热休克蛋白70对内毒素致门静脉高压性胃病大鼠胃黏膜损伤的保护作用研究

Protective role of heat-shock protein 70 in gastric mucosal lesion induced by endotoxin in cirrhotic rats with portal hypertensive gastropathy

目的:探讨热休克蛋白70(HSP70)对内毒素诱导的肝硬化门静脉高压性胃病(PHG)大鼠胃黏膜损伤的作用及机制。方法:以CCl4制备肝硬化PHG大鼠模型。热处理诱导HSP70表达,注射内毒素及其拮抗剂BPI21,酶联免疫吸附测定(ELISA)检测HSP70和TNF-α水平,HE染色观察胃黏膜病理变化。实验分为正常对照组、PHG组、PHG+热处理组、PHG+内毒素组及PHG+BPI21组。结果:(1)PHG时胃黏膜HSP70表达明显减少,血浆内毒素及胃黏膜TNF-α表达明显增加,胃黏膜损伤明显;(2)外源性内毒素增加PHG大鼠胃黏膜TNF-α表达,加重其胃黏膜损伤;BPI21则显著减少其TNF-α表达,减轻胃黏膜损伤;(3)热处理增加PHG大鼠胃黏膜HSP70表达,减少TNF-α表达,减轻胃黏膜损伤。结论:HSP70减轻PHG胃黏膜损伤,其机制可能与降低胃黏膜TNF-α水平有关。

AIM： To investigate the protective role of heat-shock protein 70（HSP70） in the pathogenesis of gastric mucosal damage in cirrhotic rats with portal hypertensive gastropathy（PHG）.METHODS： The rat model of liver cirrhosis with PHG was established by injection with tetrachloride.The animals were divided into normal control group,PHG group,PHG＋heat treatment group,PHG＋BPI21 group and PHG＋endotoxin groups.The endotoxin used in the experiment was at the dose of 3 mg/kg and endotoxin antagonist BPI21 was at the dose of 2 mg/kg.HSP70 was induced by pre-treating the animals with mild whole-body heating.The levels of HSP70 and tumor necrosis factor alpha（TNF-α） in the gastric mucosa were measured by ELISA.Furthermore,the pathological changes of the gastric mucosa were observed under microscope with HE staining.RESULTS： Compared with the normal control rats,the rats in PHG group showed obvious gastric pathological lesion,decrease in HSP70 production and increase in TNF-α level in the gastric mucosa,and increased endotoxin concentration in the plasma.Compared with PHG＋endotoxin group,the gastric mucosal lesion in PHG＋BPI21 group was significantly attenuated,accompanied by the increase in HSP70 production and decrease in TNF-α level in the gastric mucosa.Heat treatment increased HSP70 production and decreased TNF-α concentration in the PHG rats,thus attenuating the gastric mucosal damage.CONCLUSION： HSP70 alleviates the gastric mucosal lesion induced by endotoxin in cirrhotic rats with PHG and decreases the concentration of TNF-α in gastric mucosa,indicating a protective role of HSP70 in the pathogenesis of gastric mucosal damage in PHG.