浏览全部资源
扫码关注微信
1.贵州中医药大学 第二附属医院,贵阳 550003
2.贵州省人民医院,贵阳 550002
3.重庆长寿区人民医院,重庆 401220
4.北京中医药大学,北京 102488
Received:22 June 2021,
Published Online:10 January 2022,
Published:20 January 2023
移动端阅览
游绍伟,易旭,赵琦等.基于NF-κB信号通路探讨萎胃通调汤对大鼠慢性萎缩性胃炎的作用机制[J].中国实验方剂学杂志,2023,29(02):88-97.
YOU Shaowei,YI Xu,ZHAO Qi,et al.Mechanism of Weiwei Tongtiao Decoction Against Chronic Atrophic Gastritis in Rats: Based on NF-κB Signaling Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(02):88-97.
游绍伟,易旭,赵琦等.基于NF-κB信号通路探讨萎胃通调汤对大鼠慢性萎缩性胃炎的作用机制[J].中国实验方剂学杂志,2023,29(02):88-97. DOI: 10.13422/j.cnki.syfjx.20230499.
YOU Shaowei,YI Xu,ZHAO Qi,et al.Mechanism of Weiwei Tongtiao Decoction Against Chronic Atrophic Gastritis in Rats: Based on NF-κB Signaling Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(02):88-97. DOI: 10.13422/j.cnki.syfjx.20230499.
目的
2
探析萎胃通调汤对大鼠慢性萎缩性胃炎(CAG)的干预作用及其可能的机制。
方法
2
90只SD大鼠随机分为正常组,模型组,萎胃通调汤高、中、低剂量干预组,胃复春组6组,每组15只,采用N-甲基-N'-硝基-N-亚硝基胍(MNNG)多因素复合造模法制备CAG大鼠模型。经组织病理学检测鉴定模型制备成功后,给药组分别灌胃给予18、9、4.5 g·kg
-1
·d
-1
的萎胃通调汤及0.45 g·kg
-1
·d
-1
胃复春水溶液,12周后取大鼠胃黏膜组织经苏木素-伊红(HE)染色后,光学显微镜下观察胃黏膜CAG相关病理学表现;采用实时荧光定量聚合酶链式反应(Real-time PCR)、免疫组织化学法(IHC)及蛋白免疫印迹法(Western blot)分别分析大鼠胃黏膜组织核转录因子-
κ
B(NF-
κ
B)信号通路关键指标mRNA及蛋白表达水平。
结果
2
CAG大鼠胃黏膜固有腺体排列和形态极不规则,伴不同程度减少或消失,固有层可见炎性细胞浸润,约48.4%出现肠上皮化生表现。萎胃通调汤处理后显著改善CAG大鼠胃黏膜固有腺体减少与肠化生等病理改变,呈一定的剂量依赖关系。与正常组比较,模型组大鼠胃黏膜组织环氧合酶2(COX-2)、NF-
κ
B p65、白细胞介素(IL)-1
α
、IL-1
β
、IL-10、IL-8
α
、IL-8
β
mRNA及COX-2、NF-
κ
B p65、IL-10蛋白表达水平显著上调(
P
<
0.01)。萎胃通调汤及胃复春干预后CAG大鼠胃黏膜组织COX-2、NF-
κ
B p65、IL-1
α
、IL-1
β
、IL-10、IL-8
α
、IL-8
β
mRNA及COX-2、NF-
κ
B p65、IL-10蛋白表达水平显著下调(
P
<
0.01),其中萎胃通调汤高剂量组相应指标表达水平接近正常组。
结论
2
萎胃通调汤能改善甚至逆转CAG大鼠病变胃黏膜,其作用机制可能与萎胃通调汤下调CAG大鼠胃黏膜组织NF-
κ
B信号通路相关指标mRNA及蛋白表达水平有关。
Objective
2
To explore the effect of Weiwei Tongtiao decoction (WTD) on chronic atrophic gastritis (CAG) rats and the underlying mechanism.
Method
2
A total of 90 SD rats were randomized into normal control group, model group, high-dose, medium-dose, and low-dose WTD groups (18, 9, 4.5 g·kg
-1
·d
-1
WTD, respectively,
ig
), and weifuchun control group (0.45 g·kg
-1
·d
-1
weifuchun aqueous solution,
ig
), with 15 rats in each group. The N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was employed to induced CAG in rats. After the modeling (identified by histopathological examination), the administration began and lasted 12 weeks. Then, gastric mucosa tissues of the rats were collected and stained with hematoxylin and eosin (HE), and the pathological changes of gastric mucosa were observed under the optical microscope. Real-time PCR, immunohistochemistry (IHC), and Western blotting were applied to examine the mRNA and protein expression of indexes in nuclear factor kappa-B (NF-
κ
B) signaling pathway in the gastric mucosa of rats.
