兰州大学机构库 >学院待认领
鞘内注射 KN-93 对神经病理性疼痛大鼠脊髓背角pCREB表达的影响
Alternative TitleThe effect of pre-emptive intrathecal KN-93 on the expression of pCREB in spinal dorsal horn in a rat model of neuropathic pain
王迎斌
Thesis Advisor马永丰 ; 石翊飒
2008-05-15
Degree Grantor兰州大学
Place of Conferral兰州
Degree Name硕士
Keyword钙-钙调蛋白依赖性蛋白激酶类 神经病理性疼痛 DNA结合蛋白 环AMP反应性 注射 脊髓
Abstract目的1.观察钙/钙调蛋白依赖性蛋白激酶Ⅱ (Calcium/calmodulin-dependent protein kinase Ⅱ,CaMK Ⅱ) 抑制剂KN-93对神经病理性疼痛大鼠热痛觉过敏的影响,研究KN-93在脊髓水平是否具有抗神经病理性疼痛的作用。2、观察钙/钙调蛋白依赖性蛋白激酶Ⅱ (CaMK Ⅱ) 抑制剂KN-93对脊髓背角pCREB 表达的影响,探讨KN-93对慢性神经病理性疼痛的作用机制。方法 采用健康雄性Wistar 大鼠 32 只(体重:180-220g),随机分为 4 组 (n=8),A组:假手术组+DMSO 切皮前一小时鞘内注射 5%二甲基亚砜(DMSO) 10μl ; B 组:假手术组+KN-93 切皮前一小时鞘内注射KN-93 10μl (50 μ g溶于5%二甲基亚砜10μl中 ); C 组: CCI 组+DMSO 切皮前一小时鞘内注射 5%DMSO 10μl; D 组:CCI 组+ KN-93 切皮前一小时鞘内注射 KN-93 10μl ( 50 μg溶于5%二甲基亚砜10μl中 )。实验分两部分进行, 第一部分 各组分别在术前和术后 3 天用热痛刺激仪测定各组大鼠术侧热痛敏实验潜伏期( PWL )及基础值; 第二部分 术后 4 天和 7 天各组随机处死 4 只大鼠,取大鼠 L4-5 脊髓段进行免疫组织化学染色,对脊髓背角pCREB 染色阳性神经元进行记数分析。结果:第一部分,各组术后 3 天热痛敏阈值(PWL)与术前基础值比较均有不同程度减少,其差异有统计学意义 (P﹤0.05);术后 3 天 C 组与其他三组比较 PWL 值明显减少,其差异亦有统计学意义( P﹤0.05 ), A、B、D三组组间比较PWL值无统计学意义(P > 0.05)。第二部分,术后 4 天与 7天四组免疫组化分析结果比较: C 组脊髓背角 pCREB 表达最强,与其他三组比较明显增强( P﹤0.05 ),A、B、D三组组间比较pCREB表达无统计学意义(P > 0.05)。结论:1、鞘内预注射 KN-93 能明显减轻慢性坐骨神经松结扎大鼠热痛敏,提示钙/钙调蛋白依赖性蛋白激酶Ⅱ抑制剂KN-93在脊髓水平具有抗神经病理性疼痛的作用。2、鞘内预注射 KN-93可抑制 CCI 大鼠脊髓背角磷酸化 CREB 的表达,提示钙/钙调蛋白依赖性蛋白激酶Ⅱ在脊髓水平介导神经病理性疼痛的作用与促进脊髓背角磷酸化 CREB 的释放有关。
Other AbstractObjective To observe the effect of a specific CaMKⅡ inhibitor KN-93 on thermal hyperalgesia in a rat model of the chronic constriction injury of the sciatic nerve and evaluate the role played by the CaMKⅡ at the spinal cord level. By observing the expression of pCREB in the spinal cord dorsal horn in a rat model of the chronic constriction injury of the sciatic nerve and evaluate the role played by the CaMKⅡ in the mechanism of neuropathic pain at the spinal cord level. Methods Thirty-two adult male Wistar rats weighting 180-220g were randomly divided into four groups with 8 animals in each group: In group A sham operation rats received a bolus of 5% DMSO 10μl in an hour before sham operation; In group B sham operation rats received a bolus of KN-93 50μg (dissolved in 5% DMSO 10μl ); In group C CCI rats received a bolus of 5% DMSO 10μl; In group D CCI rats received a bolus of KN-93 50μg. The experiment was performed in 2 parts. In part one the paw withdrawal thermal latency (PWL) were measured by a hot plate test(55℃) before baseline and 3 days after surgery. In part two the animals were randomly killed after operation 4 or 7 days and lumbar(L4-5)segment of spinal cord was removed for determination of pCREB expression in the dorsal horn neurons of spinal cord using immuno-histochemistry technique. Results The paw withdrawal thermal latency (PWL) were measured the day before operation (baseline) .There is no difference between each group before operation (P<0.05).There is no difference about PWL among group A、B and D after operation 4 days(P﹥0.05). Comparing with other groups PWL of group C was significant decreasing. After operation 4 days and 7 days. In group A and B pCREB expression in spinal dorsal horn was weak. There is no difference in two groups (P﹥0.05). In group C pCREB expression positive neurons was strongest and much more increasing than group D(P﹤0.05). Conclusion Intrathecal KN-93 provides analgesia in CCI rats and significantly attenuated the activation of pCREB in the spinal cord dorsal horn induced by CCI , This study shows that the neuropathic pain mediated by CaMKⅡ is related to the release of cyclic AMP response element binding protein in spinal.
URL查看原文
Language中文
Document Type学位论文
Identifierhttps://ir.lzu.edu.cn/handle/262010/222854
Collection学院待认领
Affiliation临床医学院
Recommended Citation
GB/T 7714
王迎斌. 鞘内注射 KN-93 对神经病理性疼痛大鼠脊髓背角pCREB表达的影响[D]. 兰州. 兰州大学,2008.
Files in This Item:
There are no files associated with this item.
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Altmetrics Score
Google Scholar
Similar articles in Google Scholar
[王迎斌]'s Articles
Baidu academic
Similar articles in Baidu academic
[王迎斌]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[王迎斌]'s Articles
Terms of Use
No data!
Social Bookmark/Share
No comment.
Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.