背景:中药养阴活味合剂(YYHWM)治疗慢性萎缩性胃炎(CAG)具有良好的临床疗效,但其活动的潜在机制仍不清楚。
目的:研究YYHWM在CAG大鼠模型中的治疗作用及其机制。
方法:将Sprague-Dawley大鼠分为对照组,模型,维生素A酶,低,中等,和高剂量YYHWM组。使用N-甲基-N'-硝基-N-亚硝基胍在大鼠中诱导CAG,盐酸雷尼替丁,饥饿和饱腹感扰动,和乙醇灌胃。经过8周的干预期,采集了胃样本,染色,并检查组织病理学变化。ELISA用于定量血清PG-I的水平,PG-II,G-17,IL-1β,IL-6和TNF-α。进行蛋白质印迹分析以评估IL-10、JAK1和STAT3的蛋白表达。
结果:模型组胃粘膜层破裂,炎性细胞浸润。与空白对照组相比,PGI的血清水平,PGII,模型组G-17明显减少(82.41±3.53vs38.52±1.71,23.06±0.96vs11.06±0.70,493.09±12.17vs225.52±17.44,P<0.01),而IL-1β,IL-6和TNF-α显着增加(30.15±3.07vs80.98±4.47,69.05±12.72vs110.85±6.68和209.24±11.62vs313.37±36.77,P<0.01),胃粘膜组织中IL-10,JAK1和STAT3的蛋白水平较高(0.47±0.10vs1.11±0.09,0.49±0.05vs0.99±0.07和0.24±0.05vs1.04±0.14,P<0.01)。与模型组相比,大剂量YYHWM治疗显著改善胃粘膜组织损伤,增加了PGI的水平,PGII,和G-17(38.52±1.71vs50.41±3.53,11.06±0.70vs15.33±1.24和225.52±17.44vs329.22±29.11,全部P<0.01),降低IL-1β水平,IL-6和TNF-α(80.98±4.47vs61.56±4.02,110.85±6.68vs89.20±8.48和313.37±36.77vs267.30±9.31,全部P<0.01),并明显降低胃粘膜组织中IL-10和STAT3的蛋白水平(1.11±0.09vs0.19±0.07和1.04±0.14vs0.55±0.09,两者均P<0.01)。
结论:YYHWM通过抑制IL-10/JAK1/STAT3通路减少炎症因子的释放,减轻胃粘膜损伤,增强胃液分泌功能,从而改善CAG发展和癌症转化。
BACKGROUND: The Chinese medicine Yangyin Huowei mixture (YYHWM) exhibits good clinical efficacy in the treatment of chronic atrophic gastritis (CAG), but the mechanisms underlying its activity remain unclear.
OBJECTIVE: To investigate the therapeutic effects of YYHWM and its underlying mechanisms in a CAG rat model.
METHODS: Sprague-Dawley rats were allocated into control, model, vitacoenzyme, and low, medium, and high-dose YYHWM groups. CAG was induced in rats using N-methyl-N\'-nitro-N-nitrosoguanidine, ranitidine hydrochloride, hunger and satiety perturbation, and ethanol gavage. Following an 8-wk intervention period, stomach samples were taken, stained, and examined for histopathological changes. ELISA was utilized to quantify serum levels of PG-I, PG-II, G-17, IL-1β, IL-6, and TNF-α. Western blot analysis was performed to evaluate protein expression of IL-10, JAK1, and STAT3.
RESULTS: The model group showed gastric mucosal layer disruption and inflammatory cell infiltration. Compared with the blank control group, serum levels of PGI, PGII, and G-17 in the model group were significantly reduced (82.41 ± 3.53 vs 38.52 ± 1.71, 23.06 ± 0.96 vs 11.06 ± 0.70, and 493.09 ± 12.17 vs 225.52 ± 17.44, P < 0.01 for all), whereas those of IL-1β, IL-6, and TNF-α were significantly increased (30.15 ± 3.07 vs 80.98 ± 4.47, 69.05 ± 12.72 vs 110.85 ± 6.68, and 209.24 ± 11.62 vs 313.37 ± 36.77, P < 0.01 for all), and the protein levels of IL-10, JAK1, and STAT3 were higher in gastric mucosal tissues (0.47 ± 0.10 vs 1.11 ± 0.09, 0.49 ± 0.05 vs 0.99 ± 0.07, and 0.24 ± 0.05 vs 1.04 ± 0.14, P < 0.01 for all). Compared with the model group, high-dose YYHWM treatment significantly improved the gastric mucosal tissue damage, increased the levels of PGI, PGII, and G-17 (38.52 ± 1.71 vs 50.41 ± 3.53, 11.06 ± 0.70 vs 15.33 ± 1.24, and 225.52 ± 17.44 vs 329.22 ± 29.11, P < 0.01 for all), decreased the levels of IL-1β, IL-6, and TNF-α (80.98 ± 4.47 vs 61.56 ± 4.02, 110.85 ± 6.68 vs 89.20 ± 8.48, and 313.37 ± 36.77 vs 267.30 ± 9.31, P < 0.01 for all), and evidently decreased the protein levels of IL-10 and STAT3 in gastric mucosal tissues (1.11 ± 0.09 vs 0.19 ± 0.07 and 1.04 ± 0.14 vs 0.55 ± 0.09, P < 0.01 for both).
CONCLUSIONS: YYHWM reduces the release of inflammatory factors by inhibiting the IL-10/JAK1/STAT3 pathway, alleviating gastric mucosal damage, and enhancing gastric secretory function, thereby ameliorating CAG development and cancer transformation.