Result
2
CAG rats showed irregular arrangement and morphology of the inherent glands in gastric mucosa and the glands decreased or disappeared. In addition, inflammatory cell infiltration was observed in the lamina propria of CAG rats, and about 48.4% presented intestinal metaplasia. WTD significantly alleviated the reduction of the glands and intestinal metaplasia in a dose-dependent manner. Compared with the normal control group, the model group demonstrated increase in the mRNA expression of cyclooxygenase-2 (COX-2), NF-
κ
B p65, interleukin (IL)-1
α
, IL-1
β
, IL-10, IL-8
α
, and IL-8
β
, and protein expression of COX-2, NF-
κ
B p65, and IL-10 (
P
<
0.01). WTD and weifuchun lowered the mRNA expression of COX-2, NF-
κ
B p65, IL-1α, IL-1
β
, IL-10, IL-8
α
, and IL-8
β
, and the protein expression of COX-2, NF-
κ
B p65, and IL-10 in gastric mucosa of CAG rats (
P
<
0.01). The expression of the above indexes after the intervention with high-dose WTD was close to that of the normal control group.
Conclusion
2
WTD can improve or even reverse the diseased gastric mucosa of CAG rats, and the mechanism is the likelihood that WTD down-regulates the mRNA and protein expression of the indexes in NF-
κ
B signaling pathway in gastric mucosa of CAG rats.
房静远 , 杜奕奇 , 刘文忠 , 等 . 中国慢性胃炎共识意见(2017年,上海) [J]. 胃肠病学 , 2017 , 22 ( 11 ): 670 - 687 .
朱永钦 , 朱永苹 , 黄连梅 , 等 . 慢性萎缩性胃炎中医病因病机和辨证分型的临床研究进展 [J]. 中华中医药学刊 , 2017 , 35 ( 2 ): 322 - 325 .
BRAY F , FERLAY J , SOERJOMATARAM I , et al . Global cancer statistics 2018:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries [J]. CA Cancer J Clin , 2018 , 68 ( 6 ): 394 - 424 .
CORREA P . A human-model of gastric carcinogenesis [J]. Can Res , 1988 , 48 ( 13 ): 3554 - 3560 .
谢晶日 , 孙涛 , 张冰 . 益气养阴化瘀解毒方治疗慢性萎缩性胃炎癌前病变的临床观察 [J]. 世界中医药 , 2017 , 12 ( 4 ): 780 - 782 .
朱俊霞 , 史佩玉 , 綦向军 , 等 . 基于网络药理学和分子对接的半夏泻心汤治疗慢性萎缩性胃炎作用机制探讨 [J]. 药物评价研究 , 2021 , 44 ( 1 ): 98 - 110 .
刘珊 , 苏泽琦 , 刘逍遥 , 等 . 基于PubMed和Web of Science数据库对中医药治疗慢性萎缩性胃炎现状的文献分析 [J]. 中国实验方剂学杂志 , 2021 , 27 ( 6 ): 149 - 158 .
游绍伟 , 何鲜平 , 詹亚梅 , 等 . 萎胃通调汤合穴位注射对慢性萎缩性胃炎COX-1、GST-π因子影响的临床研究 [J]. 中华中医药杂志 , 2014 , 29 ( 11 ): 3649 - 3652 .
詹亚梅 , 游绍伟 , 赵琦 , 等 . 萎胃通调汤合穴位注射对慢性萎缩性胃炎COX-2、Ki-67因子的影响 [J]. 中国实验方剂学杂志 , 2014 , 20 ( 18 ): 184 - 187 .
PIMENTELNUNES P , LIBÂNIO D , MARCOSPINTO R , et al . Management of epithelial precancerous conditions and lesions in the stomach (MAPS Ⅱ):European Society of Gastrointestinal Endoscopy (ESGE),European Helicobacter and Microbiota Study Group (EHMSG),European Society of Pathology (ESP), and Sociedade Portuguesa de Endoscopia Digestiva (SPED) guideline update 2019 [J]. Endoscopy , 2019 , 51 ( 4 ): 365 - 388 .
