Xie Shan-Shan, Zhi Yong, Shao Chang-Ming, Zeng Bin-Fang
Department of Traditional Chinese Medicine, Xinjiang Medical University, Urumqi 830017, Xinjiang Uygur Autonomous Region, China.
World J Gastrointest Surg. 2024 Jul 27;16(7):2296-2307. doi: 10.4240/wjgs.v16.i7.2296.
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.
To investigate the therapeutic effects of YYHWM and its underlying mechanisms in a CAG rat model.
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.
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 38.52 ± 1.71, 23.06 ± 0.96 11.06 ± 0.70, and 493.09 ± 12.17 225.52 ± 17.44, < 0.01 for all), whereas those of IL-1β, IL-6, and TNF-α were significantly increased (30.15 ± 3.07 80.98 ± 4.47, 69.05 ± 12.72 110.85 ± 6.68, and 209.24 ± 11.62 313.37 ± 36.77, < 0.01 for all), and the protein levels of IL-10, JAK1, and STAT3 were higher in gastric mucosal tissues (0.47 ± 0.10 1.11 ± 0.09, 0.49 ± 0.05 0.99 ± 0.07, and 0.24 ± 0.05 1.04 ± 0.14, < 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 50.41 ± 3.53, 11.06 ± 0.70 15.33 ± 1.24, and 225.52 ± 17.44 329.22 ± 29.11, < 0.01 for all), decreased the levels of IL-1β, IL-6, and TNF-α (80.98 ± 4.47 61.56 ± 4.02, 110.85 ± 6.68 89.20 ± 8.48, and 313.37 ± 36.77 267.30 ± 9.31, < 0.01 for all), and evidently decreased the protein levels of IL-10 and STAT3 in gastric mucosal tissues (1.11 ± 0.09 0.19 ± 0.07 and 1.04 ± 0.14 0.55 ± 0.09, < 0.01 for both).
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.
中药养阴和胃合剂（YYHWM）在慢性萎缩性胃炎（CAG）治疗中显示出良好的临床疗效，但其作用机制尚不清楚。
研究YYHWM对CAG大鼠模型的治疗作用及其潜在机制。
将Sprague-Dawley大鼠分为对照组、模型组、维酶素组以及低、中、高剂量YYHWM组。采用N-甲基-N'-硝基-N-亚硝基胍、盐酸雷尼替丁、饥饱失常及乙醇灌胃诱导大鼠CAG。经过8周的干预期后，采集胃组织样本，进行染色，并检查组织病理学变化。采用酶联免疫吸附测定（ELISA）法检测血清中胃蛋白酶原I（PG-I）、胃蛋白酶原II（PG-II）、胃泌素-17（G-17）、白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）水平。采用蛋白质印迹法检测胃黏膜组织中白细胞介素-10（IL-10）、Janus激酶1（JAK1）和信号转导子和转录激活子3（STAT3）的蛋白表达。
模型组出现胃黏膜层破坏和炎性细胞浸润。与空白对照组相比, 模型组血清PGI、PGII和G-17水平显著降低（82.41±3.53比38.52±1.71、23.06±0.96比11.06±0.70、493.09±12.17比225.52±17.44，均P<0.01），而IL-1β、IL-6和TNF-α水平显著升高（30.15±3.07比80.98±4.47、69.05±12.72比110.85±6.68、209.24±11.62比313.37±36.77，均P<0.01），胃黏膜组织中IL-１０、JAK1和STAT3蛋白水平升高（0.47±0.10比1.11±0.0９、0.49±0.05比0.99±0.07、0.24±0.05比1.04±0.14，均P<0.01）。与模型组比较，高剂量YYHWM治疗显著改善胃黏膜组织损伤，提高PGI、PGII和G-17水平（38.52±1.71比50.41±3.53、11.06±0.70比15.33±1.24、225.52±17.44比329.22±29.11，均P<0.01），降低IL-1β、IL-6和TNF-α水平（80.98±4.47比61.56±4.02、110.85±6.68比89.20±8.48、313.37±36.77比267.30±9.31，均P<0.01），并明显降低胃黏膜组织中IL-10和STAT3蛋白水平（１.11±0.09比0.19±0.07、1.04±0.14比0.55±0.09，均P<0.01）；
YYHWM通过抑制IL-10/JAK1/STAT3信号通路，减少炎性因子释放，减轻胃黏膜损伤，增强胃分泌功能，从而改善CAG进展及癌变。
