内质网应激与凋亡在糖尿病周围神经病变中的表达变化

doi:10.6040/j.issn.1671-7554.0.2017.490

摘要/Abstract

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(P<0.001),运动神经传导速度明显减慢(P<0.001);内质网应激蛋白CHOP、PERK表达水平增加(P=0.003, P<0.001);促凋亡蛋白Bax、Caspase-12表达增加(P<0.001, P<0.001),抗凋亡蛋白Bcl-2表达降低(P<0.001)。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(P<0.001, P=0.01), Bax、Caspase-12表达增加(P<0.001, P=0.002),Bcl-2表达水平降低(P<0.001)。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。

关键词: Wistar, 凋亡, 内质网应激, 糖尿病周围神经病变, 运动神经传导速度, 大鼠

Abstract: Objective To observe endoplasmic reticulum stress(ERS)and apoptosis-related protein in diabetic peripheral neuropathy(DPN)in animal models and to investigate the possible mechanism. Methods A total of 36 Wistar rats were divided into 3 groups: control group(n=12, CON group), diabetic mellitus group (n=12, DM group), and diabetic peripheral neuropathy group(n=12, DPN group). The blood glucose(BG)and motor nerve conduction velocity(MNCV)were measured. The proteins, including CHOP, PERK, Bax, Bcl-2 and Caspase-12 were determined with Western blotting. Results Compared with CON group, the DM group had greatly increased BG and significantly decreased MNCV(both P<0.001); higher expression of CHOP, PERK, Bax, and Caspase-12(P=0.003, P<0.001, P<0.001, P<0.001), but lower expression of Bcl-2(P<0.001). Compared with the DM group, the DPN group had elevated expression of CHOP, PERK, Bax, and Caspase-12(P<0.001, P=0.001, P<0.001, P=0.002), but lower expression of Bcl-2(P<0.001). Conclusion In animal models of DPN, the ERS in sciatic nerve is increases, and the level of apoptosis also increases, indicating that ERS is involved in the occurrence of DPN.

Key words: Rats,Wistar, Motor nerve conduction velocity, Endoplasmic reticulum stress, Apoptosis, Diabetic peripheral neuropathy

中图分类号:

R587.1

张亮,徐敏,庄向华,娄福臣,娄能俊,吕丽,郭文娟,郑凤杰,陈诗鸿. 内质网应激与凋亡在糖尿病周围神经病变中的表达变化[J]. 山东大学学报（医学版）, 2017, 55(8): 13-17.

ZHANG Liang, XU Min, ZHUANG Xianghua, LOU Fuchen, LOU Nengjun, LÜ Li, GUO Wenjuan, ZHENG Fengjie, CHEN Shihong. An investigation of endoplasmic reticulum stress and apoptosis in diabetic peripheral neuropathy[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(8): 13-17.

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