加味当归芍药散对慢性萎缩性胃炎大鼠JAK2/STAT3信号通路的影响  

Effects of Supplemented Danggui Shaoyao Powder on the JAK2/STAT3 Signaling Pathway in Rats with Chronic Atrophic Gastritis

作　　者：郑晓佳 刘阳 孙建慧[1] 张乃霖 王斌 石芳 刘启泉[1,2] ZHENG Xiaojia;LIU Yang;SUN Jianhui;ZHANG Nailin;WANG Bin;SHI Fang;LIU Qiquan(Hebei University of Traditional Chinese Medicine,Shijiazhuang 050200 Hebei,China;The Affiliated Hospital of Hebei University of Traditional Chinese Medicine,Shijiazhuang 050000 Hebei,China)

机构地区：[1]河北中医学院,河北石家庄050200 [2]河北中医学院附属医院,河北省石家庄050000

出　　处：《中药新药与临床药理》2022年第5期580-587,共8页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：国家中医药管理局2018年全国名中医传承工作室建设项目([2018]119号);河北中医学院科研能力提升重点项目(KTZ2019032);2019年河北省中医院政府资助优才项目(2019061444-3)。

摘　　要：目的探讨加味当归芍药散对慢性萎缩性胃炎(CAG)大鼠JAK2/STAT3信号通路的影响。方法将60只SD大鼠随机分为正常组和造模组,采用N-甲基-N’-硝基-N-亚硝基胍(MNNG)复合法建立CAG大鼠模型;将造模成功的大鼠随机分为模型组、摩罗丹组(0.5 g·kg^(-1))和加味当归芍药散高、中、低剂量组(16、8、4 g·kg^(-1)),每组10只;灌胃给药,每日1次,连续8周。采用HE染色法观察大鼠胃黏膜组织病理变化;ELISA法检测胃黏膜组织中白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)的含量;Real-time PCR法检测胃黏膜组织JAK2、STAT3 mRNA表达水平;Western Blot法检测胃黏膜组织JAK2、p-JAK2、STAT3、p-STAT3蛋白表达水平;免疫组化法检测胃黏膜组织中Bcl-2、Bcl-xl、Bax、BAD蛋白表达水平。结果与正常组比较,模型组大鼠胃黏膜萎缩明显;胃黏膜组织中的IL-6、TNF-α含量显著升高(P<0.01);STAT3 mRNA表达水平显著升高(P<0.01);p-JAK2/JAK2、p-STAT3/STAT3值显著升高(P<0.01);Bax、Bad蛋白表达水平显著升高(P<0.01),Bcl-2、Bcl-xl蛋白表达水平显著降低(P<0.01)。与模型组比较,当归芍药散给药组大鼠的胃黏膜萎缩明显改善;胃黏膜组织中的IL-6、TNF-α含量明显降低(P<0.05,P<0.01);STAT3 mRNA表达显著下调(P<0.01);p-JAK2/JAK2、p-STAT3/STAT3值显著降低(P<0.01);Bax、Bad蛋白表达水平显著降低(P<0.01),Bcl-2、Bcl-xl蛋白表达水平显著升高(P<0.01)。结论加味当归芍药散能够明显改善CAG大鼠的胃黏膜萎缩状态,可能与下调JAK2/STAT3信号通路,减少炎症因子生成及细胞凋亡有关。Objective To investigate the effects of supplemented Danggui Shaoyao Powder on the Janus protein tyrosine kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)signaling pathway in the gastric tissue of rats with chronic atrophic gastritis(CAG).Methods Sixty SD rats were randomly divided into normal and modeling groups,and the CAG rat model was established using the N-methyl-N’-nitro-N-nitrosoguanidine(MNNG)compound method;the successfully modeled rats were randomly divided into the modeling group,the Morodan group(0.5 g·kg^(-1))and the high-,medium-and low-dose of supplemented Danggui Shaoyao Powder groups(16,8 and 4 g·kg^(-1)),10 rats in each group;The rats were administered by gavage,once daily for 8 continuous weeks.The histopathological changes in the gastric mucosa of rats were observed by the HE staining;the contents of interleukin 6(IL-6)and tumor necrosis factorα(TNF-α)in the gastric mucosa of rats were detected by the ELISA;the mRNA expression levels of JAK2 and STAT3 in the gastric mucosa of rats were detected by the Real-time PCR method;the protein expression levels of JAK2 and p-JAK3 in the gastric mucosa of rats were detected by the Western Blot method.The protein expression levels of JAK2,p-JAK2,STAT3 and p-STAT3 in gastric mucosa tissues were measured by the Real-time PCR method;the protein expression levels of Bcl-2,Bcl-xl,Bax and BAD in gastric mucosa tissues were measured by Western Blot method.Results Compared with the normal group,the gastric mucosa of rats in the model group was significantly atrophied;the content of IL-6 and TNF-αin the mucosal tissue was significantly increased(P<0.01);the mRNA expression level of STAT3 was significantly increased(P<0.01);the values of p-JAK2/JAK2 and p-STAT3/STAT3 were significantly increased(P<0.01);the protein expression levels of Bax and Bad were significantly increased(P<0.01)and the protein expression levels of Bcl-2 and Bcl-xl were significantly decreased(P<0.01).Compared with the model group,the atrophy of gastric mucosa of

关 键 词：加味当归芍药散 慢性萎缩性胃炎 JAK2/STAT3信号通路 炎症因子 凋亡 大鼠 

分 类 号：R285.5[医药卫生—中药学]