兰州大学机构库 >学院待认领
ATP通过激活Akt/mTOR/ STAT3信号转导通路促进脊髓损伤修复
Alternative TitleATP promotes the repair of spinal cord injury by activating the Akt/mTOR/STAT3 signal transduction pathway in rats
孙振刚
Thesis Advisor文益民
2010-05-09
Degree Grantor兰州大学
Place of Conferral兰州
Degree Name硕士
Keyword丝氨酸/苏氨酸蛋白激酶 哺乳类动物雷帕霉素靶蛋白 信号转录和转导激活因子3 三磷酸腺苷 脊髓损伤 信号通路
Abstract目的 脊髓损伤(SCI)后,内源性神经干细胞(NSCs)能够分化成神经元促进脊髓愈合,但其分子机制尚不清楚。现研究ATP激活Akt/mTOR/STAT3通路在SCI中的生理和病理机制。 方法 取128只健康成年雌性SD大鼠,体重250~300 g,随机分为4组(n = 32):A、B、C组用改良Allen重物打击法制作T8~10 SCI模型后,A组以ATP、B组以等量生理盐水、C组以ATP加雷帕霉素分别治疗7 d;D组仅行椎板切除术,不损伤脊髓,等量生理盐水治疗7 d。术后1、2、3、4周采用BBB评分法评估大鼠后肢运动功能恢复情况,各时间点取材行免疫组织化学、Western-blot、实时荧光定量PCR检测脊髓细胞标志物NSE、Nestin、GFAP和通路因子Akt、mTOR、STAT3的表达。结果 术后1~4周A组大鼠BBB评分呈持续增高趋势,均高于B、C组,低于D组,差异有统计学意义(P < 0.05)。免疫组织化学、Western-blot、实时荧光定量PCR检测均显示,术后1~4周,A组大鼠Akt、mTOR、STAT3、NSE表达持续增高,Nestin表达逐渐降低,均高于B、C、D组,差异有统计学意义(P < 0.05);而A组GFAP表达持续增高,均低于B、C组,高于D组(P < 0.05)。各时间点B、C组各指标表达与D组比较差异均有统计学意义(P < 0.05)。 结论 在大鼠体内ATP能激活Akt/mTOR/STAT3通路诱导内源性NSCs增殖、分化为神经元,有助于SCI的愈合。
Other AbstractObjective Endogenic neural stem cells (NSCs) can differentiate into neurons leading to the healing of SCI, however, its molecular mechanism is not clear in SCI. In this study, we aimed to investigate the mechanism of ATP-activated serine/threonine-specific protein kinase (Akt)/mammalian target of rapamycin (mTOR)/signal transducer and activator of transcription 3 (STAT3) pathway in the physiology and pathology of spinal cord injury (SCI). Methods Adult specific pathogen-free female Sprague-Dawley rats (128) were randomly divided into four groups (n=32): Using a modified Allen’s stall to produce model of SCI at T8~10 in rats of group A, B, C. Group A, in which group rats were subjected to the administration of ATP, for 7 days; Group B, in which group rats were subjected to the administration of physiological saline (equal-volume), for 7 days; Group C, in which group rats were subjected to the administration of ATP and rapamycin, for 7 day; Group D, in which group rats were subjected to laminectomy in combination with the administration of physiological saline (equal-volume), for 7 days. Locomotor activitys of rats were evaluated using the Basso, Beattie, and Bresnahan (BBB) rating scale at postoperative 1, 2, 3, 4 weeks. Then, detecting the expressions of spinal cord cell marker [Nestin, neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP)] and the mTOR pathway factors (Akt, mTOR, STAT3) in all of groups at postoperative 1, 2, 3, 4 weeks by Immunohistochemistry analysis, Western blotting assay and real time RT-PCR analysis. Results The BBB scores of rats in group A showed a steady increase in postoperative 1~4 weeks and were all significantly higher compared with that found in group B and C, but were less than that of group D (P < 0.05). Analyzing Immunohistochemistry, Western blotting, real time RT-PCR results, in postoperative 1~4 weeks, the expression of Akt, mTOR, STAT3, NSE in rats of group A showed a steady increase, however, Nestin was gradually decreased, which were all significantly higher than that of group B, C, D (P < 0.05); The expression of GFAP showed a steady increase in group A and were all significantly less than that of group B and C, but were higher that of group D (P < 0.05). The differences of expression of each indicator between in group B and D or group C and D were statistically significant in 1~4 weeks (P < 0.05), the differences of Akt, P-Akt, mTOR, P-mTOR, STAT3, P-STAT3 between in group B and C by Western...
URL查看原文
Language中文
Document Type学位论文
Identifierhttps://ir.lzu.edu.cn/handle/262010/224220
Collection学院待认领
Affiliation临床医学院
Recommended Citation
GB/T 7714
孙振刚. ATP通过激活Akt/mTOR/ STAT3信号转导通路促进脊髓损伤修复[D]. 兰州. 兰州大学,2010.
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