋巴细胞瘤2基因(Bcl-2)/Bax、谷氨酸转运体1(GLT-1)、脑源性神经营养因子(BDNF)和Toll样受体4(TLR4)、NF-κB表达。结果七氟醚组第2、3、4、5天逃避潜伏期和中央格停留时间明显高于对照组,海马组织丙二醛、IL-1β、IL-6、TNF-α、凋亡指数、Caspase-9、Caspase-3、Bcl-2/Bax、TLR4、NF-κB表达明显高于对照组,穿越原平台次数、穿梭次数和运动总距离明显低于对照组,海马组织SOD、GLT-1、BDNF表达明显低于对照组(P<0.05)。米诺环素组第2、3、4、5天逃避潜伏期和中央格停留时间明显低于七氟醚组,海马组织丙二醛、IL-1β、IL-6和TNF-α、凋亡指数、Caspase-9、Caspase-3、Bcl-2/Bax、TLR4、NF-κB表达明显低于七氟醚组,穿越原平台次数、穿梭次数和运动总距离明显高于七氟醚组;米诺环素组海马组织SOD、GLT-1、BDNF表达明显高于七氟醚组[(45.14±4.03)U/ml vs(32.61±4.36)U/ml,0.49±0.05 vs 0.16±0.03,0.27±0.03 vs 0.09±0.02,P<0.05]。结论米诺环素预处理可改善老年大鼠七氟醚所致认知功能障碍和降低海马神经元细胞凋亡率,可能与调节TLR4/NF-κB信号通路有关。Objective To determine the effects of minocycline pretreatment on cognitive dysfunction and apoptosis of hippocampal neurons induced by sevoflurane anesthesia in elderly rats.Methods Ninety male SD rats were randomly divided into the control group,sevoflurane group and minocycline group,with 30 animals in each group.The cognitive function was detected by Morris water maze test and open field test.The contents of MDA,SOD,IL-1β,TNF-αand IL-6 in the hippocampus were detected by ELISA.The damage of hippocampal neurons was observed by hematoxylin-eosin staining and Nissl body staining.The apoptosis of hippocampal neurons was observed by TUNEL staining.The expression of Caspase-9,Caspase-3,Bcl-2/Bax,GLT-1,BDNF,TLR4 and NF-κB in the hippocampus were detected by Western blotting.Results The escape latency and staying time in center area on the 2 nd,3 rd,4 th and 5 th days were significantly longer,and the times of crossing the platform,shuttling times and total movement distance were significantly lower in the sevoflurane group than the control group(P<0.05).The contents of MDA,IL-1β,IL-6 and TNF-α,apoptosis index,protein levels of Caspase-9,Caspase-3,Bcl-2/Bax,TLR4 and NF-κB in the hippocampus were significantly higher in the sevoflurane group than the control group(P<0.05).The expression of SOD,GLT-1 and BDNF in the hippocampus were significantly lower in the sevoflurane group than the control group(P<0.05).Minocycline treat-ment resulted in shorter escape latency and staying time in the center area on the 2 nd,3 rd,4 th and 5 th days,higher times of crossing the platform and shuttling times,and longer total move-ment distance,lower contens of MDA,IL-1β,IL-6 and TNF-α,apoptosis index,reduced protein levels of Caspase-9,Caspase-3,Bcl-2/Bax,TLR4 and NF-κB,and enhanced levels of SOD,GLT-1 and BDNF in the hippocampus(45.14±4.03 U/ml vs 32.61±4.36 U/ml,0.49±0.05 vs 0.16±0.03,0.27±0.03 vs 0.09±0.02,P<0.05)when compared with the sevoflurane group.Conclu-sion Minocycline pretreatment can improve cognitive dysfun

关 键 词：米诺环素 认知功能障碍 海马 神经元 麻醉 吸入 

分 类 号：R614[医药卫生—麻醉学]