党参多糖对慢性萎缩性胃炎大鼠胃黏膜损伤的影响
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篇名: 党参多糖对慢性萎缩性胃炎大鼠胃黏膜损伤的影响
TITLE: Effects of Codonopsis pilosula polysaccharide on gastric mucosal injury in rats with chronic atrophic gastritis
摘要: 目的 探究党参多糖(CPP)调节核转录因子红系2相关因子2(Nrf2)/血红素加氧酶1(HO-1)信号通路对慢性萎缩性胃炎(CAG)大鼠胃黏膜损伤的影响。方法将大鼠随机分为对照组,模型组,CPP低、中、高剂量组(CPP10、20、40mg/kg)及ML385组(Nrf2抑制剂ML38530mg/kg联用CPP40mg/kg),每组10只,采用N-甲基-N′-硝基-N-亚硝基胍联合不规律饮食法建立CAG大鼠模型后,连续给药6周。HE染色观察胃黏膜组织病理形态变化;检测血清胃泌素(GAS)、胃动素(MTL)、胃蛋白酶(PP)及胃黏膜组织肿瘤坏死因子α(TNF-α)、白细胞介素8(IL-8)、丙二醛(MDA)、超氧化物歧化酶(SOD)水平;TUNEL染色观察胃黏膜组织细胞凋亡情况;免疫组化法观察胃黏膜组织Nrf2、B淋巴细胞瘤-2(Bcl-2)相关X蛋白(Bax)表达;Westernblot法检测胃黏膜组织Nrf2、HO-1、Bax、Bcl-2蛋白表达。结果与对照组比较,模型组大鼠胃黏膜组织损伤;GAS、MTL、PP、SOD水平,Nrf2、HO-1、Bcl-2蛋白表达水平均显著降低(P<0.05);MDA、TNF-α、IL-8水平,细胞凋亡指数,Bax蛋白表达水平均显著升高(P<0.05)。与模型组比较,CPP低、中、高剂量组胃黏膜组织病理有不同程度改善;各定量指标均显著逆转(P<0.05);Nrf2抑制剂ML385可显著减弱高剂量CPP对CAG大鼠上述指标的改善作用(P<0.05)。结论CPP能改善CAG大鼠胃黏膜损伤,抑制氧化应激、炎症反应和细胞凋亡,其作用机制可能与激活Nrf2/HO-1信号通路有关。
ABSTRACT: OBJECTIVE To investigate the effects of Codonopsis pilosula polysaccharide (CPP) regulating the nuclear factor- erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway on gastric mucosal injury in rats with chronic atrophic gastritis (CAG). METHODS Rats were randomly divided into control group, model group, CPP low-dose, medium-dose and high-dose groups (CPP 10, 20, 40 mg/kg), and ML385 group (Nrf2 inhibitor ML385 30 mg/kg+CPP 40 mg/kg), 10 rats per group. CAG rat model was established using N-methyl-N′- nitro-N-nitrosoguanidine combined with irregular diet, then they were given drugs for consecutive 6 weeks. HE staining was used to observe the pathological changes in gastric tissue morphology; the levels of serum gastrin (GAS), motilin (MTL), pepsin (PP), as well as tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8) malondialdehyde (MDA) and superoxide dismutase (SOD) in gastric mucosal tissue were detected; TUNEL assay was used to observe gastric mucosal tissue cell apoptosis; immunohistochemical assay was adopted to observe the expressions of Nrf2 and recombinant Bcl2 associated X protein (Bax) in gastric mucosal tissue; Western blot was used to detect the expressions of Nrf2, HO-1, Bax and Bcl-2 proteins in gastric mucosal tissue. RESULTS Compared with the control group, the gastric mucosal tissue was damaged; the levels of GAS, MTL, PP and SOD, and the protein expressions of Nrf2, HO-1 and Bcl-2 were significantly reduced in model group (P<0.05), while the levels of MDA, TNF-α and IL-8, the cell apoptosis index, and the protein expression of Bax were significantly increased (P<0.05). Compared with model group, CPP low-dose, medium-dose and high- dose groups showed varying degrees of improvement in gastric mucosal histopathology; the levels of the quantitative indicators were significantly reversed (P<0.05). Nrf2 inhibitor ML385 significantly attenuated the improvement effect of high-dose CPP on the above indicators in CAG rats (P<0.05). CONCLUSIONS CPP can improve gastric mucosal injury in CAG rats, and inhibit oxidative stress, inflammatory response, and cell apoptosis. The mechanism of action may be related to the activation of Nrf2/HO-1 signaling pathway.
期刊: 2024年第35卷第16期
作者: 张然;杨坤;曾震军;李素娟;刘杰
AUTHORS: ZHANG Ran,YANG Kun,ZENG Zhenjun,LI Sujuan,LIU Jie
关键字: 党参多糖;慢性萎缩性胃炎;胃黏膜损伤;Nrf2/HO-1信号通路
KEYWORDS: Codonopsis pilosula polysaccharides; chronic
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