加味当归芍药散对慢性萎缩性胃炎大鼠SOCS3/TLR4信号通路的影响  

Effect of modified Danggui Shaoyao Powder on SOCS3/TLR4 signaling pathway in rats with chronic atrophic gastritis

作　　者：郑晓佳 陈苹苹[1] 刘阳 孙建慧[1] 张乃霖 王斌 刘启泉[1,2] ZHENG Xiao-jia;CHEN Ping-ping;LIU Yang;SUN Jian-hui;ZHANG Nai-lin;WANG Bin;LIU Qi-quan(Hebei University of Chinese Medicine,Shijiazhuang 050020,China;the First Afiliated Hospital of Hebei University of Chinese Medicine,Shijiazhuang 050011,China)

机构地区：[1]河北中医学院,河北石家庄050020 [2]河北中医学院第一附属医院,河北石家庄050011

出　　处：《中国中药杂志》2022年第15期4128-4135,共8页China Journal of Chinese Materia Medica

基　　金：国家中医药管理局2018年全国名老中医传承工作室建设项目(国中医药办人教函[2018]119号);2019年河北省中医院政府优才项目(2019061444-3)。

摘　　要：探讨加味当归芍药散对慢性萎缩性胃炎(CAG)大鼠胃组织细胞信号转导抑制因子3(SOCS3)/Toll样受体4(TLR4)信号通路的影响。将60只SPF级SD大鼠随机分为正常组,模型组,摩罗丹组,加味当归芍药散高、中、低剂量组,除了正常组外,其余各组大鼠采用N-甲基-N′-硝基-N-亚硝基胍(MNNG)复合法建立慢性萎缩性胃炎大鼠模型。造模12周,开始灌胃给予各组大鼠相应药物,给药持续8周。末次给药后,取材。HE染色观察大鼠胃黏膜组织病理学变化,ELISA(enzyme-linked immunosorbent assay)检测IL-6、TNF-α和CRP的含量,实时荧光定量聚合酶链式反应(real-time PCR)检测SOCS3、TLR4基因表达水平,Western blot法检测SOCS3、TLR4、JAK2、p-JAK2、STAT3、p-STAT3蛋白表达水平。免疫组化法检测大鼠胃组织中NF-κB、MyD88、NLRP3、Bcl-2、Bax、Bad蛋白表达水平。加味当归芍药散各剂量组大鼠胃黏膜萎缩减轻,大鼠血清中IL-6、TNF-α和CRP水平显著降低,大鼠胃组织中SOCS3 mRNA水平升高,TLR4 mRNA水平降低,SOCS3蛋白水平升高,TLR4、p-JAK2、p-STAT3蛋白表达降低,NF-κB、MyD88、NLRP3、Bax、Bad蛋白表达水平减弱,Bcl-2蛋白表达水平增强。加味当归芍药散能够明显改善CAG大鼠胃黏膜萎缩状态,其机制可能与干预SOCS3/TLR4通路相关。This study aims to investigate the effect of modified Danggui Shaoyao Powder on the suppressor of cytokine signaling 3(SOCS3)/Toll-like receptor 4(TLR4)signaling pathway in gastric tissue of rats with chronic atrophic gastritis(CAG).Sixty SPF-grade SD rats were randomly assigned into the normal group,model group,Moluo Pills group,and high-,medium-,and low-dose groups of modified Danggui Shaoyao Powder.The rats in other groups except the normal group were treated with N-methyl-N′-nitro-N-nitrosoguanidine(MNNG)to establish the CAG model.After 12 weeks of modeling,the rats in each group were administrated with corresponding drugs by gavage for 8 weeks.After the last administration,the histopathological changes of rat gastric mucosa were observed via hematoxylin-eosin(HE)staining.The serum levels of IL-6,TNF-α,and CRP were determined by enzyme-linked immunosorbent assay(ELISA).The mRNA levels of SOCS3 and TLR4 were determined by real-time PCR.The protein levels of SOCS3,TLR4,JAK2,p-JAK2,STAT3,and p-STAT3 in rat gastric tissue were measured by Western blot.Immunohistochemical method was employed to determine the protein levels of NF-κB,MyD88,NLRP3,Bcl-2,Bax,and Bad in rat gastric tissue.The results showed that modified Danggui Shaoyao Powder alleviated gastric mucosal atrophy of rats,significantly lowered the levels of IL-6,TNF-α,and CRP in rat serum,up-regulated the mRNA level of SOCS3,and down-regulated the mRNA level of TLR4 in rat gastric tissue.Furthermore,modified Danggui Shaoyao Powder up-regulated the protein level of SOCS3,down-regulated the protein levels of TLR4,p-JAK2,p-STAT3,NF-κB,MyD88,NLRP3,Bax,and Bad,and promoted the expression of Bcl-2 protein.Therefore,modified Danggui Shaoyao Powder may mitigate the gastric mucosal atrophy of rats by regulating the SOCS3/TLR4 signaling pathway.

关 键 词：加味当归芍药散 慢性萎缩性胃炎 细胞信号转导抑制因子3/Toll样受体4信号通路 

分 类 号：R285.5[医药卫生—中药学]