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1.河南中医药大学第一附属医院脾胃肝胆科,郑州 450003
2.河南中医药大学第一附属医院消化内镜中心,郑州 450003
Received:02 February 2024,
Revised:2024-03-02,
Accepted:15 May 2024,
Published:30 August 2024
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张然,杨坤,曾震军,等.党参多糖对慢性萎缩性胃炎大鼠胃黏膜损伤的影响 [J].中国药房,2024,35(16):1985-1990.
ZHANG Ran,YANG Kun,ZENG Zhenjun,et al.Effects of Codonopsis pilosula polysaccharide on gastric mucosal injury in rats with chronic atrophic gastritis[J].ZHONGGUO YAOFANG,2024,35(16):1985-1990.
张然,杨坤,曾震军,等.党参多糖对慢性萎缩性胃炎大鼠胃黏膜损伤的影响 [J].中国药房,2024,35(16):1985-1990. DOI: 10.6039/j.issn.1001-0408.2024.16.08.
ZHANG Ran,YANG Kun,ZENG Zhenjun,et al.Effects of Codonopsis pilosula polysaccharide on gastric mucosal injury in rats with chronic atrophic gastritis[J].ZHONGGUO YAOFANG,2024,35(16):1985-1990. DOI: 10.6039/j.issn.1001-0408.2024.16.08.
目的
2
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
2
将大鼠随机分为对照组,模型组,CPP低、中、高剂量组(CPP 10、20、40 mg/kg)及ML385组(Nrf2抑制剂ML385 30 mg/kg联用CPP 40 mg/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;Western blot法检测胃黏膜组织Nrf2、HO-1、Bax、Bcl-2蛋白表达。
结果
2
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
2
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。
OBJECTIVE
2
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
2
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
2
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
2
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.
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