高脂饮食对小鼠附睾内质网应激的影响及褪黑素的干预作用

摘要

目的 探讨内质网应激在高脂饮食引起的ApoE基因敲除小鼠附睾损伤中的作用及褪黑素(MT)的干预机制.方法 将12只ApoE基因敲除的C57BL/6J雄性小鼠随机分为高脂饮食组及MT处理组.高脂饮食组为ApoE基因敲除小鼠,给予高脂饮食；MT处理组给予高脂饲养外,并MT灌胃.以6只野生型C57BL/6J雄性小鼠作为对照组,给予普通饮食.饲养12w后,取附睾组织制片,HE染色观察附睾的病理学形态,免疫组化检测GRP78和CHOP的表达.结果 HE染色显示,高脂饮食组小鼠,附睾上皮细胞形态结构不清,细胞萎缩.对照组和褪黑素处理组小鼠附睾上皮细胞形态结构完整,细胞排列整齐.免疫组化显示高脂饮食组小鼠附睾中GRP78、CHOP表达增强(P＜0.01).MT处理组和高脂饮食组相比,附睾中GRP78、CHOP表达下调(P＜0.01).结论 内质网应激参与高脂饮食导致的附睾损伤；MT可能通过抑制附睾内质网应激,减轻高脂饮食对小鼠附睾的损伤.%Objective To investigate the effect of endoplasmic reticulum stress on epididymal damage caused by high fat diet in ApoE-knockout mice and the influence effect of melatonin. Methods Twelve ApoE-knockout C57BL/6J male mice fed with high-fat diet alone( High-fat diet group) ,or with high-fat diet and melatonin(melatonin-treated group). Six ApoE wild-type C57BL/6J male mice were fed with normal diet,served as controls. At the end of 12 weeks, One epididymis was imbedded in paraffin and processed for histopathological examination. Testicular samples were cut as 5-um-thick sections and stained with haematoxylin-eosin(HE). Expression of GRP78 and CHOP in epididymis was detected by immuno-histochemistry staining. Results HE staining reveals the morphological structure of epididymis epithelium was complete in the in the control group and melatonin-treat group,and was disrupted in the high-fat diet group. Epididymisal tissues express abundant GRP78 and CHOP in the high-fat diet group than in control group(P<0. 01). Compared with high-fat diet group, the epression of GRP78 and CHOP in melatonin-treat group were remarkably reduced(P<0. 01). Conclusion Endoplasmic reticulum stress has involved in the high-fat diet induced damage of epididymis. Melatonin has markedly protective effect on epididymal injury by decreasing the expression of GRP78 and CHOP.