柴芩承气汤通过抑制TLR4/NF-κB p65通路减轻小鼠重症急性胰腺炎并发肝损伤  

Chaiqinchengqi decoction alleviates liver injury during severe acute pancreatitis in mice via inhibition of TLR4/NF-κB p65 pathway

作　　者：党琳[1] 宋亮 张晓芹[1] 许小凡 张红[1,2] DANG Lin;SONG Liang;ZHANG Xiao-qin;XU Xiao-fan;ZHANG Hong(College of Basic Medicine,Shaanxi University of Chinese Medicine,Xianyang Shaanxi 712046,China;Medical Experiment Center,Shaanxi University of Chinese Medicine,Xianyang Shaanxi 712046,China)

机构地区：[1]陕西中医药大学基础医学院,陕西咸阳712046 [2]陕西中医药大学医学科研实验中心,陕西咸阳712046

出　　处：《中国药理学通报》2020年第1期134-139,共6页Chinese Pharmacological Bulletin

基　　金：胰、肝疾病的分子机制及中西医防治创新团队(2019-YL14);陕西省教育厅专项科研计划项目(No 16JK1197);陕西省科技厅社会发展科技攻关项目(No 2015SF222)

摘　　要：目的基于TLR4/NF-κB p65信号通路探讨柴芩承气汤(chaiqinchengqi decoction,CQCQD)对小鼠重症急性胰腺炎(severe acute pancreatitis,SAP)并发肝损伤的保护机制。方法昆明小鼠36只,随机分为3组(n=12),即对照组(Control),重症急性胰腺炎模型组(SAP)和柴芩承气汤治疗组(SAP+CQCQD)。腹腔注射20%L-精氨酸(3.3 g·kg-1,2次,间隔1 h)建立SAP模型,治疗组给予柴芩承气汤灌胃(19 g·kg-1·d-1)。造模后72 h观察胰腺、肝脏组织病理变化,检测血清内毒素含量,肝组织TLR4、p-NF-κB p65蛋白表达,及肝内炎性因子水平。结果与Control组相比,SAP组胰腺和肝脏可见明显的病理损伤,血清内毒素含量增多,肝组织TLR4、p-NF-κB p65表达增加,IL-6、TNF-α、MIP-1αmRNA水平升高。与SAP组相比,柴芩承气汤组胰腺和肝脏组织病理损伤减轻,血清内毒素含量降低,肝组织TLR4、p-NF-κB p65表达和IL-6、TNF-α、MIP-1α mRNA水平减少。 结论 柴芩承气汤可能通过抑制肝组织TLR4/NF-κB p65通路活化,降低促炎因子水平,从而减轻小鼠SAP并发肝损伤。Aim To explore the protective mechanisms of Chaiqinchengqi decoction(CQCQD)on liver injury during severe acute pancreatitis(SAP)based on TLR4/NF-κB p65 pathway.Methods Thirty-six KM mice were randomly divided into control group(Control),SAP and SAP+CQCQD(treatment group)(n=12).The mice in SAP group were injected with 20%L-arginine intraperitoneally(3.3 g·kg-1,2 times,1 h interval).The mice in SAP+CQCQD group were intragastrically administered with Chaiqinchengqi decoction(19 g·kg-1·d-1)following induction of SAP.Histopathological changes of pancreas and liver were observed 72 hours after model establishment.The endotoxin in serum was tested,and the TLR4 and p-NF-κB p65 expression,as well as some inflammatory cytokines in liver was detected.Results Compared to control group,the pathological damages of the pancreas and liver in SAP group were aggravated,serum endotoxin increased,the expression of TLR4 and p-NF-κB p65 in liver increased,and IL-6,TNF-αand MIP-1αmRNA in liver were significantly elevated.Compared to SAP group,the intervention of CQCQD partially relieved the pathological damages of the pancreas and liver,reduced the endotoxin in serum,and decreased the expression of TLR4 and p-NF-κB p65,as well as IL-6,TNF-αand MIP-1αmRNA in the liver.Conclusion CQCQD appears to protect liver injury during SAP via inhibiting TLR4/NF-κB p65 activation,then decreasing cytokines and chemokines.

关 键 词：柴芩承气汤 内毒素 TLR4 NF-ΚB 重症急性胰腺炎 肝损伤 

分 类 号：R289[医药卫生—方剂学] R322[医药卫生—中药学]