Possible mechanisms of cholecystokinin promoting sciatic nerve regeneration

doi:10.3969/j.issn.2095-4344.2014.11.010

Abstract

Abstract:

BACKGROUND: Previous studies have found that cholecystokinin octapeptide (CCK-8) can promote the regeneration after sciatic nerve injury in rats, but the exact mechanism remains unclear.

OBJECTIVE: To screen effective indicators and analyze the mechanism of CCK-8 promoting sciatic nerve regeneration from the perspective of nerve growth factor and nerve regeneration microenvironment.

METHODS: Healthy Sprague-Dawley rats, for the preparation of unilateral sciatic nerve transection injury model, were randomly divided into two groups. In the CCK-8 group, the animal model received intraperitoneal injection of CCK-8 (8 nmol/kg) for consecutive 7 days, while the control group was injected with equal volume of normal saline. The nerve growth factor expression, inducible nitric oxide synthase in the spinal cord, serum superoxide dismutase activity and malondialdehyde concentration, as well as apoptotic cells in spinal cord were all detected.

RESULTS AND CONCLUSION: In the CCK-8 group, nerve growth factor expression was higher than that in the control group (P < 0.01), while inducible nitric oxide synthase and the number of apoptotic cells were lower (P < 0.01), serum superoxide dismutase activity was higher but malondialdehyde concentrations was lower (P < 0.01, 0.05). The mechanisms of CCK-8 promoting sciatic nerve regeneration include protecting neurons, anti-apoptosis, inhibiting inflammatory response, anti-NO and anti-oxidation, reducing malondialdehyde, and alleviating free radical damage, as well as stimulating nerve growth factor expression and release.

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

全文链接：

Key words: sciatic nerve, cholecystokinin, apoptosis, nerve growth factor

CLC Number:

R394.2

Chen Xuan-huang, Li Rong-yi, Zhang Guo-dong, Lin Hai-bin, Wu Xian-wei, Lin Yu-jin, Zheng Feng . Possible mechanisms of cholecystokinin promoting sciatic nerve regeneration[J]. Chinese Journal of Tissue Engineering Research, 2014, 18(11): 1700-1705.

Figures/Tables 2

2.1 实验动物数量分析纳入96只实验大鼠均进入结果分析。 2.2 局部神经生长因子蛋白的表达免疫组化实验神经生长因子蛋白阳性信号呈棕黄色，细胞结构呈蓝色。结果发现八肽胆囊收缩素治疗组损伤侧远端坐骨神经组织神经生长因子蛋白表达阳性呈棕黄色着色(图1A1)，在对照组损伤侧远端坐骨神经组织神经生长因子蛋白少许表达，着色淡(图1A2)。从神经生长因子的表达面积和密度看，八肽胆囊收缩素治疗组神经生长因子蛋白表达优于对照组(表1)，差异有显著性意义(P < 0.01，图2)。说明坐骨神经损伤后，应用八肽胆囊收缩素可促进局部神经生长因子的分泌、表达。 2.3 脊髓诱导型一氧化氮合酶的表达免疫组化检测结果以胞浆出现棕黄色颗粒为阳性反应，八肽胆囊收缩素治疗组诱导型一氧化氮合酶表达(图1B1)较对照组少(图1B2)，两组对比差异有非常显著性意义(P < 0.01，表1，图3)。说明坐骨神经损伤后应用八肽胆囊收缩素能减少诱导型一氧化氮合酶表达，进而促进神经再生。 2.4 血清超氧化物歧化酶及丙二醛浓度测定结果两组对比差异有显著性意义(P < 0.05，0.01)，与对照组比，八肽胆囊收缩素治疗组血清超氧化物歧化酶活性高，血清丙二醛浓度低(表1，图4)。说明坐骨神经损伤后应用八肽胆囊收缩素能提升体内超氧化物歧化酶活力，降低有害物质丙二醛的浓度，进而提高了机体清除氧自由基的能力，改善氧化应激状态。 2.5 脊髓细胞凋亡指数比较 TUNEL法细胞核染色呈棕黄色者为阳性细胞，即凋亡细胞，两组脊髓细胞凋亡指数比较差异有非常显著性意义(P < 0.01，表1，图5)。八肽胆囊收缩素治疗组神经细胞凋亡(图1C1)较对照组少(图1C2)。说明坐骨神经损伤后应用八肽胆囊收缩素能减少脊髓细胞凋亡。"

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