RSK信号通路抑制剂联合阿奇霉素在沙眼衣原体感染小鼠模型中的作用研究  

Effect of RSK signal pathway inhibitor combined with azithromycin on Chlamydia trachomatis infected mice

作　　者：董凯凯 陈丹丹 朱迎春 张晶晶 葛建彬[1] DONG Kaikai;CHEN Dandan;ZHU Yingchun;ZHANG Jingjing;GE Jianbin(Department of Pharmacy,Nantong Second People's Hospital,Nantong 226000,China)

机构地区：[1]南通市第二人民医院药剂科,江苏南通226000

出　　处：《广东药科大学学报》2022年第1期23-28,共6页Journal of Guangdong Pharmaceutical University

基　　金：南通市科技局项目(JCZ18032);江苏省青年医学重点人才培养项目(QNRC2016397);江苏省药学会天晴医院药学基金课题(Q2019157)。

摘　　要：目的探讨核糖体S6蛋白激酶(RSK)信号通路抑制剂LJI308联合阿奇霉素在沙眼衣原体(chlamydiatrachomatis,CT)感染小鼠模型中的作用。方法64只阴道接种CT感染液的Balb/c雌性小鼠以随机数字表法分为感染组、LJI308组、阿奇霉素组、LJI308联合阿奇霉素组,每组16只;未进行阴道接种CT感染液的16只Balb/c雌性小鼠设为空白对照组。感染后第4天、7天、14天、21天、28天采用直接免疫荧光法检测CT感染阳性率和衣原体数量,HE染色法观察小鼠生殖道组织病理症状,Westernblot法检测RSK信号通路相关蛋白表达。结果感染后第4天、7天、14天、21天、28天,感染组小鼠CT感染阳性率均显著高于空白对照组(P<0.05);感染后第14天,LJI308组和阿奇霉素组小鼠CT感染阳性率显著低于感染组(P<0.05);感染后第21天、28天,LJI308联合阿奇霉素组小鼠CT感染阳性率显著低于LJI308组和阿奇霉素组(P<0.05)。感染后第7天、14天、21天、28天,LJI308组和阿奇霉素组小鼠阴道分泌液中CT包涵体数目显著少于感染组(P<0.05),LJI308联合阿奇霉素组小鼠阴道分泌液中CT包涵体数目显著少于LJI308组和阿奇霉素组(P<0.05)。与空白对照组比较,感染组小鼠生殖道组织存在明显组织损伤,LJI308和阿奇霉素单独作用可改善小鼠生殖道组织病理症状,LJI308联合阿奇霉素作用对小鼠生殖道组织病理症状的改善效果较LJI308、阿奇霉素更为明显。LJI308显著降低感染小鼠生殖道组织中p-RSK/RSK比值,且LJI308联合阿奇霉素组小鼠生殖道组织中p-RSK/RSK比值显著低于LJI308组和阿奇霉素组,差异均有统计学意义(P<0.05)。结论LJI308联合阿奇霉素应用于CT感染起协同抑制作用。Objective To investigate the effect of ribosomal S6 kinase(RSK)signal pathway inhibitor LJI308 combined with azithromycin on mice infected with Chlamydia trachomatis(CT).Methods Sixty-four Balb/c female mice,inoculated with CT infection fluid were randomly divided into infection group,LJI308 group,azithromycin group,LJI308 combined with azithromycin group,with sixteen mice in each group;and sixteen Balb/c female mice without vaginal inoculation of CT infection fluid were set as blank control group.On the 4th,7th,14th,21st and 28th day after infection,the positive rate of CT infection and the number of chlamydia were detected by direct immunofluorescence,the pathological symptoms of genital tract were observed by HE staining,and the expression of RSK signaling pathway related proteins was detected by Western blot.Results On the 4th,7th,14th,21st and 28th day after infection,the positive rate of CT infection in the infected group was significantly higher than that in the blank control group(P<0.05).On the 14th day after infection,the positive rates of CT infection in mice of LJI308 group and azithromycin group were significantly lower than those of infection group(P<0.05).On the 21st and 28th day after infection,the positive rate of CT infection in LJI308 combined with azithromycin group was significantly lower than that in LJI308 and azithromycin groups(P<0.05).At the 7th,14th,21st and 28th day after infection,the number of CT inclusion bodies in vaginal secretion of mice in LJI308 group and azithromycin group were significantly lower than those in infection group(P<0.05),and the number of CT inclusion bodies in vaginal secretion of mice in LJI308 combined with azithromycin group were significantly lower than those in LJI308 group and azithromycin group(P<0.05).Compared with the blank control group,there was obvious tissue damage in the reproductive tract tissue of mice in the infection group.LJI308 and azithromycin alone could improve the pathological symptoms of mouse reproductive tract tissue.LJI308 combined wi

关 键 词：信号通路抑制剂 阿奇霉素 沙眼衣原体 生殖道 包涵体 

分 类 号：R965[医药卫生—药理学]