神经生长因子对颅脑外伤大鼠的抗炎作用机制  

Intranasal delivery of nerve growth factor attenuates neuroinflammation following traumatic brain injury in rats

作　　者：吕秋石[1] 郭芮兵[1] 姜永军[1] 叶瑞东[1] 樊新颖[1] 马敏敏[1] 李芸[1] 徐格林[1] 刘新峰[1] 

机构地区：[1]南京军区南京总医院神经内科,南京医学硕士210002

出　　处：《医学研究生学报》2014年第10期1020-1022,共3页Journal of Medical Postgraduates

基　　金：国家自然科学基金(31171016);南京军区南京总医院科研基金(2012005)

摘　　要：目的：颅脑外伤（traumatic brain injury， TBI）后炎症反应会引发神经系统功能紊乱，文中旨在探讨经鼻给予神经生长因子（ nerve growth factor ， NGF）对 TBI后大鼠炎症反应的作用及其机制。方法36只健康SD大鼠按随机数字表法分为假手术组、TBI模型组、治疗组，每组12只，TBI模型组和治疗组采用自由落体法撞击建立脑外伤模型，假手术组仅采用开颅窗后用骨蜡封闭。治疗组TBI后6 h经鼻给予NGF（50 g/d），TBI模型组及假手术组给予等量磷酸盐缓冲液（PBS，pH 7．4～7．5），每天给药1次，持续给药至大鼠被处死。各组分别于TBI后12 h、24 h各处死6只大鼠。测定大鼠伤侧皮质内IL-1β、TNF-α的表达量、核因子-κB（nuclear factor kappa B，NF-κB）的DNA结合活性及β-淀粉样蛋白（amyloid-β，Aβ42）的表达。结果 TBI后12 h和24 h治疗组大鼠IL-1β的表达量[（37．51±1．92、36．23±2．99）pg/mg]较TBI模型组[（70．65±3．10、68．85±8．10）pg/mg]明显降低（P＜0．05），TNF-α的表达量[（27．63±5．77、29．94±8．62）pg/mg]较TBI模型组[（47．12±7．38、56．15±11．20）pg/mg]显著减少（P＜0．05），TBI后12 h、24 h，经鼻给予NGF后，治疗组大鼠NF-κB DNA结合活性（111．62±0．49、131．52±0．88）较TBI模型组（135．26±0．60、149．86±0．49）显著降低（P＜0．05），伤侧皮质内Aβ42的表达（0．230±0．008、0．520±0．004）较TBI模型组（0．827±0．009、1．390±0．010）明显下降（P＜0．05）。结论经鼻给予NGF可控制TBI大鼠脑内的炎症反应，该作用机制可能与调节Aβ42/NF-κB通路相关。Objective Neuroinflammation following traumatic brain injury （TBI） may give rise to neurodisorder.This study aimed to investigate the effect of intranasal delivery of nerve growth factor （ NGF） on neuroinflammation following TBI and its action mechanism in rats. Methods Thirty-six male adult Sprague-Dawley rats were equally divided into a sham , a TBI, and a TBI＋NGF group.The rats in the TBI ＋NGF group were treated with NGF intranasally at 12 and 24 hours after TBI.The levels of IL-1βand TNF-αin the injured cerebral cortex were detected by ELISA , the DNA-binding activity of NF-κB evaluated by EMSA , and the expres-sion of amyloid-β（ Aβ42 ） determined by Western blot . Results NGF attenuated the inflammation following TBI .Compared with the TBI group, the level of IL-1βwas obviously decreased in the TBI ＋NGF group at 12 hours （70.65 ±3.10 vs 37.51 ±1.92） and 24 hours （68.85 ±8.10 vs 36.23 ±2.99, P〈0.05）, and so was that of TNF-α（47.12 ±7.38 vs 27.63 ±5.77 and 56.15 ±11.20 vs 29.94 ±8.62, P〈0.05）.The DNA-binding activity of NF-κB was reduced to 111.62 ±0.49 and 131.52 ±0.88, and the expression of Aβ42 to 0.23 ±0.008 and 0.52 ±0.004 at 12 and 24 hours respectively after treatment with NGF , both with statistically significant differences from the TBI group （P〈0.05）. Conclusion Intranasal administration of NGF attenuates TBI-induced neuroinflamma-tion in rats, which may be associated with its regulatory effect on the Aβ42/NF-κB signaling pathway .

关 键 词：脑外伤 鼻内 投药 炎症反应 神经生长因子 

分 类 号：R651.1[医药卫生—外科学]