安胃汤对慢性萎缩性胃炎大鼠ULK1相关自噬蛋白表达的影响

Effect of Anwei Decoction(安胃汤)on Expression of ULK1-related Autophagy Protein in Rats with Chronic Atrophic Gastritis

目的探讨ULK1相关自噬蛋白在安胃汤治疗慢性萎缩性胃炎大鼠的机制。方法将72只SD大鼠随机分为6组,即正常对照组、模型对照组、实验观察安胃汤高剂量组(AH组)、实验观察安胃汤中剂量组(AM组)、实验观察安胃汤低剂量组(AL组)、阴性对照组。用氨水和脱氧胆酸钠溶液自由饮用,饥饱失常喂养,以建立慢性萎缩性胃炎模型。再给予不同浓度的安胃汤灌胃治疗4周后。观察大鼠胃组织病理变化和自噬相关基因与蛋白的表达变化。结果从病理结果来看,与阴性对照组比较,安胃汤各治疗组胃部腺体萎缩情况有不同程度减少,固有层内可见淋巴细胞、浆细胞、酸性细胞浸润减少;在透射电镜的检测结果中,正常对照组、模型对照组和阴性对照组未发现明显自噬或极少,而各安胃汤治疗组中均发现了有不同数量的自噬溶酶体的存在。安胃汤各治疗组中ULK1、Atg13、beclin-1、LC3 mRNA的表达均有明显上调(P<0.05);安胃汤各治疗组中ULK1、Atg13、beclin-1、LC3蛋白的表达亦有上调(P<0.05);结论安胃汤在改善慢性萎缩性胃炎的同时能够上调组织中ULK1、Atg13、beclin-1和LC3蛋白的相对表达,可认为安胃汤的治疗机制与自噬相关。

Objective To investigate the mechanism of ULK1-related autophagy protein in the treatment of chronic atrophic gastritis(CAG)rats with Anwei Decoction(安胃汤).Methods Seventy-two SD rats were randomly divided into 6 groups:normal control group,model control group,AH group(Anwei Decoction high-dose group),AM group(Anwei Decoction medium-dose group),AL group(Anwei Decoction low-dose group)and negative control group.The model of chronic atrophic gastritis was established by free drinking with ammonia and sodium deoxycholate solution and feeding with hunger disorder.Then different concentrations of Anwei Decoction were given to the corresponding groups intragastrically after 4 weeks.The pathological changes of gastric tissues and the expressions of autophagy-related genes and proteins in rats were observed.Results The pathological results showed that compared with those in the negative control group,the gastric gland atrophy in Anwei Decoction groups was decreased to different degrees,and the infiltration of lymphocytes,plasma cells and acid cells in the lamina propria decreased.In real-time PCR detection,the expressions of ULK1,Atg13,beclin-1 and LC3 mRNA in each treatment group of Anwei Decoction were significantly up-regulated(P<0.05).Western blot showed that ULK1,Atg13,beclin-1 and LC3 proteins were also up-regulated in Anwei Decoction treatment groups(P<0.05).Finally,in the transmission electron microscope test results,no significant autophagy or minimal autophagy was found in the normal control group,model control group and negative control group,while different amounts of autophagy lysosomes were found in each Anwei Decoction treatment groups.Conclusion Anwei Decoction can improve the relative expressions of ULK1,Atg13,beclin-1 and LC3 proteins in tissues while improving chronic atrophic gastritis,suggesting that the therapeutic mechanism of Anwei Decoction is related to autophagy.