文献类型：期刊文献

中文题名：基于TLR4/MYD88信号通路探讨大黄牡丹汤对急性胰腺炎大鼠模型的保护作用

英文题名：Study on the protective effect of Dahuang Mudan Decoction on rat model of acute pancreatitis based on TLR4/MYD88 signaling pathway

作者：宋冰[1,2];汪永锋[2];余四九[1];张延英[2];康万荣[2]

第一作者：宋冰

机构：[1]甘肃农业大学,兰州730070;[2]甘肃中医药大学,甘肃省实验动物行业技术中心,兰州730000

第一机构：甘肃农业大学,兰州730070

年份：2021

卷号：29

期号：1

起止页码：17

中文期刊名：中国实验动物学报

外文期刊名：Acta Laboratorium Animalis Scientia Sinica

收录：CSTPCD;;北大核心:【北大核心2020】；CSCD:【CSCD2021_2022】；

基金：国家自然科学基金(81760828);甘肃省中医药管理局科研课题(GZK-2019-26)。

语种：中文

中文关键词：TLR4/MYD88信号通路;大黄牡丹汤;急性胰腺炎;大鼠;

外文关键词：TLR4/MyD88 signal pathway;Dahuang Mudan Decoction;acute pancreatitis;rat;

摘要：目的基于TLR4/MYD88信号通路研究大黄牡丹汤对逆行性胰胆管注射法制作急性胰腺炎(acute pancreatitis,AP)大鼠模型的保护作用。方法SPF级Wistar大鼠96只,按照随机数字表法分为:假手术组、AP模型观察组、奥曲肽阳性对照组、大黄牡丹汤高、中、低剂量组,除假手术组经胰胆管逆行注射生理盐水,其余各组均采用经胰胆管逆行注射5%牛磺胆酸钠溶液造模,给与药物干预6 d。观察大鼠一般生存状况;测定血清淀粉酶(AMS)、谷丙转氨酶(ALT)、谷草转氨酶(AST)含量;HE观察胰腺病理组织改变;RT-PCR、Westen Blot、IHC法检测胰腺组织TLR4、MYD88、IRAK-2、IRAK-4基因蛋白表达水平;ELISA法检测胰腺组织中炎性因子IL-2、iNOS、IFN-γ含量。结果(1)与假手术组比较,AP模型观察组大鼠一般生存状况相对较差,血清淀粉酶(AMS)、谷丙转氨酶(ALT)、谷草转氨酶(AST)均显著升高,镜下可见胰腺组织结构散乱,坏死、充血严重,胰腺组织中TLR4、MYD88、IRAK-2、IRAK-4基因蛋白表达水平均显著升高,胰腺组织匀浆液中IL-2、iNOS、IFN-γ含量均显著升高,差异具有统计学意义(P<0.05);(2)干预后,各治疗组大鼠一般生存状况有不同程度改善,血清淀粉酶(AMS)、谷丙转氨酶(ALT)、谷草转氨酶(AST)均下降,镜下间质性水肿以及坏死灶明显改善,胰腺组织中TLR4、MYD88、IRAK-2、IRAK-4基因蛋白表达水平均下降,胰腺组织匀浆液中IL-2、iNOS、IFN-γ含量均下降,其中尤以大黄牡丹汤高剂量组显著,差异具有统计学意义(P<0.05)。结论大黄牡丹汤改善急性胰腺炎大鼠胰腺损伤,其作用机制可能与抑制TLR4/MYD88信号通路有关。
Objective Based on the TLR4/MYD88 signaling pathway to study the protective effect of Dahuang Mudan Decoction on the rat model of acute pancreatitis(AP)made by retrograde pancreaticobiliary duct injection.Methods 96 Wistar rats(SPF grade)were divided into:sham operation group,AP model observation group,octreotide positive control group,Dahuang Mudan Decoction high,medium and low dose groups according to the random number table method.Except for the sham operation group,which was injected by retrograde with normal saline through the pancreaticobiliary duct,the other groups were modeled by retrograde injection of 5%sodium taurocholate solution through the pancreaticobiliary duct,followed by drug intervention for 6 days.To observe the general living conditions of rats,to measure the contents of serum amylase(AMS),alanine aminotransferase(ALT)and aspartate aminotransferase(AST),The expression levels of TLR4,MyD88,IRAK-4 and IRAK-4 were detected by RT-PCR,Westen Blot and IHC,and the contents of IL-2,iNOS and IFN-γwere detected by ELISA.Results(1)Compared with the sham operation group,the rats in the AP model observation group had a relatively poor general survival condition,a significant increase in serum amylase(AMS),alanine aminotransferase(ALT),glutamic oxaloacetase(AST).Under the microscope,the pancreatic tissue structure was scattered,necrosis and congestion were serious.The expression levels of TLR4,MyD88,IRAK-2 and IRAK-4 gene protein in pancreatic tissue were significantly increased,and the contents of IL-2,iNOS and IFN-γin pancreatic tissue homogenate were significantly increased(P<0.05).(2)After intervention,the general living conditions of the rats in the treatment group were improved in different degrees,serum amylase(AMS),alanine aminotransferase(ALT)and aspartate aminotransferase(AST)were decreased,interstitial edema and necrotic foci were significantly improved under the microscope,the expression levels of TLR4,MyD88,irak-2 and IRAK-4 gene protein in pancreatic tissue were decreased,and the contents of IL-2,iNOS and IFN-γin pancreatic tissue homogenate were decreased,especially in the large dose group of Dahuang Mudan decoction,the difference was statistically significant(P<0.05).Conclusions Dahuang Mudan decoction can improve pancreatic injury in rats with acute pancreatitis,and its mechanism may be related to the inhibition of TLR4/MyD88 signaling pathway.