Stronger expression of CHOP and caspase 12 in diabetic spinal cord injury rats

Stronger expression of CHOP and caspase 12 in diabetic spinal cord injury rats
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DOI:
10.1179/174313209x385707
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发表时间:
2009-12-01
影响因子:
1.9
通讯作者:
Fan, Shunwu
Fan, Shunwu
中科院分区:
医学4区
文献类型:
--
作者:
Wan, Shuanglin;Shi, Peihua;Fan, Shunwu

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目的:提示损伤性脊髓神经元细胞死亡与内质网应激有关。在这项工作中,我们探讨了糖尿病诱导大鼠更严重的脊髓损伤(SCI)和更强的内质网应激。方法:将45只Sprague-Dawley大鼠随机分为3组(假手术对照组、SCI组和糖尿病性SCI组)。尾静脉注射链脲佐菌素(30 mg/kg)诱导糖尿病;糖尿病模型诱导后4周,采用SCI组和糖尿病性SCI组大鼠减重挫伤模型;分别于24 h和7 d处死大鼠,采用免疫组化染色和实时逆转录定量聚合酶链反应法检测C/EBP同源转录因子蛋白(CHOP)、促凋亡蛋白及caspase 12的表达水平。结果:我们观察到糖尿病SCI组CHOP和caspase 12均高于SCI组。糖尿病还会导致严重的运动功能障碍,并随着Basso、Beattie和Bresnaha评分的降低而缓慢恢复。病理苏木精-伊红染色观察显示,糖尿病性脊髓损伤大鼠背白细胞进行性破坏,神经元再生少。讨论:这些结果提示糖尿病大鼠内质网应激增强可能是严重SCI发生的原因。[神经科学进展,2009;31日:1049 - 1055)
Objectives: It is suggested that the injury-induced cell death of neurons within the spinal cord is related with endoplasmic reticulum (ER) stress. In this work, we explored that diabetes induce more severe spinal cord injury (SCI) and stronger ER stress in rats.Methods: Forty-five Sprague-Dawley rats were divided into three groups at random (the sham operation control group, SCI group and diabetic SCI group). Streptozotocin was injected into the caudal vein (30 mg/kg) to induce diabetes; 4 weeks after diabetes model induction, using a weight-drop contusion model of SCI in SCI group and diabetic SCI group; then, rats were killed at 24 hours and 7 days, and the level of C/EBP homologous transcription factor protein (CHOP), a proapoptotic protein, and caspase 12 were determined by immunohistochemistry staining and real-time reverse transcription quantitative polymerase chain reaction analysis.Results: We observe that both CHOP and caspase 12 were higher in diabetic SCI group than in the SCI group. Diabetes also caused severe locomotor dysfunction and slowly recovered as their Basso, Beattie and Bresnaha scores lowered. Pathological hematoxylin-eosin staining observation also showed progressive disruption of the dorsal white and few neurons regeneration in diabetic SCI rats.Discussion: These results suggest that stronger ER stress in diabetic rats may be the reason for severe SCI observed. [Neurol Res 2009; 31: 1049-1055]