青蒿琥酯对急性刚地弓形虫感染小鼠的治疗作用  

Therapeutic effect of artesunate on acute Toxoplasma gondii infection in mice

作　　者：钟秋婷 赵紫琪 宋健平 吕芳丽[2,3,4] Zhong Qiuting;Zhao Ziqi;Song Jianping;Lyu Fangli(Artemisinin Research Center,Guangzhou University of Chinese Medicine,Guangzhou 510405,China;Department of Clinical Laboratory,the Seventh Affiliated Hospital,Sun Yat-sen University,Shenzhen 518107,China;Department of Parasitology,Zhongshan School of Medicine,Sun Yat-sen University,Guangzhou 510080,China;Key Laboratory of Tropical Disease of Ministry of Education,Sun Yat-sen University,Guangzhou 510080,China)

机构地区：[1]广州中医药大学青蒿研究中心,广州510405 [2]中山大学附属第七医院检验科,深圳518107 [3]中山大学中山医学院寄生虫学教研室,广州510080 [4]中山大学热带病防治研究教育部重点实验室,广州510080

出　　处：《中华地方病学杂志》2022年第5期345-350,共6页Chinese Journal of Endemiology

基　　金：国家自然科学基金(81971955、81873218);广东省自然科学基金(2019A1515011667、2021A1515012115);广东省研究生教育创新计划(2021SFKC003)。

摘　　要：目的探讨青蒿琥酯对急性刚地弓形虫(简称弓形虫,Toxoplasma gondii)感染小鼠的治疗作用。方法将64只6~8周龄C57BL/6雌性小鼠(16~18 g),按体重采用随机数字表法分为4组:未感染对照组,不做处理;弓形虫感染组(Tg组),每只小鼠经腹腔注射感染100个弓形虫RH株速殖子;弓形虫感染+青蒿琥酯治疗组(Tg+ART组),每只小鼠经腹腔注射感染100个弓形虫RH株速殖子,感染3 h后经腹腔注射青蒿琥酯溶液,剂量为30 mg/kg,每天1次,共连续给药7 d;弓形虫感染+磺胺嘧啶治疗组(Tg+SDZ组),每只小鼠经腹腔注射感染100个弓形虫RH株速殖子,感染3 h后经灌胃给予磺胺嘧啶溶液,剂量为100 mg/kg,每天1次,共连续给药7 d。每组16只小鼠,其中10只小鼠用于观察生存时间,6只小鼠用于监测体重和采集组织标本。从感染后第1天起每天称量小鼠体重。在感染后第7天处死小鼠,称量每只小鼠的肝脏重量,计算肝脏指数;对肝脏组织进行石蜡包埋、切片和苏木素-伊红(HE)染色,光镜下观察各组小鼠肝脏组织的病理变化;采用实时荧光定量PCR方法检测各组小鼠肝脏组织中弓形虫主要表面抗原1(SAG1)mRNA的表达水平,以评估弓形虫虫荷。结果未感染对照组小鼠全部存活,Tg组生存时间为7~9 d,Tg+ART组为8~11 d,Tg+SDZ组为9~13 d。与Tg组相比,Tg+ART、Tg+SDZ组小鼠的生存时间均较长(P均<0.05)。在感染后第7天,与未感染对照、Tg+ART、Tg+SDZ组相比,Tg组小鼠体重较低(P均<0.05);但Tg+ART、Tg+SDZ组小鼠体重与未感染对照组相比,差异均无统计学意义(P均>0.05)。与Tg组相比,Tg+ART、Tg+SDZ组小鼠肝脏指数、肝脏组织SAG1 mRNA表达水平均较低(P<0.05或<0.001),肝脏组织病理变化也均较轻。与Tg+SDZ组相比,Tg+ART组的肝脏指数、肝脏组织SAG1 mRNA表达水平差异均无统计学意义(P均>0.05)。结论青蒿琥酯溶液经腹腔注射给药可在一定程度上延长急性弓形虫感染小鼠的生存时间,降低Objective To investigate the therapeutic effect of artesunate on mice with acute Toxoplasma gondii(T.gondii)infection.Methods Based on body weight(16-18 g),sixty-four C57BL/6 female mice aged 6-8 weeks were divided into 4 groups by random number table method:uninfected control group without treatment;T.gondii-infected group(Tg group),each mouse was intraperitoneally(i.p.)infected with 100 tachyzoites of T.gondii RH strain;T.gondii-infected+artesunate treatment group(Tg+ART group),3 hours after each mouse i.p.infected with 100 tachyzoites of T.gondii RH strain,artesunate solution was i.p.injected at a dose of 30 mg/kg,once a day for a total of 7 consecutive days;T.gondii-infected+sulfadiazine treatment group(Tg+SDZ group),3 hours after each mouse i.p.infected with 100 tachyzoites of T.gondii RH strain,sulfadiazine solution was orally administrated at a dose of 100 mg/kg,once a day for a total of 7 consecutive days.There were 16 mice in each group,in which 10 mice were used to observe survival time and 6 mice were used to monitor body weight and collect tissue samples.Mice were weighed every day from day 1 post infection(p.i.);mice were sacrificed at day 7 p.i.,the liver weights of mice were weighed and the liver indexes were calculated;liver tissues were paraffin-embedded,sectioned,and stained with hematoxylin-eosin(HE),and the pathological changes of liver tissues of mice in each group were observed under a light microscope.The expression levels of T.gondii major surface antigen 1(SAG1)in the liver tissues of mice in each group were detected by real-time quantitative PCR for evaluating parasite load.Results All mice in the uninfected control group were survived.The survival time was 7-9 days in Tg group,8-11 days in Tg+ART group,and 9-13 days in Tg+SDZ group.Compared with Tg group,the survival times of mice in Tg+ART group and Tg+SDZ group were significantly longer(P<0.05).On day 7 p.i.,compared with uninfected control group,Tg+ART group or Tg+SDZ group,the body weight of mice in Tg group was lower(P<0.05);howeve

关 键 词：弓形虫属 青蒿琥酯 小鼠 肝脏 病理 

分 类 号：R285.5[医药卫生—中药学]