益气化瘀阻萎方通过调控PI3K/AKT信号通路缓解慢性萎缩性胃炎的实验研究

Experimental Study on the Alleviation of Chronic Atrophic Gastritis through Modulation of PI3K/AKT Signaling Pathway by Yiqi Huayu Zuwei Formula

[目的]探讨益气化瘀阻萎方对慢性萎缩性胃炎(chronic atrophic gastritis,CAG)模型小鼠的作用及其可能的机制。[方法]将昆明小鼠随机分为空白对照组,模型组,益气化瘀阻萎方低、高剂量组,通过2%水杨酸钠溶液灌胃结合游泳的方法复制CAG模型,建模成功后,益气化瘀阻萎方低、高剂量组给予益气化瘀阻萎方溶液灌胃治疗,空白对照组和模型组灌胃等量0.9%氯化钠溶液。4周后取材,苏木素-伊红(hematoxylin-eosin,HE)染色观察小鼠胃组织病理学变化,酶联免疫吸附试验(enzyme-linked immunosorbent assay,ELISA)检测血清中胃蛋白酶原Ⅰ(pepsinogen Ⅰ,PG Ⅰ)、PGⅡ水平及PGⅠ/PGⅡ的变化,免疫印迹试验检测胃组织中磷脂酰肌醇3-激酶/蛋白激酶B(phosphatidylinositol 3-kinase/protein kinase B,PI3K/AKT)信号通路蛋白表达水平。[结果]与模型组比较,益气化瘀阻萎方低、高剂量组小鼠胃组织结构紧密,黏膜层增厚,且给药组小鼠血清中PG Ⅰ、PG Ⅱ水平及PG Ⅰ/PG Ⅱ显著增高(P<0.01);给药组小鼠胃组织中PI3K、AKT、磷酸化-AKT(phospho-AKT,p-AKT)蛋白表达水平均显著降低(P<0.05,P<0.01)。[结论]益气化瘀阻萎方对CAG小鼠胃黏膜组织具有保护作用,其机制可能与抑制PI3K/AKT信号通路活化有关。

[Objective] To detect the effect of Yiqi Huayu Zuwei Formula on chronic atrophic gastritis(CAG) model mice and to investigate the potential mechanism. [Methods] Kunming mice were randomly divided into blank control group,model group,Yiqi Huayu Zuwei Formula low-dose group and Yiqi Huayu Zuwei Formula high-dose group,and CAG model was replicated by gavage with 2% sodium salicylate solution combined with swimming. After successful modeling,Yiqi Huayu Zhiwei Formula low and high dose groups were given Yiqi Huayu Zhiwei Formula solution by gavage. Blank control group and model group were treated with equal amount of 0.9% sodium chloride solution by gavage,and the histopathological changes in the stomach of mice were observed after four weeks. Enzyme-linked immunosorbent assay(ELISA) was used to detect the changes of serum pepsinogen Ⅰ(PG Ⅰ),PG Ⅱ and PG Ⅰ/PG Ⅱ;Western blot was used to detect the protein expression level of phosphatidylinositol 3-kinase/protein kinase B(PI3K/AKT) signaling pathway in gastric tissue.[Results] Compared with model group,the gastric tissues of mice in Yiqi Huayu Zuwei Formula low-dose and high-dose groups had compact structure and thickened mucosal layer,and the levels of PG Ⅰ,PG Ⅱ and PG Ⅰ/PG Ⅱ in the serum of mice in administered groups were significantly higher than those in model group(P<0.01). The protein expression of PI3K,AKT and phospho-AKT(p-AKT) in gastric tissues of mice in administrated groups were significantly reduced(P<0.05,P<0.01). [Conclusion] The mechanism of the protective effect of Yiqi Huayu Zuwei Formula on gastric mucosal tissues of CAG mice may be made through the inhibition of the PI3K/AKT signaling pathway.