替格瑞洛对盲肠结扎穿刺术诱导的脓毒血症小鼠免疫调节机制研究  

Study on the immune regulation mechanism of ticagrelor on cecal ligation and puncture-induced sepsis mice

作　　者：余晓婷[1] 汪建英[1] 张明 王剑荣[2] YU Xiao-ting;WANG Jian-ying;ZHANG Ming;WANG Jian-rong(Department of Critical Care Medicine,Hangzhou Cancer Hospital,Hangzhou 310000,Zhejiang Province,China;Department of Critical Care Medicine,Hangzhou First People’s Hospital,Hangzhou 310000,Zhejiang Province,China)

机构地区：[1]杭州市肿瘤医院危重症医学科,浙江杭州310000 [2]杭州市第一人民医院危重症医学科,浙江杭州310000

出　　处：《中国临床药理学杂志》2021年第16期2213-2216,2220,共5页The Chinese Journal of Clinical Pharmacology

基　　金：浙江省医药卫生科技计划基金资助项目(2018KY581)。

摘　　要：目的探讨替格瑞洛对脓毒血症小鼠免疫调节的影响及其对高迁移率蛋白1(HMGB-1)的调控作用。方法用盲肠结扎穿刺术(CLP)建立脓毒血症模型,小鼠随机分为假手术组、模型组和低、中、高剂量实验组,每组12只。低、中、高剂量实验组分别给予替格瑞洛5,10,15 mg·kg^(-1)替格瑞洛,灌胃;假手术组和模型组给予等量蒸馏水,灌胃。观察小鼠存活率及检测小鼠脾指数;用生化分析仪检测脓毒血症小鼠血清谷草转氨酶(GOT)、谷丙转氨酶(GPT)水平;用酶联免疫吸附测定法(ELISA)法检测脓毒血症小鼠血清干扰素-γ(IFN-γ)、白细胞介素-17(IL-17)、白细胞介素-4(IL-4)的水平;用蛋白质印迹(Western blot)法检测B细胞淋巴瘤/白血病-2(Bcl-2)、Bcl-2相关X蛋白(Bax)、HMGB-1蛋白表达量。结果假手术组、模型组和低、中、高剂量实验组存活率为100%,33.33%,50.00%,58.33%,75.00%;脾指数为4.61±0.83,2.39±0.16,2.88±0.18,3.56±0.30,4.24±0.35;GPT含量为(41.02±6.06),(185.50±16.68),(150.23±12.70),(106.41±11.80),(70.44±6.79)U·L^(-1);GOT含量为(50.11±6.37),(305.72±29.35),(231.69±17.28),(153.02±18.76),(90.34±10.38)U·L^(-1);IFN-γ含量为(119.64±15.70),(80.96±6.23),(89.99±14.18),(101.04±14.92),(116.78±12.58)pg·mL^(-1);IL-17含量为(10.07±1.07),(39.94±2.98),(31.11±1.46),(23.95±2.19),(15.05±1.94)pg·mL^(-1);IL-4含量为(14.19±1.16),(43.20±6.03),(33.60±4.76),(24.93±2.63),(18.91±1.69)pg·mL^(-1);HMGB-1蛋白表达量为0.20±0.03,0.89±0.08,0.69±0.06,0.41±0.07,0.22±0.05。上述指标,假手术组和模型组比较,差异均有统计学意义(均P<0.05);模型组与低、中、高剂量实验组比较,差异均有统计学意义(均P<0.05)。结论替格瑞洛可能通过下调HMGB-1的表达而调节辅助型T细胞1(Th1)/辅助型T细胞2(Th2)、辅助性T细胞17(Th17)/调节性T细胞(Treg)平衡进而保护机体免受免疫损伤。Objective To explore the effect of ticagrelor on the immune regulation of sepsis mice and its regulation of high mobility group box-1(HMGB-1).Methods Cecal ligation and puncture(CLP)was used to establish sepsis model.The mice were randomly divided into sham operation group,model group and low,medium,high dose experimental groups,12 mice in each group.The low,medium and high dose experimental groups were given 5,10,15 mg·kg^(-1) ticagrelor,sham operation group and model group were given the same amount of distilled water by gavage.The survival rate of mice were detected and the spleen index of mice were observed;biochemical analyzer was used to detect the levels of serum glutamic-oxaloacetic transaminase(GOT)and glutamic-pyruvic transaminase in septic mice(GPT);enzyme-linked immunosorbent assay(ELISA)method was used to detect the levels of serum interferon-γ(IFN-γ)and interleukin-17(IL-17),interleukin-4(IL-4);Western blot was used to detect the expression levels of B cells lymphoma/leukemia-2(Bcl-2),Bcl-2 associated X protein(Bax),HMGB-1 protein.Results The survival rate of sham operation group,model group and low,medium and high dose experimental groups were 100%,33.33%,50.00%,58.33%,75.00%;spleen index were 4.61±0.83,2.39±0.16,2.88±0.18,3.56±0.30,4.24±0.35;GPT content were(41.02±6.06),(185.50±16.68),(150.23±12.70),(106.41±11.80),(70.44±6.79)U·L^(-1);GOT content were(50.11±6.37),(305.72±29.35),(231.69±17.28),(153.02±18.76),(90.34±10.38)U·L^(-1);IFN-γcontent were(119.64±15.70),(80.96±6.23),(89.99±14.18),(101.04±14.92),(116.78±12.58)pg·mL^(-1);IL-17 content were(10.07±1.07),(39.94±2.98),(31.11±1.46),(23.95±2.19),(15.05±1.94)pg·mL^(-1);IL-4 content were(14.19±1.16),(43.20±6.03),(33.60±4.76),(24.93±2.63),(18.91±1.69)pg·mL^(-1);HMGB-1 protein expression were 0.20±0.03,0.89±0.08,0.69±0.06,0.41±0.07,0.22±0.05.For the above indicators,the difference between sham operation group and model group were statistically significant(all P<0.05).The model group was compared with low,medi

关 键 词：替格瑞洛 脓毒血症 免疫调节 炎性反应 

分 类 号：R972[医药卫生—药品]