ZHANG J , WANG H . Morroniside protects against chronic atrophic gastritis in rat via inhibiting inflammation and apoptosis [J]. Am J Transl Res , 2019 , 11 ( 9 ): 6016 - 6023 .
LIN Z Q , WANG D X , HONG S S , et al . Effects of Xiangsha Liujunzi decoction on TLR signal pathway in gastric mucosa tissues of rats with Helicobacter pylori-induced chronic atrophic gastritis [J]. Chin J Chin Mater Med , 2016 , 41 ( 16 ): 3078 - 3083 .
ZHANG J , HUANG K , ZHONG G , et al . Acupuncture decreases NF- κ B p65,miR-155,and miR-21 and increases miR-146a expression in chronic atrophic gastritis rats [J]. Evid Based Complement Alternat Med , 2016 , doi: 10.1155/2016/9404629 http://dx.doi.org/10.1155/2016/9404629 .
ZHANG Z , FAN B , LIU F , et al . HOX transcript antisense RNA is elevated in gastric carcinogenesis and regulated by the NF- κ B pathway [J]. J Cell Biochem , 2019 , 120 ( 6 ): 10548 - 10555 .
游绍伟 , 易旭 , 赵琦 , 等 . 萎胃通调汤对大鼠慢性萎缩性胃炎癌前病变及IKK β ,Bcl-2表达的影响 [J]. 中国实验方剂学杂志 , 2021 , 27 ( 6 ): 55 - 61 .
谢晶日 , 王业莉 , 张扬 , 等 . 复合造模法建立大鼠胃癌前病变模型的实验研究 [J]. 中华中医药学刊 , 2013 , 31 ( 11 ): 2341 - 2342 .
ROMERO-ISART N , VASÁK M . Advances in the structure and chemistry of metallothioneins [J]. J Inorg Biochem 2002 , 88 ( 3/4 ): 388 - 396 .
高志华 , 代二庆 , 白玉茹 , 等 . “益气升阳活血法”指导下中药配合针灸、穴位埋线治疗慢性萎缩性胃炎的临床疗效研究 [J]. 中国全科医学 , 2017 , 20 ( 4 ): 492 - 496 .
殷振瑾 , 闫远杰 , 姚乃礼 , 姚乃礼主任医师从邪毒理论辨治慢性萎缩性胃炎经验 [J]. 时珍国医国药 , 2017 , 28 ( 8 ): 2007 - 2008 .
谢晓妹 , 冉静纯 , 赵唯含 , 等 . 基于“虚瘀毒”理论的中医药治疗慢性萎缩性胃炎的Meta分析 [J]. 中华中医药学刊 , 2020 , 38 ( 2 ): 108 - 114 .
田雪娇 , 王彦刚 , 李佃贵 , 等 . 基于数据挖掘的李佃贵教授治疗慢性萎缩性胃炎用药规律 [J]. 中国实验方剂学杂志 , 2016 , 22 ( 21 ): 191 - 196 .
唐传铁 . 苗医药对慢性胃炎认识和治疗初探 [C]//中华中医药学会脾胃病分会. 中华中医药学会脾胃病分会第二十五届全国脾胃病学术交流会论文汇编 . 中华中医药学会脾胃病分会 , 2013 : 4 .
SHRESTHA S , ZHU J , WANG Q , et al .. Melatonin potentiates the antitumor effect of curcumin by inhibiting IKK β /NF- κ B/COX-2 signaling pathway [J]. Int J Oncol , 2017 , 51 ( 4 ): 1249 - 1260 .
WANG X , YU Z , WANG C , et al . Alantolactone,a natural sesquiterpene lactone,has potent antitumor activity against glioblastoma by targeting IKK β kinase activity and interrupting NF- κ B/COX-2 mediated signaling cascades [J]. J Exp Clin Cancer Res , 2017 , 36 ( 1 ): 93 .
MRENA J , WIKSTEN J P , KOKKOLA A , et al . COX-2 is associated with proliferation and apoptosis markers and serves as an independent prognostic factor in gastric cancer [J]. Tumour Biol , 2010 , 31 ( 1 ): 1 - 7 .
LI Y , DAI LP , ZHANG JZ , et al . Cyclooxygenase-2 polymorphisms and the risk of gastric cancer in various degrees of relationship in the Chinese Han population [J]. Oncol Lett , 2012 , 3 ( 1 ): 107 - 112 .
0
Views
22
下载量
3
CSCD
Publicity Resources
Related Articles
Related Author
Related Institution