糖尿病大鼠坐骨神经内质网应激相关分子的动态变化  

Dynamic change of endoplasmic reticulum stress-related molecules in the sciatic nerve of diabetic rats

作　　者：谢映红[1] 王巍[2] 

机构地区：[1]中国人民解放军第202医院综合科,辽宁沈阳110003 [2]中国人民解放军第202医院内分泌科,辽宁沈阳110003

出　　处：《解剖科学进展》2016年第1期45-48,共4页Progress of Anatomical Sciences

基　　金：辽宁省自然科学基金(2013020220)

摘　　要：目的研究糖尿病病变过程中内质网应激分子在坐骨神经中的动态表达。方法采用高脂饲料喂养联合腹腔注射链脲佐菌素(Streptozotocin,STZ)35mg/kg复制糖尿病大鼠模型。实验分为正常对照组及糖尿病组,各组分别在糖尿病造模成功后第4周、8周、12周、16周取坐骨神经。应用透射电镜观察坐骨神经形态,采用qRT-PCR及Western blot方法检测GRP78、PERK、IRE1a、ATF6表达水平。结果血糖升高后蜩坐骨神经出现结构扭曲、形态不规则,至16周坐骨神经可见髓鞘厚度不均一,较重者可见髓鞘板层分离现象。GRP78 mRNA及蛋白表达水平在血糖升高后8周明显高于正常对照组(P<0.05),IRE1a、PERK蛋白表达水平分别在血糖升高后8周、12周明显高于正常对照组(P<0.05)。ATF6蛋白表达水平随着病程进展呈现增高趋势,但与正常组比较差异无显著性(P>0.05)。结论GRP78、PERK、IRE1a内质网应激分子过表达可能参与糖尿病周围神经的损伤。Objective To explore the dynamic change of endoplasmic reticulum stress-related molecules GRP78,PERK,IRE1 a and ATF6 in the sciatic nerve of diabetic rats.Methods Eighty male Sprague Dawley（SD） rats were randomly divided into normal control group（NC,n=32,fed with standard chow） and diabetes mellitus group（DM,n=48）induced by intraperitoneal injection of streptozotocin（STZ,35mg/kg after 4 weeks of high-fat chow feeding）.The sciatic nerves were isolated 4 weeks,8 weeks,12 weeks,and 16 weeks after elevation of blood glucose.The expressions of GRP78,PERK,IRE1 a,ATF6 mRNA and protein were detected by qRT-PCR and Western blot respectively.The morphology of sciatic nerve was observed by electron microscope.Results The shape distortion of sciatic nerve appeared in diabetic rats 8weeks after elevation of blood glucose,uneven thickness of myelin sheath and isolation of myelin lamellar structure were found in sciatic nerve of diabetic rats at 16 weeks after elevation of blood glucose.The expression levels of GRP78 mRNA and protein were obviously higher in DM group than in NC group 8 weeks after elevation of blood glucose（P〈0.05）,reached peak 12 weeks and showed a downward trend 16 weeks after elevation of blood glucose.The expression levels of IRE 1 a and PERK proteins were obviously higher in DM group than in NC group 8 weeks and 12 weeks after elevation of blood glucose（P〈0.05） and continued to increase to 16 weeks.The expression level of ATF6 protein was no difference between diabetic groups and normal control（P〈0.05）.Conclusion Endoplasmic reticulum stressrelated molecules（GRP78 、 PERK 、 IRE1a） might be involved in the peripheral nerve injury of diabetic rats.

关 键 词：内质网应激 糖尿病周围神经病变 大鼠 

分 类 号：R587.1[医药卫生—内分泌]