3-甲基腺嘌呤对急进高原缺氧大鼠肠上皮细胞损伤的自噬影响研究

目的探讨自噬抑制剂3-甲基腺嘌呤(3-MA)对急进高原缺氧大鼠肠上皮细胞自噬水平及损伤程度的影响。方法将50只Wistar大鼠随机分成5组(A~E组),在低氧氧舱环境下建立急进高原缺氧大鼠肠上皮细胞损伤模型,用3-MA进行处理,肉眼观察各组大鼠的行为学改变,HE染色分析大鼠肠组织的损伤程度,免疫组织化学检测自噬相关蛋白LC-3、Beclin-1的表达情况,RT-PCR方法检测LC-3、Beclin-1 mRNA的表达情况。结果 3-MA作用于缺氧大鼠肠上皮细胞后,肠组织的病理性损伤明显加重,自噬相关蛋白LC-3、Beclin-1及其相关mRNA表达也显著降低,细胞自噬水平下降。结论 3-MA可能通过降低细胞自噬水平加重急进高原缺氧肠上皮细胞损伤,细胞自噬可能是急进高原缺氧肠上皮细胞损伤过程中的重要保护因素之一。

Study on the influence of 3-Methyladenine on autophagy in intestinal epithelial cells of hypoxic rats rapidly ascending to high altitude areas

Objective To investigate the influence of autophagy inhibitor 3-Methyladenine (3-MA) on the level of autophagy and the injury extent of intestinal epithelial cells caused by hypobaric hypoxia in rats rapidly ascend-ing to high altitude areas. Methods Fifty healthy male Wistar rats were randomly divided into 5 groups ( A to E) and intestinal epithelial cell injury in the models of rats with hypobaric hypoxia were established in decompression chamber. Autophagy inhibitor 3-MA was employed for drug intervention. Behavioral change of rats was observed,the intestinal tissue injury was analyzed by HE staining,and the expressions of autophagy-related protein LC-3 and Beclin-1 were de-tected by immunohistochemistry,and the mRNA expressions of LC-3 and Beclin-1 were quantified by RT-PCR. Results The injury of intestinal tissue was significantly aggravated in 3-MA group,the expressions of autophagy-related pro-tein LC-3 and Beclin-1 and corresponding mRNAs were also significantly lower in 3-MA group. Conclusion 3-MA may aggravate the damage to intestinal epithelial cells by inhibiting the autophagy in hypoxic rats rapidly ascending to high altitude areas. Autophagy may play a pivotal role in the protection of intestinal epithelial cell in high altitude areas.