吡喹酮对脂多糖诱导脓毒症小鼠急性肝损伤的保护作用  

Protective effect of praziquantel on acute liver injury induced by lipopolysaccharide in mice with sepsis

作　　者：戴昱婕 胡婷婷 孙捷睿 邱竞帆[1] 缪婷婷 王勇[1] DAI Yujie;HU Tingting;SUN Jierui;QIU Jingfan;MIAO Tingting;WANG Yong(Department of Pathogen Biology,Nanjing Medical University,Nanjing 21l166,China;Department of Nuclear Medicine,The Second Affiliated Hospital of Nanchang University)

机构地区：[1]南京医科大学基础医学院病原生物学系,江苏南京211166 [2]南昌大学第二附属医院核医学科

出　　处：《中国病原生物学杂志》2024年第10期1123-1128,共6页Journal of Pathogen Biology

基　　金：国家自然科学基金项目(No.82072301)。

摘　　要：目的 探讨吡喹酮(praziquantel, PZQ)对脂多糖(lipopolysaccharide, LPS)诱导脓毒症小鼠急性肝损伤的保护作用。方法 将56只6-8周龄C57BL/6雄鼠每组14只随机分成4组:正常对照组,PZQ对照组,LPS模型组(LPS组)和PZQ治疗组。以LPS(10 mg/kg)构建小鼠脓毒症模型,PZQ(300 mg/kg)灌胃治疗24 h。每组分别取8只小鼠,每12 h观察生存情况,直至PZQ治疗组小鼠全部死亡,绘制生存曲线;各组另取6只小鼠检测血清中谷草转氨酶(glutamicoxaloacetictransaminase, AST)和谷丙转氨酶(glutamic pyruvic transaminase, ALT)水平;qRT-PCR检测肝脏TNF-α、IL-1β、IL-6、NLRP3 mRNA相对表达水平。体外培养RAW264.7巨噬细胞,以1μg/ml浓度的LPS刺激RAW264.7巨噬细胞4 h后用30μg/ml PZQ处理24 h, qRT-PCR检测各组TNF-α、IL-1β、IL-6、NLRP3 mRNA相对表达水平;流式细胞术检测各组Ly-6C~(hi)亚群及Ly-6C~(lo)亚群巨噬细胞数量变化。结果 各组小鼠生存曲线显示,PZQ治疗组生存率高于LPS造模组。血清AST、ALT检测结果显示,PZQ灌胃治疗组ALT、AST水平均明显低于LPS模型组(P<0.05)。小鼠肝脏与体外RAW264.7巨噬细胞系中qRT-PCR检测结果显示,PZQ灌胃治疗组均低于LPS模型组(P<0.05),PZQ处理组均低于LPS刺激组(P<0.05)。流式细胞术检测结果显示,PZQ处理组Ly-6C^(hi)亚群巨噬细胞的百分率低于LPS刺激组(P<0.05);Ly-6C^(lo)亚群巨噬细胞的百分率高于LPS刺激组(P<0.05)。结论 PZQ通过促进Ly-6C^(hi)亚群巨噬细胞向Ly-6C^(lo)亚群巨噬细胞转化,减少促炎因子的表达,缓解脓毒症小鼠肝脏炎症反应,进而提高脓毒症小鼠生存率。Objective To investigate the protective effects of praziquantel(PZQ)on lipopolysaccharide(LPS)induced acute liver injury in sepsis mice.Methods 56 C57BL/6 male mice aged 6-8 weeks were randomly divided into 4 groups:normal control group,PZQ control group,LPS model group(LPS group)and PZQ treatment group.The mouse sepsis model was established with LPS(10 mg/kg)and treated with PZQ(300 mg/kg)for 24 h.The survival of 8 mice in each group was observed every 12 hours until all mice in the PZQ treatment group died,and the survival curve was drawn.6 mice in each group were selected to detect the glutamic oxalotransaminase(AST)and glutamic pyruvic transaminase(ALT)levels in serum.The relative expression levels of TNF-α,IL-1p,IL-6 and NLRP3 mRNA in liver were detected by qRT-PCR.RAW264.7 macrophages were cultured in vitro and stimulated with 1μg/ml LPS for 4 h and treated with 30μg/ml PZQ for 24 h.The mRNA relative expression levels of TNF-α,IL-1β,IL-6 and NLRP3 in each group were detected by qRT-PCR.The number of macrophages in Ly-6C^(lo)subgroup and Ly-6Clo subgroup were detected byflowcytometry.Results The survival curve of each group showed that the survival rate of PZQ group was higher than that of LPS group.The results of serum AST and ALT detection showed that the levels of ALT and AST in PZQ group were significantly lower than those in LPS group(P<O.05).The results of qRT-PCR in mouse liver and RAW264.7 macrophage cells in vitro showed that PZQ treatment group was lower than LPS model group(P<0.05),and PZQ treatment group was lower than LPS stimulation group(P<0.05).Flow cytometry showed that the percentage of Ly-6Ch"subgroup macrophages in PZQ treated group was lower than that in LPS stimulated group(P<0.05).The percentage of macrophages in Ly-6C^(lo) subgroup was higher than that in LPS stimulated group(P<0.05).Conclusion PZQ can promote the transformation of Ly-6Chi subgroup macrophages into Ly-6C^(lo) subgroup macrophages,reduce the expression of pro-inflammatory factors,relieve liver inflammation in seps

关 键 词：脓毒症 肝脏损伤 炎症 吡喹酮 巨噬细胞 

分 类 号：R459.7[医药卫生—急诊医学]