解毒护肝方抑制NLRP3炎症小体活化缓解对乙酰氨基酚诱导的小鼠急性肝损伤  

Jiedu Hugan Recipe Inhibiting the Activation of NLRP3 Inflammatory Bodies And Alleviating Acetaminophen-induced Acute Liver Injury in Mice

作　　者：于泽鹤 胡巍巍[2] 巨晓宁 彪雅宁 王茜 韩雪 张一昕 YU Ze-he;HU Wei-wei;JU Xiao-ning;BIAO Ya-ning;WANG Xi;HAN Xue;ZHANG Yi-xin(College of Pharmacy,Hebei University of Chinese Medicine,Shijiazhuang 050091)

机构地区：[1]河北中医学院药学院,石家庄050091 [2]石家庄医学高等专科学校,石家庄050599 [3]河北省宁晋县中西医结合医院,邢台055550

出　　处：《河北中医药学报》2022年第1期1-5,共5页Journal of Hebei Traditional Chinese Medicine and Pharmacology

基　　金：河北省中医药管理局科研计划项目:No.2020308。

摘　　要：目的:探讨解毒护肝方对对乙酰氨基酚(APAP)所致小鼠急性肝损伤(ALI)的保护作用及其机制。方法:60只C57BL/6N小鼠随机分为正常组、模型组、阳性药组以及解毒护肝方低、中、高剂量组。APAP造模同时,分别灌胃给予相应药物治疗,连续14 d。实验结束后,采集血清和肝组织,检测血清中丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、直接胆红素(DBIL)、总胆红素(TBIL)、白介素-1β(IL-1β)和白介素-18(IL-18)的活性或含量;苏木精-伊红(HE)染色法观察肝脏病理形态学变化;实时荧光定量聚合酶链式反应(Real-time PCR)和蛋白免疫印迹法(Western blot)法检测肝脏中核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)和半胱氨酸天冬氨酸酶-1(caspase-1)的基因蛋白表达水平。结果:与正常组比,模型组小鼠血清AST、ALT、DBIL、TBIL、IL-1β和IL-18的活性含量均显著升高(P<0.01),肝脏中NLRP3和caspase-1基因蛋白表达明显上调(P<0.01),肝细胞内可见嗜酸性变和炎性细胞浸润;与模型组比,解毒护肝方各剂量组能明显降低血清AST、ALT、DBIL、IL-1β和IL-18的活性或含量以及肝脏中NLRP3和caspase-1基因蛋白表达水平(P<0.01或P<0.05),改善肝脏病理损伤。结论:解毒护肝方可有效防治APAP诱导的小鼠ALI,其机制可能与抑制NLRP3炎症小体介导的炎症反应有关,为临床治疗ALI提供了用药实验依据。Objective:To investigate the protective effect of Jiedu Hugan Recipe on acetaminophen(APAP)-induced acute liver injury(ALI)in mice and its mechanism.Methods:60 C57BL/6N mice were randomly divided into normal group,model group,positive drug group and low,medium and high dose groups of Jiedu Hugan Recipe.At the same time of APAP modeling,corresponding drugs were given by gavage for 14 days.After the experiment,serum and liver tissues were collected to detect alanine aminotransferase(ALT),aspartate aminotransferase(AST),direct bilirubin(DBIL),total bilirubin(TBIL),interleukin-1β(IL-1β)and interleukin-18(IL-18);Hematoxylin eosin(HE)staining was used to observe the pathomorphological changes of liver;The gene and protein expression levels of nucleotide binding oligomerization domain-like receptor protein 3(NLRP3)and caspase-1 in liver were detected by real-time fluorescence quantitative polymerase chain reaction(Real-time PCR)and Western blot.Results:compared with the normal group,the serum AST,ALT,DBIL,TBIL,IL-1βand IL-18 in the model group were significantly increased(P<0.01),NLRP3 and caspase-1 gene protein expression were significantly up-regulated in liver(P<0.01),eosinophilia and inflammatory cell infiltration were observed in hepatocytes;Compared with the model group,each dose group of Jiedu Hugan Recipe can significantly reduce serumAST,ALT,DBIL,TBIL,IL-1βand IL-18 and the expression levels of NLRP3 and caspase-1 genes in liver(P<0.01 or P<0.05).Conclusion:Jiedu Hugan Recipe can effectively prevent and treat APAP-induced ALI in mice,and its mechanism may be related to the inhibition of NLRP3 inflammatory body mediated inflammatory response,which provides an experimental basis for clinical treatment of ALI.

关 键 词：解毒护肝方 药物性肝损伤 药毒 黄疸 对乙酰氨基酚 核苷酸结合寡聚化结构域样受体蛋白3 炎性因子 水飞蓟宾胶囊 

分 类 号：R285.5[医药卫生—中药学]