机构地区:[1]湖南中医药大学,湖南长沙410208 [2]湖南中医药大学第一附属医院,湖南长沙410007
出 处:《现代中西医结合杂志》2023年第20期2798-2802,2816,共6页Modern Journal of Integrated Traditional Chinese and Western Medicine
基 金:湖南省教育厅科学研究重点项目(20A371)。
摘 要:目的基于肌醇需求酶1α(IRE1α)信号通路探讨肝胃百合汤对吲哚美辛所致胃溃疡大鼠胃黏膜的保护作用及机制。方法将36只SD大鼠随机分为空白组、模型组、奥美拉唑组、肝胃百合汤组,每组9只。肝胃百合汤组和奥美拉唑组分别给予7.29 g/(kg·d)肝胃百合汤和3.6 mg/(kg·d)奥美拉唑灌胃,空白组和模型组给予等量蒸馏水灌胃,连续灌胃1周后,模型组、奥美拉唑组、肝胃百合汤组给予80 mg/kg吲哚美辛灌胃诱导胃溃疡,造模3 h后处死大鼠,观察并计算胃溃疡指数,HE和TUNEL染色观察胃黏膜损伤及胃组织细胞凋亡情况,Western blot法检测胃组织内质网应激相关蛋白[葡萄糖调节蛋白78(GRP78)、IRE1α、磷酸化肌醇需求酶1α(p-IRE1α)、凋亡信号激酶1(ASK1)、胱天蛋白酶12(Caspase-12)]表达情况。结果与空白组比较,模型组大鼠胃黏膜出现严重缺损,腺体结构紊乱,大量细胞死亡和炎性细胞浸润,胃组织细胞凋亡明显,胃组织中GRP78、p-IRE1α/IRE1α、ASK1、Caspase-12蛋白相对表达量均明显升高(P均<0.05);与模型组比较,肝胃百合汤组和奥美拉唑组大鼠胃黏膜损伤明显减轻,胃溃疡指数均明显降低(P均<0.05),凋亡细胞明显减少,胃组织中GRP78、p-IRE1α/IRE1α、ASK1、Caspase-12蛋白相对表达量均明显降低(P均<0.05)。结论肝胃百合汤可能通过抑制IRE1α信号通路介导的内质网应激,减轻胃黏膜细胞凋亡,从而发挥胃黏膜保护作用。Objective It is to explore the protective effect and mechanism of Liver and Stomach Lily Decoction on gastric mucosa of rats with indomethacin-induced gastric ulcer based on inositol-requiring enzyme 1α(IRE1α)signaling pathway.Methods Thirty-six SD rats were randomly divided into blank group,model group,omeprazole group and Liver and Stomach Lily Decoction group,with 9 rats in each group.The Liver and Stomach Lily Decoction group and omeprazole group were given 7.29 g/(kg·d)Liver and Stomach Lily Decoction and 3.6 mg/(kg·d)omeprazole by gavage,respectively,and the blank and model groups were given an equal amount of distilled water by gavage,and after 1 week of consecutive gavage,the model group,omeprazole group,and Liver and Stomach Lily Decoction group were given 80 mg/kg indomethacin by gavage to induce gastric ulcer.The rats were executed at 3 h after modeling,and the gastric ulcer index was observed and calculated,the gastric mucosal damage and apoptosis of gastric tissues were observed by HE and TUNEL staining,and the expressions of endoplasmic reticulum stress-related proteins[glucose-regulated protein 78(GRP78),IRE1α,phosphatidylinositol-requiring enzyme 1α(p-IRE1α),apoptosis signaling kinase 1(ASK1),and Caspase-12]in gastric tissues were detected by Western blot method.Results Compared with the blank group,the gastric mucosa of rats in the model group showed severe defects,disordered of glandular structure,a large number of cell death and inflammatory cell infiltration,obvious apoptosis of gastric tissues,and the relative expressions of GRP78,p-IRE1α/IRE1α,ASK1,and Caspase-12 proteins in gastric tissues were all significantly increased(all P<0.05);compared with the model group,the gastric mucosa damage of rats in the Liver and Stomach Lily Decoction group and omeprazole group was significantly relieved,the gastric ulcer indexes were significantly reduced(both P<0.05),the apoptotic cells were significantly reduced,and the relative expressions of GRP78,p-IRE1α/IRE1α,ASK1,and Caspase-12 proteins
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