川芎嗪对脓毒症相关性脑病大鼠海马炎症反应的影响  

Effect of tetramethylpyrazine on hippocampal inflammatory responses in rats with sepsis-associated encephalopathy

作　　者：朱浩[1] 张益维[1] 周海东[1] 陈勇杰[1] 卢子会[1] 陈益君[1] 黄长顺[1] Zhu Hao;Zhang Yiwei;Zhou Haidong;Chen Yongjie;Lu Zihui;Chen Yijun;Huang Changshun(Department of Anesthesiology,Ningbo First Hospital,Ningbo 315010,China)

机构地区：[1]宁波市第一医院麻醉科,315010

出　　处：《中华麻醉学杂志》2020年第5期629-632,共4页Chinese Journal of Anesthesiology

基　　金：浙江省医药卫生科技计划项目(2017KY577,2019RC260,2019KY159);宁波市自然科学基金项目(2016A610155)。

摘　　要：目的评价川芎嗪对脓毒症相关性脑病大鼠海马炎症反应的影响。方法健康雄性SD大鼠60只,12~14周,体重240~270 g,采用随机数字表法分为4组(n=15):假手术组(Sham组)、脓毒症相关性脑病组(SAE组)、低剂量川芎嗪组(L-TMP组)和高剂量川芎嗪组(H-TMP组)。采用盲肠结扎穿孔(CLP)法制备脓毒症相关性脑病模型。模型制备前5 d,L-TMP组和H-TMP组分别腹腔注射川芎嗪5或20 mg/kg,1次/d。于CLP后1~5 d行Morris水迷宫实验测试认知功能,记录逃避潜伏期和靶象限活动时间比率。于CLP后1 d,处死5只大鼠,取海马组织,采用ELISA法测定海马IL-1β、TNF-α和IL-6含量。于水迷宫测试结束后,处死大鼠,取海马组织,采用Western blot法测定Toll样受体1(TLR1)、活化caspase-3、Bax和Bcl-2的表达。结果与Sham组比较,SAE组、L-TMP组和H-TMP组逃避潜伏期延长,靶象限活动时间比率降低,TLR1、活化caspase-3和Bax表达上调,Bcl-2表达下调,SAE组和L-TMP组海马IL-1β、TNF-α、IL-6含量升高(P<0.05);与SAE组比较,L-TMP组和H-TMP组逃避潜伏期缩短,靶象限活动时间比率升高,海马IL-1β、TNF-α、IL-6含量降低,TLR1、活化caspase-3和Bax下调,Bcl-2表达上调(P<0.05)。结论川芎嗪减轻大鼠脓毒症相关性脑病的机制可能与抑制海马炎症反应有关。Objective To evaluate the effect of tetramethylpyrazine on hippocampal inflammatory responses in rats with sepsis-associated encephalopathy.Methods Sixty healthy male Sprague-Dawley rats,aged 12-14 weeks,weighing 240-270 g,were divided into 4 groups(n=15 each)using a random number table method:sham operation group(group Sham),sepsis-associated encephalopathy group(group SAE),low-dose tetramethylpyrazine group(group L-TMP),and high-dose tetramethylpyrazine group(group H-TMP).Sepsis-associated encephalopathy was induced by cecal ligation and puncture(CLP)in anesthetized rats.Tetramethylpyrazine 5 and 20 mg/kg were intraperitoneally injected once a day in L-TMP and H-TMP groups,respectively,at 5 days prior to CLP.Morris water maze test was performed at 1-5 days after CLP to assess the cognitive function,and the escape latency and ratio of time spent in the target quadrant were recorded.Five rats were sacrificed at 1 day after CLP,the brains were removed,and the hippocampi were isolated for determination of the contents of interleukin-1beta(IL-1β),tumor necrosis factor-alpha(TNF-α)and IL-6 by enzyme-linked immunosorbent assay.Rats were sacrificed after the end of Morris water maze test,and hippocampi were removed for detection of the expression of Toll-like receptor 1(TLR1),activated caspase-3,Bax and Bcl-2 by using Western blot.Results Compared with group Sham,the escape latency was significantly prolonged,the ratios of time spent in the target quadrant were decreased,the expression of TLR1,activated caspase-3 and Bax was up-regulated,and the expression of Bcl-2 was down-regulated in group SAE,group L-TMP and group H-TMP,and the contents of IL-1β,TNF-αand IL-6 were significantly increased in group SAE and group L-TMP(P<0.05).Compared with group SAE,the escape latency was significantly shortened,the ratio of time spent in the target quadrant was increased,the contents of IL-1β,TNF-αand IL-6 were decreased,the expression of TLR1,activated caspase-3 and Bax was down-regulated,and the expression of Bcl-2 was up-re

关 键 词：川芎嗪 脓毒症 脑疾病 炎症 海马 

分 类 号：R285.5[医药卫生—中药学]