中国药理学通报2024,Vol.40Issue(8):1489-1494,6.DOI:10.12360/CPB202404083
基于RIPK1/RIPK3/MLKL信号通路探讨清解化攻方对重症急性胰腺炎大鼠胰腺坏死性凋亡的影响
Effect of Qingjie Huagong decoction on pancreatic necrotic apoptosis in rats with severe acute pancreatitis based on RIPK1/RIPK3/MLKL signaling pathway
摘要
Abstract
Aim To explore the therapeutic effect of Qingjie Huagong decoction in regulating RIPK1/RIPK3/MLKL signaling pathway on pancreatic necrotic apoptosis in rats with severe acute pancreatitis(SAP)and the underlying mechanism.Methods The SAP rat model was established by retrograde pancreaticobili-ary injection of sodium taurocholate,and the sham-op-eration group,the model group,the group with differ-ent dosages of Qingjie Huagong decoction and the posi-tive control group were set up respectively.The group with different dosages of Qingjie Huagong decoction was given low,medium and high dosages of traditional Chinese medicine in the gastric gavage,the positive control group was given ulinastatin drug intervention,and the sham-operation and the model group were giv-en physiological saline in the gastric gavage;HE stai-ning was applied to observe pancreatic pathology;ELISA was used to measure the serum levels of α-am-ylase,IL-1β,IL-6,and TNF-α;immunohistochemis-try and Western blot were employed to determine the RIPK1,RIPK3,MLKL protein expression in rat pan-creatic tissue;and qRT-PCR was utilized to detect the transcription levels of R1PK1,RIPK3 and MLKL mR-NA in rat pancreatic tissue.Results Compared with the sham-operated group,the model group showed dif-fuse necrosis of pancreatic acinar cells,obvious inter-lobular septal edema,inflammatory cell infiltration,significantly higher levels of α-amylase,IL-1β,IL-6,and TNF-α(P<0.01),and significantly higher ex-pression levels of RIPK1,RIPK3,and MLKL proteins and mRNAs(P<0.01)in the model group;com-pared with the model group,the Qingjie Huagong de-coction dose groups and positive control group signifi-cantly improved pancreatic histopathology,reduced pancreatic tissue necrosis and apoptosis,lowered the expression levels of α-amylase,IL-1 β,IL-6 and TNF-α(P<0.01),and reduced the expression levels of RIPK1,RIPK3,and MLKL proteins and mRNAs(P<0.01).Conclusions Qingjie Huagong decoction may improve the necrotic apoptosis of pancreatic tissue by regulating the RIPK1/RIPK3/MLKL signaling path-way,thus playing a role in protecting pancreatic tissue and slowing down the progression of the disease.关键词
重症急性胰腺炎/清解化攻方/RIPK1/RIPK3/MLKL信号通路/坏死性凋亡/胰腺/作用机制Key words
severe acute pancreatitis/Qingjie Hua-gong decoction/RIPK1/RIPK3/MLKL signaling path-way/necroptosis/pancreas/mechanism of action分类
医药卫生引用本文复制引用
朱晓东,冯敏超,刘锟荣,班莹,唐曦平,陈国忠..基于RIPK1/RIPK3/MLKL信号通路探讨清解化攻方对重症急性胰腺炎大鼠胰腺坏死性凋亡的影响[J].中国药理学通报,2024,40(8):1489-1494,6.基金项目
国家自然科学基金资助项目(No 82160890) (No 82160890)
广西自然科学基金面上项目(No 2024GXNSFAA010246) (No 2024GXNSFAA010246)
国家中医优势专科建设项目(No 2024010) (No 2024010)
广西中医药大学引进博士科研启动基金项目(No 2022BS029) (No 2022BS029)
广西自然科学基金面上项目(No 2020GXNSFAA297062) (No 2020GXNSFAA297062)