葛根素调控MMP-2/TIMP-3对大鼠应激性胃溃疡的保护作用研究OA
Protective Effects of Puerarin Regulating MMP-2/TIMP-3 on Stress-Induced Gastric Ulcer in Rats
目的:探讨葛根素调控金属蛋白酶-2(MMP-2)/金属蛋白酶组织抑制因子-3(TIMP-3)通路对应激性胃溃疡(stress-induced gastric ulcers,SGU)大鼠的保护作用.方法:将40只SD大鼠分为对照组、模型组、葛根素低剂量组(50mg/kg)、葛根素高剂量组(100mg/kg),每组各10只.葛根素低、高剂量组给予葛根素溶液腹腔注射给药,连续7d,对照组和模型组给予等量生理盐水,采用浸水-束缚应激法建立大鼠应激性溃疡模型.观察记录大鼠胃运动、胃黏膜血流量(GMBF)、胃黏膜损伤程度、胃黏膜组织病理学变化,同时检测大鼠胃组织炎性细胞因子[白细胞介素(IL)-6、IL-1β、肿瘤坏死因子-α(TNF-α)、血清前列腺素E2(PGE2)]水平、氧化应激因子[超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)]水平以及MMP-2、TIMP-3表达量.结果:与对照组比较,模型组胃溃疡面积、胃黏膜溃疡指数(UI)、胃运动各项指标、IL-6、TNF-α、IL-1β、PGE2、MDA、MMP-2水平均显著升高(P＜0.05);GMBF、GSH-Px、SOD、TIMP-3水平显著下降(P＜0.05).与模型组比较,葛根素治疗组的大鼠胃溃疡面积、溃疡指数、胃运动各项指标、IL-6、TNF-α、IL-1β、PGE2、MDA、MMP-2 均显著降低(P＜0.05);GMBF、GSH-Px、SOD、TIMP-3 均显著升高(P＜0.05).与对照组比较,模型组大鼠胃组织的黏膜糜烂、血管扩张,可见广泛水肿和炎症细胞浸润.与模型组比较,葛根素治疗组大鼠胃组织黏膜病变严重程度明显缓解,水肿减轻,炎症细胞浸润到黏膜下层减少.结论:葛根素通过调控MMP-2/TIMP-3对SGU大鼠有显著的保护作用,其抑制应激性大鼠胃黏膜组织的炎症反应和氧化应激损伤,改善胃黏膜的微循环状态,从而减轻应激引起的胃黏膜损伤.
Objective:To investigate the protective effects of puerarin on stress-induced gastric ulcer(SGU)in rats by regulating MMP-2/TIMP-3 pathway.Methods:40 SD rats were divided into control group,model group,puerarin low-dose group(50 mg/kg),puerarin high-dose group(100 mg/kg),10 rats in each group.Puerarin low-dose and high-dose groups were given puerarin solution by intraperitoneal injection for 7 days.The control group and model group were given the same volume of normal saline.The stress ulcer model was established by immersion restraint stress method.The gastric motility,gastric mucosal blood flow(GMBF),the degree of gastric mucosal injury and pathological changes of gastric mucosa were observed and recorded.The levels of inflammatory cytokines[interleukin-6(IL-6),interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),serum prostaglandin E2(PGE2)]and oxidative stress factors[superoxide dismutase(SOD),malondialdehyde(MDA),glutathione peroxidase(GSH-Px)]and the expressions of MMP-2 and TIMP-3 in gastric tissue were detected.Results:Compared with the control group,the gastric ulcer area,gas-tric ulcer index(UI),gastric motility indexes,IL-6,TNF-α,IL-1β,PGE2,MDA,MMP-2 levels in the model group were significantly increased(P＜0.05);the levels of GMBF,GSH-Px,SOD and TIMP-3 de-creased significantly(P＜0.05).Compared with the model group,the gastric ulcer area,ulcer index,gastric motility indicators,as well as the levels of IL-6,TNF-α,IL-1β,PGE2,MDA and MMP-2 were signifi-cantly decreased in the puerarin treatment group(P＜0.05);GMBF,GSH-Px,SOD and TIMP-3 were signifi-cantly increased(P＜0.05).Compared with the control group,gastric mucosal erosion,vasodilation,extensive edema and inflammatory cell infiltration were observed in the model group.Compared with the model group,the severity of gastric mucosal lesions,edema and infiltration of inflammatory cells into the submucosa in the Puerarin Treatment group were significantly alleviated.Conclusion:Puerarin has a significant protective ef-fect on SGU in rats by regulating MMP-2/TIMP-3,which can inhibit the inflammatory reaction and oxida-tive stress injury of gastric mucosa in stress-induced rats,improve the microcirculation of gastric mucosa,and reduce the stress-induced gastric mucosal injury.
刘梦月;刘庆生
浙江中医药大学研究生院 浙江 杭州 310053杭州市中医院 浙江 杭州 310007
葛根素应激性胃溃疡MMP-2/TIMP-3胃黏膜损伤大鼠
puerarinstress-induced gastric lcerMMP-2/TIMP-3gastric mucosal injuryrats
《浙江中医杂志》 2026 (8)
664-668,5
浙江省医药卫生科技计划项目(2024KY182)
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