苏拉明改善对乙酰氨基酚诱导小鼠急性肝损伤的作用及机制研究  

Effects of suramin on acetaminophen-induced acute liver injury in mice and the mechanism

作　　者：陈旭 刘慧茹 王婷[3] 向慎思 詹轶群 杨晓明 任广明[1] CHEN Xu;LIU Huiru;WANG Ting;XIANG Shensi;ZHAN Yiqun;YANG Xiaoming;REN Guangming(Academy of Military Medical Sciences,Academy of Military Sciences,Beijing 100850,China;Anhui Medical University,Hefei 230032,China;Beijing University of Technology,Beijing 100124,China)

机构地区：[1]军事科学院军事医学研究院,北京100850 [2]安徽医科大学,合肥230032 [3]北京工业大学,北京100124

出　　处：《军事医学》2024年第8期608-613,共6页Military Medical Sciences

基　　金：北京市自然科学基金项目(7222122)。

摘　　要：目的 探究苏拉明(Sur)在对乙酰氨基酚(APAP)诱导小鼠急性肝损伤模型中的作用及机制。方法 将8~10周龄C57BL/6J小鼠随机分为APAP组和APAP+Sur组(提前1 h注射20 mg/kg Sur),饥饿18 h后腹腔注射400 mg/kg APAP建立小鼠急性肝衰竭模型并统计存活情况;小鼠急性肝损伤模型为腹腔注射300 mg/kg APAP(其他条件不变),并增加Control组,分别在APAP处理后0、2、12 h收取肝脏组织和血清。ELISA法和CBA技术检测血清中丙氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST)的释放和炎症因子的分泌;HE染色和免疫组化检测肝组织坏死和炎性细胞浸润;DCFA-DH法和ELISA法检测肝组织活性氧(ROS)、丙二醛(MDA)以及谷胱甘肽(GSH)水平;免疫印迹法检测肝组织中JNK信号通路的活化。结果 苏拉明处理可提高APAP诱导小鼠存活率,降低血清中转氨酶和炎性因子释放,减轻APAP诱导的肝细胞坏死和肝内炎性细胞浸润。机制研究发现,苏拉明处理可延缓APAP诱导的肝内GSH耗竭,降低MDA和ROS水平,并抑制JNK通路活化。结论 该研究证实了苏拉明在对乙酰氨基酚诱导小鼠急性肝损伤中的保护作用,其机制可能与氧化应激、炎症相关。Objective To investigate the role and mechanism of suramin(Sur)in acetaminophen(APAP)-induced acute liver injury in mice.Methods 8-10 weeks old C57BL/6J mice were randomly divided into the APAP group and APAP+Sur group(20 mg/kg suramin was injected 1 h before).After 18 hrs of fasting,400 mg/kg APAP was injected intraperitoneally to establish a mouse model of acute liver failure and the survival rate was recorded.An acute liver injury model of mice was established via intraperitoneal injection of 300 mg/kg APAP(other conditions remained unchanged).A control group was also established,with liver tissues and serum collected at 0,2,and 12 hours post-APAP treatment.ELISA and CBA techniques were adopted to detect the release of alanine aminotransferase(ALT) and aspartate aminotransferase(AST)in serum and the secretion of inflammatory factors.H&E staining and immunohistochemistry were used to detect liver tissue necrosis and inflammatory cell infiltration.DCFA-DH and ELISA techniques were used to detect the levels of reactive oxygen species(ROS),malondialdehyde(MDA)and glutathione(GSH)in liver tissues.Western blotting was employed to assess the activation of the JNK signaling pathway in liver tissues.Results Suramin treatment improved the survival rate of APAP-induced mice,reduced the release of transaminases and inflammatory factors in serum,and alleviated APAP-induced liver cell necrosis and inflammatory cell infiltration in the liver.Suramin treatment delayed APAP-induced GSH depletion in the liver,reduced MDA and ROS levels,and inhibited JNK pathway activation.Conclusion This study has confirmed the protective effect of suramin against acetaminophen-induced acute liver injury in mice.The mechanism is potentially related to oxidative stress and inflammation.

关 键 词：对乙酰氨基酚 药物性肝损伤 苏拉明 氧化应激 JNK信号通路 

分 类 号：R657.3[医药卫生—外科学]