小剂量多虑平对大鼠应激性胃黏膜损伤的治疗作用

目的:探讨小剂量多虑平(Doxepin)对大鼠应激性胃黏膜损伤(stress gastric mucosal damage,SGMD)的治疗作用,并就其可能机制初步研究。方法:采用浸水加束缚的方法制备大鼠应激性胃黏膜损伤模型。健康雄性SD大鼠50只,随机分为5组:假手术组(Sham组)、应激性胃黏膜损伤组(SGMD组)、溶剂对照组(Vehicle组)、多虑平预处理组(Doxepin组)、多虑平联合PI3K特异抑制剂LY294002组(Doxepin+LY组)。记录各组大鼠胃黏膜损伤指数。测算大鼠胃黏膜组织中丙二醛(malonalldehyde,MDA)含量、超氧化物歧化酶(superoxidedismutase,SOD)活性。Western blot法检测胃黏膜组织淋巴瘤/白血病-2(B cell lymphoma/leukemia-2,Bcl-2),Bcl-2相关X蛋白(Bcl-2 associated X protein,Bax),磷酸化Akt1(phosphorylated Akt1,p-Akt1)以及肿瘤坏死因子α(tumor necrosis factorα,TNF-α)蛋白的表达。结果:成功制备大鼠应激性胃黏膜损伤SGMD模型。与大鼠应激性胃黏膜损伤组相比,多虑平组大鼠胃黏膜损伤指数降低,胃黏膜组织MDA含量降低,SOD活性增强,p-Akt1的蛋白表达水平增强,且Bcl-2蛋白表达增强,Bax蛋白表达减弱(P<0.05)。而LY294002可削弱多虑平的以上作用(P<0.05)。结论:小剂量多虑平对大鼠应激性胃黏膜损伤具有保护作用,这种保护作用可能与其上调PI3K/Akt信号通路活性,上调Bcl-2蛋白表达,下调Bax蛋白表达活性作用密切相关。

Protective Effect of Doxepin on Stress Gastric Mucosal Damage in Rats

Objective:To observe the protective effect of doxepin of stress gastric mucosal damage(SGMD)in rats and to investigate the possible mechanisms.Methods:A total of 50 SD healthy male rats were randomly and equally divided into five groups:Sham group,SGMD group,Vehicle group,doxepin group,and doxepin+LY294002 group.Stress gastric mucosal damage model was induced by water immersion and restraint stress in water temperature(20±1)℃.The gastric mucosal injury index was recorded.The MDA concentration,SOD activity.Subsequently,the expression of Bcl-2,Bax and p-Akt1 was examined by western blotting.Results:The SGMD rat model was successfully established.The results showed that compared with SGMD group,doxepin remarkably reduced the gastric mucosal injury index and the gastric mucosal MDA contents,enhanced the activities of SOD,increase the level of phosphorylation of Akt1 and Bcl-2 expression,and decrease the level of Bax expression(P<0.05),but LY294002 reduced the above effects of doxepin(P<0.05).Conclusions:Low dose of doxepin has a protective effect on stress gastric mucosal damage in rats,which may be related to enhancing the activity of PI3K/Akt signaling pathway,raising the expression of Bcl-2 protein and reducing the expression of Bax protein.