文献类型：期刊文献

中文题名：香砂六君子汤对慢性萎缩性胃炎的作用

英文题名：Role of Xiangsha Liujunzi decoction on chronic atrophic gastritis

作者：袁晓梅[1,2];安耀荣[1,2];成映霞[5,6];段永强[5,6];张延英[1,3];白敏[1,3];彭月[1,4];刘自由[1,4]

第一作者：袁晓梅

机构：[1]甘肃中医药大学基础医学院,甘肃兰州730000;[2]甘肃中医药大学甘肃省中医方药挖掘与创新转化重点实验室,甘肃兰州730000;[3]甘肃中医药大学甘肃省实验动物行业技术中心,甘肃兰州730000;[4]甘肃中医药大学甘肃省中药新产品创制工程实验室,甘肃兰州730000;[5]宁夏医科大学中医学院,宁夏回族自治区银川750004;[6]宁夏医科大学附属中医医院,宁夏回族自治区吴忠751100

第一机构：甘肃中医药大学基础医学院（敦煌医学研究所）

年份：2025

卷号：41

期号：10

起止页码：1415

中文期刊名：中国临床药理学杂志

外文期刊名：The Chinese Journal of Clinical Pharmacology

收录：;北大核心:【北大核心2023】；

基金：国家自然科学基金地区基金资助项目(81760830,82060828);国家中医药管理局重点学科建设基金资助项目(国中医药人教函[2023]85号);宁夏医科大学中医学院一流学科建设基金资助项目(ZY0019110305)。

语种：中文

中文关键词：香砂六君子汤;慢性萎缩性胃炎;炎症;肿瘤坏死因子受体相关因子6;NOD样受体蛋白3炎症小体

外文关键词：Xiangsha Liujunzi decoction;chronic atrophic gastritis;inflammation;tumor necrosis factor receptor-associated factor 6;NOD-like receptor protein 3 inflammasome

摘要：目的基于肿瘤坏死因子受体相关因子6(TRAF6)激活NOD样受体蛋白3(NLRP3)炎症小体诱导细胞焦亡,探讨香砂六君子汤治疗慢性萎缩性胃炎的作用机制。方法除空白组外其他组大鼠用N-甲基-N′-硝基-N-亚硝基胍复合法建立慢性萎缩性胃炎大鼠模型,建模成功后将成模大鼠按照随机数表法分为模型组、叶酸组和低、中、高剂量实验组。低、中、高剂量实验组分别以3、6和12 g·kg^(-1)香砂六君子汤生药液灌胃,叶酸组以2 mg·kg^(-1)灌胃,空白组和模型组均给予0.9%NaCl,持续干预90 d。用酶联免疫试验法检测大鼠胃黏膜组织中白细胞介素1β(IL-1β)和IL-18含量,用蛋白质印迹法检测TRAF6、NLRP3、胱天蛋白酶-1(Caspase-1)和焦孔素-D(GSDMD)蛋白的表达水平。结果空白组、模型组、叶酸组与低、中、高剂量实验组大鼠胃黏膜组织内IL-18水平分别为(119.85±18.60)、(164.69±18.64)、(142.37±18.74)、(139.59±18.54)、(132.95±17.99)和(128.93±18.90)pg·mL^(-1),IL-1β水平分别为(43.80±5.10)、(56.14±5.49)、(48.40±5.27)、(46.11±7.58)、(45.81±6.20)和(44.99±7.42)pg·mL^(-1),TRAF6蛋白相对表达水平分别为0.49±0.06、1.19±0.14、0.78±0.06、0.84±0.10、0.78±0.08和0.55±0.06,NLRP3蛋白相对表达水平分别为0.40±0.06、1.22±0.12、0.81±0.09、0.89±0.07、0.65±0.07和0.47±0.10,Caspase-1蛋白相对表达水平分别为0.39±0.06、1.12±0.12、0.80±0.09、0.92±0.12、0.87±0.09和0.61±0.08,GSDMD蛋白相对表达水平分别为0.34±0.05、1.26±0.22、0.90±0.16、0.69±0.07、0.53±0.12和0.41±0.08。模型组的上述指标与空白组比较,叶酸组和低、中、高剂量实验组的上述指标与模型组比较,在统计学上差异均有统计学意义(均P<0.05)。结论香砂六君子汤能够有效改善慢性萎缩性胃炎模型大鼠胃黏膜组织病变情况,其作用机制可能与抑制TRAF6介导NLRP3炎症小体活化有关。
Objective To investigate the mechanism of action of Xiangsha Liujunzi decoction in the treatment of chronic atrophic gastritis based on the activation of NOD-like receptor protein 3(NLRP3)inflammasome by tumor necrosis factor receptor-associated factor 6(TRAF6)to induce cellular pyroptosis.Methods Except for the blank group,a rat model of chronic atrophic gastritis was established in the other groups of rats using the N-methyl-N'-nitro-N-nitrosoguanidine composite method.After successful modeling,the modeled rats were divided into model group,folic acid group and experimental-L,-M,-H groups according to the random number table method.The experimental-L,-M,-H groups were intragastrically administered with 3,6 and 12 g·kg^(-1) of raw Xiangsha Liujunzi decoction solution,respectively;the folic acid group was intragastrically administered with 2 mg·kg^(-1),the blank group and model group were given 0.9%NaCl.The intervention continued for 90 days.The enzyme-linked immunosorbent assay was used to detect the contents of interleukin-1β(IL-1β)and IL-18 in the rat gastric mucosa tissue.Western blot was used to detect the protein expression levels of TRAF6,NLRP3,Caspase-1 and gasdermin-D(GSDMD).Results The levels of IL-18 in the gastric mucosa tissue of rats in the blank group,model group,folic acid group,and experimental-L,-M,-H groups were(119.85±18.60),(164.69±18.64),(142.37±18.74),(139.59±18.54),(132.95±17.99)and(128.93±18.90)pg·mL^(-1),respectively;the levels of IL-1βwere(43.80±5.10),(56.14±5.49),(48.40±5.27),(46.11±7.58),(45.81±6.20)and(44.99±7.42)pg·mL^(-1),respectively;the relative expression levels of TRAF6 protein were 0.49±0.06,1.19±0.14,0.78±0.06,0.84±0.10,0.78±0.08 and 0.55±0.06,respectively;the relative expression levels of NLRP3 protein were 0.40±0.06,1.22±0.12,0.81±0.09,0.89±0.07,0.65±0.07 and 0.47±0.10,respectively;the relative expression levels of Caspase-1 protein were 0.39±0.06,1.12±0.12,0.80±0.09,0.92±0.12,0.87±0.09 and 0.61±0.08,respectively;the relative expression levels of GSDMD protein were 0.34±0.05,1.26±0.22,0.90±0.16,0.69±0.07,0.53±0.12 and 0.41±0.08,respectively.There were statistically significant differences in the above indicators between the model group and the blank group,and between the folic acid group and the experimental-L,-M,-H groups and the model group(all P<0.05).Conclusion Xiangsha Liujunzi decoction is able to effectively improve the general condition and gastric mucosal histopathology of chronic atrophic gastritis model rats,and its mechanism of action may be related to the inhibition of TRAF6-mediated NLRP3 inflammatory vesicle activation.