基于NLRP3/Caspase-1/GSDMD信号通路探讨清化饮对慢性萎缩性胃炎大鼠胃上皮细胞焦亡的影响  

Exploring the Effect of Qinghua Decoction on the Scorching of Gastric Epithelial Cells in Rats with Chronic Atrophic Gastritis Based on NLRP3/Caspase-1/GSDMD Signaling Pathway

作　　者：林翔英 王鑫[1] 钟国栋[1] 黄铭涵[1] 林建龙[1] LIN Xiangying;WANG Xin;ZHONG Guodong;HUANG Minghan;LIN Jianlong(The Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine,Fuzhou 350003,Fujian,China)

机构地区：[1]福建中医药大学附属第二人民医院,福建福州350003

出　　处：《实用中医内科杂志》2024年第11期32-35,I0016,I0028,共6页Journal of Practical Traditional Chinese Internal Medicine

基　　金：国家自然科学基金项目(82174365);福建省自然科学基金项目(2020J01253)。

摘　　要：目的观察清化饮对慢性萎缩性胃炎(chronic atrophic gastritis,CAG)大鼠胃上皮NOD样受体蛋白3(NLRP3)/胱天蛋白酶-1(Caspase-1)/消皮素D(GSDMD)细胞焦亡通路的影响,探讨清化饮治疗CAG的可能机制。方法随机将大鼠分为空白对照组(n=8)及造模组(n=28),采用“氨水+去氧胆酸钠+乙醇法灌胃+高脂高糖饮食+人工气候箱饲养”复合法建立病证结合CAG大鼠模型,造模成功后将其随机分为模型组、维酶素治疗组和清化饮治疗组(n=8)。采用HE染色观察大鼠胃黏膜病变情况,Real-time PCR法检测胃组织NLRP3、Caspase-1、β-catenin、GSDMD mRNA表达情况,ELISA法检测血清IL-1β、IL-6、IL-18水平。结果与空白对照组相比,模型组大鼠炎症细胞浸润明显,胃黏膜固有腺体萎缩,胃黏膜组织中NLRP3、Caspase-1、β-catenin mRNA表达水平显著升高(P<0.01),GSDMD mRNA表达水平显著降低(P<0.01);血清IL-1β、IL-6、IL-18含量显著上升(P<0.01)。与模型组比较,清化饮治疗组胃黏膜固有腺体萎缩情况及炎症程度明显改善,NLRP3、Caspase-1、β-catenin mRNA表达蛋白表达水平均显著下降(P<0.01),GSDMD mRNA表达水平上升(P<0.01);血清IL-1β、IL-6、IL-18含量显著下降(P<0.01)。结论清化饮可有效改善CAG大鼠胃黏膜组织病理改变,其机制可能与调控NLRP3/Caspase-1/GSDMD信号通路,抑制细胞焦亡,从而降低胃黏膜炎症水平有关。Objective To observe the effect of Qinghua Decoction(QHD)on the pyroptosis of gastric epithelial NOD-like receptor protein 3(NLRP3)/cysteine protease-1(Caspase-1)/gasdermin D(GSDMD)in rats with chronic atrophic gastritis(CAG),and to explore the possible mechanism of QHΥin the treatment of CAG.Method Rats were randomLy divided into a blank control group(n=8)and a modeling group(n=28).A combination of ammonia+sodium deoxycholate+ethanol gavage+high-fat and high-sugar diet+artificial climate chamber was used to establish a CAG rat model combined with disease and TCM syndrome.After successful modeling,the models were randomLy divided into the model group,the vincristine treatment group,and the QHD treatment group(n=8).The gastric mucosa lesions were observed by HE staining.The expression of NLRP3,Caspase-1,β-catenin,and GSDMD mRNA were detected by Real-time PCR.The levels of serum IL-1β,IL-6,and IL-18 were detected by ELISA.Results Compared with the blank control group,the inflammatory cell infiltration and atrophy of intrinsic glands in the gastric mucosa of the model rats were obvious;NLRP3,Caspase-1,andβ-catenin mRNA expression levels in the gastric mucosa tissues were significantly increased(P<0.01);GSDMD mRNA expression levels were significantly decreased(P<0.01);IL-1β,IL-6 and IL-18 levels in serum were significantly increased(P<0.01).Compared with the model group,the atrophy of intrinsic glands of gastric mucosa and the degree of inflammation in the QHD treatment group were significantly improved,and the expression levels of NLRP3,Caspase-1,andβ-catenin mRNA were significantly decreased(P<0.01).GSDMD mRNA expression level was increased(P<0.01).The levels of serum IL-1β,IL-6,and IL-18 decreased significantly(P<0.01).Conclusion QHD can effectively improve the histopathological changes of gastric mucosa in CAG rats.Its mechanism may be related to the regulation of the NLRP3/Caspase-1/GSDMD signaling pathway,inhibition of pyroptosis,and reduction of gastric mucosal inflammation level.

关 键 词：清化饮 细胞焦亡 慢性萎缩性胃炎 NOD样受体蛋白3 胱天蛋白酶-1 消皮素D 

分 类 号：R256.3[医药卫生—中医内科学]