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[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].

作者信息

Zheng Xiao-Jia, Chen Ping-Ping, Liu Yang, Sun Jian-Hui, Zhang Nai-Lin, Wang Bin, Liu Qi-Quan

机构信息

Hebei University of Chinese Medicine Shijiazhuang 050020, China.

Hebei University of Chinese Medicine Shijiazhuang 050020, China the First Affiliated Hospital of Hebei University of Chinese Medicine Shijiazhuang 050011, China.

出版信息

Zhongguo Zhong Yao Za Zhi. 2022 Aug;47(15):4128-4135. doi: 10.19540/j.cnki.cjcmm.20220325.701.

Abstract

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.

摘要

本研究旨在探讨加味当归芍药散对慢性萎缩性胃炎(CAG)大鼠胃组织中细胞因子信号转导抑制因子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、摩罗丹组以及加味当归芍药散高、中、低剂量组。除正常组外,其他组大鼠用N-甲基-N'-硝基-N-亚硝基胍(MNNG)处理以建立CAG模型。造模12周后,各组大鼠通过灌胃给予相应药物,持续8周。末次给药后,通过苏木精-伊红(HE)染色观察大鼠胃黏膜的组织病理学变化。采用酶联免疫吸附测定(ELISA)法测定血清白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)和C反应蛋白(CRP)水平。通过实时聚合酶链反应(PCR)测定SOCS3和TLR4的mRNA水平。采用蛋白质印迹法检测大鼠胃组织中SOCS3、TLR4、Janus激酶2(JAK2)、磷酸化JAK2(p-JAK2)、信号转导和转录激活因子3(STAT3)及磷酸化STAT3(p-STAT3)的蛋白水平。采用免疫组织化学方法检测大鼠胃组织中核因子κB(NF-κB)、髓样分化因子88(MyD88)、NOD样受体蛋白3(NLRP3)、B细胞淋巴瘤-2(Bcl-2)、Bax和Bad的蛋白水平。结果显示,加味当归芍药散减轻了大鼠胃黏膜萎缩,显著降低了大鼠血清中IL-6、TNF-α和CRP水平,上调了大鼠胃组织中SOCS3的mRNA水平,下调了TLR4的mRNA水平。此外,加味当归芍药散上调了SOCS3的蛋白水平,下调了TLR4、p-JAK2、p-STAT3、NF-κB、MyD88、NLRP3、Bax和Bad的蛋白水平,并促进了Bcl-2蛋白的表达。因此,加味当归芍药散可能通过调节SOCS3/TLR4信号通路减轻大鼠胃黏膜萎缩。

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