基于Nrf2/HO-1通路探讨大承气汤治疗小鼠重症急性胰腺炎并发急性肾损伤作用机制  

Exploration on the Mechanism of Dachengqi Decoction in Treating Severe Acute Pancreatitis Complicated with Acute Kidney Injury in Mice Based on Nrf2/HO-1 Pathway

作　　者：吴月 王启蒙 孔婧[1] 刘宇洋 宇萌 王晓素[1] 李英[1] WU Yue;WANG Qimeng;KONG Jing;LIU Yuyang;YU Meng;WANG Xiaosu;LI Ying(Yueyang Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai 200437,China;Longhua Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200032,China)

机构地区：[1]上海中医药大学附属岳阳中西医结合医院,上海200437 [2]上海中医药大学附属龙华医院,上海200032

出　　处：《中国中医药信息杂志》2024年第5期55-60,共6页Chinese Journal of Information on Traditional Chinese Medicine

基　　金：上海市卫生健康委员会中医药科研项目(2020JP022);上海市申康医院发展中心中西医临床协作试点建设项目(ZY2018-2020-FWTX-1004);国家自然科学基金(82004264)。

摘　　要：目的探讨大承气汤治疗小鼠重症急性胰腺炎(SAP)并发急性肾损伤(AKI)的可能作用机制。方法采用胆胰管逆行注射3.5%牛磺胆酸钠制备SAP小鼠模型。将30只C57BL/6小鼠分为假手术组、模型组和大承气汤组,大承气汤组术后5、13、21 h予大承气汤灌胃,假手术组和模型组予生理盐水灌胃。术后24h观察小鼠一般状况,检测血清淀粉酶(AMY)、肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6、IL-1β、血肌酐(SCr)、血尿素氮(BUN)、超氧化物歧化酶(SOD)、丙二醛(MDA)含量;观察小鼠胰腺及肾组织形态,检测肾组织核因子E2相关因子2(Nrf2)、血红素氧合酶1(HO-1)mRNA及蛋白表达。结果与假手术组比较,模型组小鼠精神萎靡,反应差,血清AMY、TNF-α、IL-1β、IL-6、SCr、BUN、MDA含量明显升高(P<0.001),SOD含量明显降低(P<0.001);胰腺组织和肾组织出现细胞水肿、坏死及炎性细胞浸润等变化,病理评分明显升高(P<0.001),肾组织Nrf2 mRNA和蛋白表达明显升高(P<0.01,P<0.05),HO-1蛋白表达明显升高(P<0.01)。与模型组比较,大承气汤组小鼠整体状态尚可,血清AMY、TNF-α、IL-1β、IL-6、SCr、BUN、MDA含量明显降低(P<0.001,P<0.01),SOD含量明显升高(P<0.05);胰腺组织和肾组织损伤均减轻,病理评分明显降低(P<0.05,P<0.001),肾组织Nrf2、HO-1 mRNA和蛋白表达明显升高(P<0.05,P<0.01)。结论大承气汤能减轻SAP小鼠全身炎症反应,改善小鼠胰腺和肾组织病理损伤,其作用机制可能与激活Nrf2/HO-1信号通路、调节氧化应激反应相关。Objective To investigate the possible mechanism of Dachengqi Decoction in the treatment of severe acute pancreatitis(SAP)complicated with acute kidney injury(AKI).Methods SAP mouse model was prepared by retrograde injection of 3.5%sodium taurocholate into bile pancreatic duct.Thirty C57BL/6 mice were divided into sham-operation group,model group and the Dachengqi Decoction group.Dachengqi Decoction group was given Dachengqi Decoction for gavage at 5,13 and 21 hours after operation,the sham-operation group and the model group were given normal saline.The general condition of mice was observed 24 h after operation.The levels of AMY,TNF-α,IL-6,IL-1β,SCr,BUN,SOD and MDA in serum were detected.The morphology of pancreas and kidney was observed,and the mRNA and protein expressions of Nrf2 and HO-1 in renal tissue were detected.Results Compared with the sham operation group,the mice in the model group were sluggish and had poor response,and the contents of serum AMY,TNF-α,IL-1β,IL-6,SCr,BUN and MDA were significantly increased(P<0.001),while the content of SOD was significantly decreased(P<0.001);cell edema,necrosis and inflammatory cells infiltration were observed in pancreas and renal tissue,and the pathological scores were significantly increased(P<0.001),and the expression of Nrf2 mRNA and protein in renal tissue were significantly increased(P<0.01,P<0.05),and HO-1 protein expression was significantly increased(P<0.01).Compared with the model group,the overall condition of the mice in the Dachengqi decoction group was acceptable,the contents of serum AMY,TNF-α,IL-1β,IL-6,SCr,BUN and MDA in mice were significantly decreased(P<0.001,P<0.01),the contents of SOD increased significantly(P<0.05);the pancreas and renal tissue injuries were alleviated,the pathological scores were significantly decreased(P<0.05,P<0.001),the expressions of Nrf2 and HO-1 mRNA and protein in renal tissue significantly increased(P<0.05,P<0.01).Conclusion Dachengqi Decoction can alleviate the systemic inflammatory response and improve the p

关 键 词：重症急性胰腺炎 急性肾损伤 大承气汤 Nrf2/HO-1通路 小鼠 

分 类 号：R285.5[医药卫生—中药学]