cAMP derivative promotes repair of spinal cord injury in rats by activating Epac2/Akt kinase signaling pathway

张涛; 文益民; 魏祥科; 李含

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cAMP derivative promotes repair of spinal cord injury in rats by activating Epac2/Akt kinase signaling pathway

更新时间：2026-01-09

- cAMP derivative promotes repair of spinal cord injury in rats by activating Epac2/Akt kinase signaling pathway
- Journal of Army Medical University Vol. 34, Issue 24, Pages: 2493-2497(2012)
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  CLC： R-332;R363;R651.2
- Published：2012
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张涛,文益民,魏祥科,李含.cAMP衍生物特异性激活Epac2/Akt信号通路促进大鼠脊髓损伤的修复[J].陆军军医大学学报(原第三军医大学学报),2012,34(24):2493-2497.

　Zhang Tao,Wen Yimin,Wei Xiangke,Li Han.cAMP derivative promotes repair of spinal cord injury in rats by activating Epac2/Akt kinase signaling pathway[J].J Amry Med Univ (J Third Mil Med Univ),2012,34(24):2493-2497.
张涛,文益民,魏祥科,李含.cAMP衍生物特异性激活Epac2/Akt信号通路促进大鼠脊髓损伤的修复[J].陆军军医大学学报(原第三军医大学学报),2012,34(24):2493-2497. DOI：

　Zhang Tao,Wen Yimin,Wei Xiangke,Li Han.cAMP derivative promotes repair of spinal cord injury in rats by activating Epac2/Akt kinase signaling pathway[J].J Amry Med Univ (J Third Mil Med Univ),2012,34(24):2493-2497. DOI：

摘要

目的研究应用cAMP衍生物特异性激活Epac2/Akt信号通路在哺乳动物脊髓损伤中的病理和生理机制。方法 96只成年健康雌性SD大鼠，完全随机分为4组（n=24），A、B、C组均采用改良Allen重物打击法制备大鼠脊髓损伤模型。A组给予8-CPT-2′-O-Me-cAMP 0.5 mg/(kg·d)、B组给予等量10%(体积分数)DMSO、C组给予8-CPT-2′-O-Me-cAMP 0.5 mg/(kg·d)加LY294002 0.2 mg/(kg·d) 各7 d。D组为正常对照组。各组分别于1、2、3、4周采用BBB评分法评估大鼠后肢功能恢复情况，各时间点取材行HE染色、免疫荧光、实时荧光定量 PCR 检测脊髓细胞标志物（Nestin、NF200、GFAP）和通路因子(Epac2、Akt)的表达。结果 A组大鼠在术后1～4周BBB评分持续升高，均高于B、C组(P0.01)，低于D组(P0.01)。在1、2、3周，A组Epac2 mRNA表达与C组Epac2 mRNA表达差异无意义，但高于B组(P0.01)和D组(P0.01)。A组Akt mRNA表达高于B、C、D组(P0.01)。A组Nestin、NF200 mRNA表达在各期均高于B、C、D组(P0.01)。A、B、C组GFAP mRNA表达差异无统计学意义。HE染色可见A、B、C组造模后脊髓组织结构疏松，有大量空洞形成。免疫荧光染色并进行积分光密度值分析，其结果与实时荧光定量PCR检测结果相符。结论在哺乳动物脊髓损伤后应用cAMP衍生物能够特异性激活Epac2/Akt通路，促使神经干细胞分化和神经细胞增殖，有助于脊髓修复。

Abstract

Objective To investigate the underlying mechanism of cAMP derivative（8-CPT-2′-O-Me-cAMP） in the physiology and pathology of spinal cord injury (SCI). Methods Ninety-six adult healthy female Sprague-Dawley rats were randomly divided into 4 groups (n=24). The rats from groups A

B and C were inflicted to SCI models with a modified Allen’s method. The rats were subjected to administer the derivative of 0.5 mg/(kg·d) in group A

10% DMSO at equal volume in group B

and the derivative and LY294002 of 0.2 mg/(kg d) in group C respectively for 7 d. The rats in groups D served as normal control. Locomotor activity was evaluated by using the Basso-Beattie-Bresnahan (BBB) score test at 1

3 and 4 weeks postoperatively. The expression of spinal cord cell markers

Nestin

glial frillary acidic protein (GFAP) and NF200

and of pathway factors

Epac2 and Akt were detected at the every week by HE staining

immunofluorescence analysis and real-time fluorescence PCR analysis. Results The BBB scores in group A showed a steady increase in the postoperative 1 to 4 weeks and were significantly higher than those in groups B and C (P0.01)

but were lower than that in group D (P0.01). In the postoperative 1st to 3th weeks

the mRNA expression of Epac2 in group A was significantly higher than that of group B (P0.01) and group D (P0.01)

but was not different with that of group C. The mRNA expression of Akt in group A was significantly higher than those of groups B

C and D (all P0.01). The mRNA expression of Nestin and NF200 in group A were significantly higher than those of groups B

C and D (P0.01) at 1 to 4 weeks. There was no difference in GFAP mRNA expression among groups A

B and C. The similar changes were found by immunofluorescence analysis. A lot of cavities were observed in spinal cord tissues by HE staining in groups A

B and C. Conclusion The derivative of cAMP activates the Epac2/Akt pathway to induce neural stem cells to proliferate and differentiate into neurons

and thus enhances the healing of SCI in rats.

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