兰州大学机构库 >学院待认领
cAMP/Epac2/Akt信号通路激活促进大鼠脊髓损伤的修复
Alternative TitleThe activation of cAMP/Epac2/Akt kinase signaling pathway promotes the repair of spinal cord injury in rats
张涛
Thesis Advisor文益民
2013-05-15
Degree Grantor兰州大学
Place of Conferral兰州
Degree Name硕士
Keyword脊髓损伤 环磷腺苷 Epac2 信号通路 大鼠
Abstract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Allens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[0.5mg/(kg·d)]、B组给予等量10%DMSO(体积分数)、C组给予8-CPT-2′-O-Me-cAMP[0.5mg/(kg·d)]加LY294002 [0.2mg/(kg·d)] 各7天。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( P<0.01),低于D组( P<0.01)。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( P<0.01)和D组( P<0.01)的Epac2 mRNA。A组Akt mRNA表达高于B组( P<0.01)、C组( P<0.01)和D组( P<0.01)。A组Nestin、NF200、mRNA表达在各期均高于B、C、D组( P<0.01)。A、B、C组GFAP mRNA表达差异无意义。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。
Other AbstractObjective: To investigate the mechanism of cAMP derivative activated Epac2/Akt signal pathway in the mammalian after spinal cord injury. Methods: Ninety-six rats were randomly divided into 4 groups. The rats in groups A, B and C were made the SCI models. The rats were subjected to the different administration for 7 days in every group. Locomotor activity was evaluated using the BBB rating scale and the expressions of spinal cord cell marker and the pathway factors were detected at the every weeks. Results: The BBB scores in group A showed higher than those in groups B and C. The mRNA expression of Epac2 in group A was higher than group B and group D, but was no different to group C. The mRNA expression of Akt in group A was higher than group B、C and D. The mRNA expression of Nestin and NF200 in group A were higher than group B、C and D. There were no different mRNA expression of GFAP between group A、B and C. The similar changes were found by assay of Integrated optical density of immunofluorescence. Conclusion: The derivative of cAMP can activate the Epac2/Akt pathway to induce neural stem cells to proliferate and differentiate into neurons and enhances the healing of SCI in rats.
URL查看原文
Language中文
Document Type学位论文
Identifierhttps://ir.lzu.edu.cn/handle/262010/224206
Collection学院待认领
Affiliation临床医学院
Recommended Citation
GB/T 7714
张涛. cAMP/Epac2/Akt信号通路激活促进大鼠脊髓损伤的修复[D]. 兰州. 兰州大学,2013.
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