抑制炎症小体活化产物caspase-1对大鼠急性肝衰竭的保护作用  

Protective effect of inhibiting inflammasome activation product caspase-1 on acute liver failure in rats

作　　者：仵永枫 张玉林 画伟 郭彩萍 WU Yongfeng;ZHANG Yulin;HUA Wei;GUO Caiping(Department of Infection Center,Beijing Youan Hospital,Capital Medical University,Beijing 100069,China)

机构地区：[1]首都医科大学附属北京佑安医院感染中心,北京100069

出　　处：《中国医药导报》2020年第22期8-10,16,共4页China Medical Herald

基　　金：国家自然科学基金资助项目(81873761、81571178、81371399)。

摘　　要：目的探讨抑制半胱氨酸天冬氨酸特异性蛋白酶(caspase)-1对大鼠急性肝衰竭(ALF)的保护作用。方法将60只健康雄性Wistar大鼠体重150~180 g,采用随机数字表法将其分为对照组、模型组和干预组,每组20只。对照组取血清和肝组织;模型组采用大鼠腹腔联合注射1200 mg/kg D-氨基半乳糖(D-GalN)及100μg/kg脂多糖(LPS)建立ALF模型,并且分别于造模24 h后取血清及肝组织;干预组造模前2 h予大鼠尾静脉注射6 mg/kg caspase-1特异性抑制剂氟甲基酮,造模时同模型组剂量予D-GalN及LPS,造模24 h后取肝组织及血清。肝脏组织进行HE染色观察,并对血清中丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、总胆红素(TBil)和白细胞介素(IL)-1β进行检测。结果HE染色结果提示模型成功。模型组ALT、AST、TBil和IL-1β水平均高于对照组,差异均有高度统计学意义(均P<0.01),干预组大鼠ALT、AST、TBil及IL-1β水平均低于模型组,差异均有高度统计学意义(均P<0.01)。结论caspase-1所导致的炎症反应是ALF损伤的重要原因之一,有望成为ALF的预测因子和未来的治疗靶点。Objective To investigate the protective effect of inhibiting cysteinyl aspartate-specific proteinase(caspase)-1 on acute liver failure(ALF)in rats.Methods A total of 60 healthy male Wistar rats,weighing about 150-180 g,were divided into the control group,the model group and the intervention group by random number table method,with 20 rats in each group.In the control group,serum and liver tissue were collected.In the model group,rats were intraperitoneally injected with 1200 mg/kg D-galactosamine(D-Galn)and 100 g/kg liponolysaccharide(LPS)to construct the ALF model.Serum and liver tissue were collected 24 h after modeling.In the intervention group,rats were injected with 6 mg/kg of thespecific inhibitor of caspase-1,fluoromethylketone by tail vein in the two hours before modeling.The D-GalN and LPS were given to the same dose as the model group during modeling.Serum and liver tissue were collected in the 24 hours after modeling.The liver tissues were observed by HE staining,and serum levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBil)and interleukin(IL)-1βwere measured.Results HE staining results indicated that the model was successful.ALT,AST,TBil and IL-1βlevels in the model group were higher than those in the control group,the differences were all highly statistically significant(all P<0.01),and ALT,AST,TBil and IL-1βlevels in the intervention group were lower than those in the model group,the differences were all highly statistically significant(all P<0.01).Conclusion The inflammatory response caused by caspase-1 is one of the important causes of ALF injury and is expected to be a predictor of ALF and a future therapeutic target.

关 键 词：急性肝衰竭 炎症小体 氟甲基酮 半胱氨酸天冬氨酸特异性蛋白酶1 

分 类 号：R575.3[医药卫生—消化系统]