内质网应激与凋亡在糖尿病周围神经病变中的表达变化

发布时间：2019-01-07 11:45

【摘要】：目的通过构建糖尿病周围神经病变(DPN)大鼠模型,观察DPN大鼠坐骨神经中内质网应激与凋亡相关蛋白表达变化,探讨内质网应激在DPN中的可能作用机制。方法取36只8周龄雄性Wistar大鼠,适应性饲养1周后,选取其中12只作为正常对照组(CON组),其余24只通过高脂饮食结合腹腔注射链脲佐菌素(STZ)方法,将大鼠分别构建成糖尿病组(DM组,12只)、DPN组(12只)模型。造模成功后检测3组大鼠血糖与坐骨神经传导速度,并取大鼠坐骨神经,采用Western blotting方法检测内质网应激蛋白CHOP、PERK与凋亡相关蛋白Bax、Caspase-12、Bcl-2表达水平。结果与CON组比较,DM组血糖水平明显升高(P0.001),运动神经传导速度明显减慢(P0.001);内质网应激蛋白CHOP、PERK表达水平增加(P=0.003,P0.001);促凋亡蛋白Bax、Caspase-12表达增加(P0.001,P0.001),抗凋亡蛋白Bcl-2表达降低(P0.001)。与DM组比较,DPN组大鼠坐骨神经内质网应激蛋白CHOP、PERK表达水平增加(P0.001,P=0.01),Bax、Caspase-12表达增加(P0.001,P=0.002),Bcl-2表达水平降低(P0.001)。结论 DPN大鼠模型坐骨神经存在明显的内质网应激反应增加、凋亡上调,内质网应激参与了DPN的发生过程。
[Abstract]:Objective to observe the changes of endoplasmic reticulum stress and apoptosis-related protein expression in sciatic nerve of (DPN) rats with diabetic peripheral neuropathy and to explore the possible mechanism of endoplasmic reticulum stress in DPN. Methods Thirty-six 8-week-old male Wistar rats were fed adaptively for one week, 12 of them were used as normal control group (CON group), the other 24 rats were treated by high-fat diet and intraperitoneal injection of streptozotocin (STZ). The rats were divided into diabetic group (DM group) and), DPN group (12 rats). The blood glucose and the conduction velocity of sciatic nerve were measured after the model was established. The expression of endoplasmic reticulum stress protein (CHOP,PERK) and apoptosis-related protein (Bax,Caspase-12,Bcl-2) were detected by Western blotting method. Results compared with the CON group, the blood glucose level in the DM group was significantly increased (P0.001), the motor nerve conduction velocity was significantly decreased (P0.001), the expression of endoplasmic reticulum stress protein CHOP,PERK was increased (P0. 003 + P0. 001). The expression of pro-apoptotic protein Bax,Caspase-12 increased (P0.001 + P0.001), and the expression of anti-apoptotic protein Bcl-2 decreased (P0.001). Compared with DM group, the expression of ER stress protein CHOP,PERK, Bax,Caspase-12 and Bcl-2 in DPN group were increased (P0.001P0. 01) and decreased (P0. 001). Conclusion there are obvious endoplasmic reticulum stress responses and up-regulation of apoptosis in sciatic nerve of DPN rats. Endoplasmic reticulum stress is involved in the process of DPN.
【作者单位】：山东大学第二医院内分泌科;
【基金】：国家自然科学基金(81670753) 中华医学会临床医学科研专项资金(13020230408) 山东大学第二医院种子基金(S2014010004)
【分类号】：R587.2

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