【摘要】 该文旨在探讨复方清肝汤对四氯化碳诱导的犬急性肝损伤的治疗作用及其机制。实验选用18只12-15月龄的中华田园犬，随机分为3组，每组6只，即对照组、模型组和中药治疗组；通过腹腔注射1 mL/kg体重的四氯化碳构建急性肝损伤模型，治疗组每天灌服1 mL/kg的复方清肝汤，连续14 d。试验结束时，采血进行肝功能检测和取出肝组织样品。H&E染色观察肝组织病理学变化，qRT-PCR检测肝细胞焦亡相关基因NLRP3、ASC、GSDMD、Caspase-1、IL-1β和IL-18的mRNA表达水平，Western Blot检测肝细胞焦亡相关蛋白NLRP3、GSDMD、Caspase-1、IL-1β和IL-18的表达水平，免疫组织化学法检测细胞焦亡执行蛋白GSDMD的定位及其表达。实验结果表明，模型组AST、ALT和γ-GT的活性显著升高（P<0.05）；肝细胞排列紊乱，并出现肝细胞坏死和炎性细胞浸润；细胞焦亡相关基因NLRP3、ASC、IL-1β和IL-18表达显著升高（P<0.05），细胞焦亡相关蛋白NLRP3、GSDMD、Caspase-1、IL-1β和IL-18的表达上调；用复方清肝汤治疗后，AST、ALT和γ-GT的活性显著降低（P<0.05），肝组织病理损伤明显改善；细胞焦亡相关基因NLRP3、ASC、IL-18的mRNA表达水平显著下降（P<0.05），细胞焦亡相关蛋白NLRP3、GSDMD、Caspase-1、IL-1β和IL-18表达出现降低。复方清肝汤可通过抑制肝细胞焦亡减轻四氯化碳诱导的犬急性肝损伤。更多还原

【Abstract】 (Objective) The purpose of this study was to explore the therapeutic effect and mechanism of Compound Qinggan Decoction on acute liver injury induced by carbon tetrachloride in canines.(Methods)Eighteen mongrel canines aged from 12 to 15 months were randomly divided into three groups,with 6 canines in each group,namely the control group,the model group and the Chinese medicine treatment group. Acute liver injury model was established by intraperitoneal injection of 1 mg/kg of carbon tetrachloride,and the treatment group was given 1 ml/kg of Compound Qinggan Decoction every day for 14 days. At the end of the experiment,blood samples were collected for liver function test and liver tissue samples were taken out. H&E staining was used to observe the pathological changes of liver tissue,q RT-PCR was used to detect the mRNA expression levels of hepatocyte pyroptosis-related genes NLRP3,ASC,GSDMD,Caspase-1,IL-1β and IL-18,Western Blot was used to detect the expression levels of hepatocyte pyroptosis-related proteins NLRP3,GSDMD,Caspase-1,IL-1β and IL-18,and immunohistochemical method was used to detect the localization and expression of pyroptosis executive protein GSDMD.(Results)The experimental results showed that the activities of AST,ALT and γ-GT in the model group increased significantly(P<0.05);the arrangement of hepatocytes is disordered,and hepatocyte necrosis and inflammatory cell infiltration occur;the expression of pyroptosis-related genes NLRP3,ASC,IL-1β and IL-18 increased significantly(P<0.05),and the expression of pyroptosis-related proteins NLRP3,GSDMD,Caspase-1,IL-1β and IL-18 increased. After treatment with Compound Qinggan Decoction,the activities of AST,ALT and γ-GT decreased clearly(P<0.05),and the pathological damage of liver tissue improved obviously. The mRNA expression levels of pyroptosis-related genes NLRP3,ASC and IL-18 decreased evidently(P<0.05),and the expression levels of pyroptosis-related proteins NLRP3,GSDMD,Caspase-1,IL-1β and IL-18 decreased.(Conclusion)Compound Qinggan Decoction can alleviate acute liver injury induced by carbon tetrachloride in canines by inhibiting the pyroptosis of hepatocytes.更多还原