雄激素对老年大鼠胃粘膜线粒体功能的影响及机制  

Effect and mechanism of androgens on mitochondrial functions of gastric mucosa in aged rats

作　　者：郭朋璐 董曼[1] 严晓红 康洁 GUO Penglu;DONG Man;YAN Xiaohong;KANG Jie(Department of Gastroenterology,Harrison International Peace Hospital,Hengshui 053000,China;Hebei Yiling Hospital,Shijiazhuang 050000)

机构地区：[1]哈励逊国际和平医院,消化内科内镜室,河北衡水053000 [2]河北省以岭医院,石家庄050000

出　　处：《中国比较医学杂志》2021年第11期21-26,34,共7页Chinese Journal of Comparative Medicine

基　　金：2018河北省医学科学研究课题计划项目(20180894)。

摘　　要：目的探讨雄激素对睾丸切除(GDX)老年大鼠胃粘膜线粒体功能的影响及机制。方法 36只SD雄性大鼠随机分为3组:假手术组(Sham,n=12)、模型组(GDX,n=12)和补充雄激素的模型大鼠(n=12)。造模大鼠行GDX,造模后雄激素组灌胃睾丸酮(13.6 mg/(kg·d),溶于芝麻油中)。假手术组和模型组大鼠使用芝麻油进行相同的治疗。治疗结束后收集胃组织标本,分别采用试剂盒检测胃粘膜线粒体中Mn-SOD、GSH-Px、GSH、GSSG、GSH/GSSG和ROS水平,罗丹明123荧光法检测线粒体膜电位,流式细胞仪检测细胞凋亡。体外试验以人永生胃粘膜细胞GES-1为研究对象,应用H_(2)O_(2)诱导细胞损伤,考察雄激素和ALDH2抑制剂Disulfiram对细胞活力和凋亡影响。结果与Sham组相比,GDX组ROS、GSSG水平、胃粘膜细胞凋亡和裂解的Caspase-3、细胞质Cyt c蛋白表达显著增加(P<0.05),而Mn-SOD、GSH-Px、GSH、GSH/GSSG水平、线粒体膜电位、ATP水平和线粒体Cyt c蛋白、ALDH2蛋白表达显著降低(P<0.05)。在雄激素治疗后,GDX老年大鼠上述变化显著逆转(P<0.05)。体外实验中,雄激素处理显著逆转了H_(2)O_(2)对GES-1细胞的损伤作用(P<0.05);然而,当联合加入Disulfiram时,雄激素的治疗活性明显降低(P<0.05)。结论雄激素缺乏导致老年大鼠胃粘膜细胞线粒体功能障碍和线粒体ROS积累增加,诱导胃黏膜细胞凋亡,这种损害作用至少部分与ALDH2的抗氧化功能抑制有关。Objective To investigate the effect and mechanism of androgens on mitochondrial functions of gastric mucosa in aged gonadectomized male(GDX) rats. Methods 36 male SD rats were randomly divided into three groups: sham operation group(Sham, n=12), model group(GDX, n=12) and androgen-supplemented model rats(n=12). GDX rats were used for modeling. After modeling, the AG group was administered testosterone(13.6 mg/(kg·d), dissolved in sesame seed oil). Rats in sham operation and model groups were treated with sesame seed oil. After the treatment, gastric tissue samples were collected and the levels of Mn-SOD, GSH-Px, GSH, GSSG, GSH/GSSG and ROS in gastric mucosa mitochondria were measured by kits, the mitochondrial membrane potential was measured by rhodamine 123 fluorescence, and apoptosis was analyzed by flow cytometry. In vitro, GES-1 cells were used as the research object. H_(2)O_(2)was used to induce cellular injury. The effects of androgens and ALDH2 inhibitor disulfiram on cell viability and apoptosis were investigated. Results Compared with Sham group, ROS and GSSG levels, gastric mucosal cell apoptosis and cleaved Caspase-3 and cytoplasmic Cyt c protein expression were significantly increased in the GDX group(P<0.05), while Mn-SOD, GSH-PX, GSH and GSH/GSSG levels, the mitochondrial membrane potential, ATP level and mitochondrial Cyt c and ALDH2 protein expression were decreased significantly(P<0.05). After androgen treatment, the above changes in GDX elderly rats were reversed significantly(P<0.05). In vitro, androgen treatment significantly reversed damage induced by H_(2)O_(2)in GES-1 cells(P<0.05). However, when combined with Disulfiram, the therapeutic activity of androgen was reduced significantly(P<0.05). Conclusions Androgen deficiency leads to mitochondrial dysfunction and increased mitochondrial ROS accumulation in gastric mucosal cells of elderly rats and induces gastric mucosal cell apoptosis, which is at least partly related to inhibition of the antioxidant function of ALDH2.

关 键 词：雄激素 老年大鼠 胃粘膜 线粒体 睾丸切除 

分 类 号：R-33[医药卫生]