香砂六君子汤对慢性萎缩性胃炎大鼠的治疗作用机制研究
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国家自然科学基金项目(82003946);河南省科技厅科技攻关项目(202102310408)


Effect of Xiangsha Liujunzi Decoction on Rats with Chronic Atrophic Gastritis
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    摘要:

    目的:探讨香砂六君子汤对慢性萎缩性胃炎(CAG)大鼠的治疗作用及其机制。方法:将72只SD大鼠简单随机化分为对照组(16只)、模型组(16只)、维酶素组(10只)、香砂六君子汤低剂量组(10只)、香砂六君子汤中剂量组(10只)、香砂六君子汤高剂量组(10只)。除对照组外,其余各组采用N-甲基-N'-硝基-N-亚硝基胍溶液联合饥饱失常饮食控制法制备CAG模型,连续造模16周。造模16周后,对照组、模型组给予生理盐水(10 mL/kg)灌胃,维酶素组给予维酶素溶液(50 mg/kg)灌胃,香砂六君子汤低、中、高剂量组分别给予6、12、24 g/kg,每天1次,连续8周。观察大鼠一般状况,取材后采用苏木精-伊红染色法观察胃组织病理学,酶联免疫吸附试验法检测血清胃动素(MTL)、胃泌素(Gas)、生长抑素(SS)以及胃组织中白细胞介素-6(IL-6)、IL-1β和肿瘤坏死因子-α(TNF-α),实时荧光定量聚合酶链式反应检测胃组织中转化生长因子β1(TGF-β1)/磷脂酰肌醇-3-激酶(PI3K)/蛋白激酶B(AKT)信号通路相关mRNA表达,蛋白质免疫印迹法检测胃组织TGF-β1、PI3K/p-PI3K和AKT/p-AKT蛋白表达。结果:与模型组比较,各观察组大鼠一般状况、胃黏膜腺体萎缩程度以及炎症细胞浸润程度得到不同程度的改善。与对照组比较,模型组大鼠血清MTL水平高,Gas、SS水平低(均P<0.01)。与模型组比较,维酶素组和香砂六君子汤组血清MTL水平低,Gas、SS水平高(均P<0.01)。与对照组比较,模型组大鼠胃组织中IL-6、IL-1β、TNF-α水平高(均P<0.01)。与模型组比较,维酶素组和香砂六君子汤组胃组织中IL-6、IL-1β、TNF-α水平低(均P<0.01)。与对照组比较,模型组大鼠胃组织中TGF-β1、PI3K、AKT mRNA表达高(均P<0.01)。与模型组比较,维酶素组和香砂六君子汤组胃组织中TGF-β1、PI3K、AKT mRNA表达低(均P<0.01)。与对照组比较,模型组大鼠胃组织中TGF-β1蛋白表达量及PI3K/p-PI3K、AKT/p-AKT高(均P<0.01);与模型组比较,维酶素组和香砂六君子汤组中TGF-β1蛋白表达量及PI3K/p-PI3K、AKT/p-AKT低(均P<0.01)。香砂六君子汤高剂量组以上指标变化最为明显。结论:香砂六君子汤可有效改善CAG大鼠症状,其机制可能与抑制TGF-β1/PI3K/AKT信号通路激活有关。

    Abstract:

    To investigate the effects of Xiangsha Liujunzi Decoction on treating rats with chronic atrophic gastritis(CAG) and the mechanism.Methods:A total of 72 SD rats were randomly divided into the control group(16 rats),model group(16 rats),vitacoenzyme group(10 rats),the groups with low dose,medium dose and high dose of Xiangsha Liujunzi Decoction,with 10 rats in each of the three groups.In addition to the control group,for the remaining groups,N-methyl-N'-nitro-N-nitrosoguanidine solution combined with the hunger and satiety disorder diet control method was employed to prepare the CAG model,with continuous modeling for 16 weeks.After 16 weeks of modeling,the control group and model group were given physiological saline(10 mL/kg) for gavage administration,the vitacoenzyme group was given vitacoenzyme solution(50 mg/kg) for administration,and the groups with low,medium,and high doses of Xiangsha Liujunzi Decoction were given 6,12,and 24 g/kg respectively,with the administration conducted once a day for eight consecutive weeks.The general condition of rats was observed,with the hematoxylin-eosin(HE) staining method adopted to observe the pathology of gastric tissue after sampling.Enzyme linked immunosorbent assay(ELISA) method was employed to detect serum motilin(MTL),gastrin(Gas),somatostatin(SS),as well as interleukin(IL)-6,IL-1β,and tumor necrosis factor-α(TNF-α) in gastric tissue.Real-time fluorescence quantitative PCR was utilized to detect the mRNA expression related to the transforming growth factor β1(TGF-β1)/phosphatidylin-ositol-3-kinase(PI3K)/protein kinase B(AKT) signaling pathway in gastric tissue.Western blotting was adopted to detect the protein expression of TGF-β1,PI3K/p-PI3K,and AKT/p-AKT in gastric tissue.Results:Compared with the model group,the general condition,atrophy degree of gastric mucosal glands,and infiltration degree of inflammatory cells of rats in each treatment group were improved to varying degrees.Compared with the control group,the serum MTL level of rats in the model group was high,while the Gas and SS levels were low(P<0.01).Compared with the model group,the serum MTL levels were low in the vitacoenzyme group and Xiangsha Liujunzi Decoction group,while the Gas and SS levels were high(P<0.01).Compared with the control group,the levels of IL-6,IL-1β,and TNF-α in the gastric tissue of the rats in the model group were high(P<0.01).Compared with the model group,the levels of IL-6,IL-1β,and TNF-α in gastric tissue were low in the rats of the vitacoenzyme group and Xiangsha Liujunzi Decoction group(P<0.01).Compared with the control group,the mRNA expression of TGF-β1,PI3K,and AKT in the gastric tissue of rats in the model group was high(P<0.01).Compared with the model group,the mRNA expression of TGF-β1,PI3K,and AKT in gastric tissue was low in the vitacoenzyme group and Xiangsha Liujunzi Decoction group(P<0.01).Compared with the control group,the expression levels of TGF-β1 protein,PI3K/p-PI3K,and AKT/p-AKT were high in the gastric tissue of rats in the model group(P<0.01).Compared with the model group,the expression levels of TGF-β1 protein,PI3K/p-PI3K,and AKT/p-AKT were low in the vitacoenzyme group and Xiangsha Liujunzi Decoction group(P<0.01).The changes in the above indicators were most significant in the group with high dose of Xiangsha Liujunzi Decoction.Conclusion:Xiangsha Liujunzi Decoction can effectively improve the symptoms of rats with CAG,and its mechanism may be related to the suppression of the TGF-β1/PI3K/AKT signaling pathway.

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闫欣,陈永祥,张秀芝.香砂六君子汤对慢性萎缩性胃炎大鼠的治疗作用机制研究[J].世界中医药,2025,(07).

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  • 收稿日期:2024-07-15
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  • 在线发布日期: 2025-06-11
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