神经生长因子鼻腔给药对有机磷酸酯类化合物中毒大鼠纹状体损伤的影响  

Intranasai dosing of nerve growth factor protects brain from poisoning of organophosphorus compounds in rats

作　　者：樊新颖[1] 李芸[1] 马敏敏[1] 郭芮兵[1] 徐格林[1] 刘新峰[1] 朱武生[1] 

机构地区：[1]南京大学医学院临床学院南京军区南京总医院神经内科,210002

出　　处：《中华医学杂志》2012年第33期2366-2369,共4页National Medical Journal of China

基　　金：国家自然科学基金（31171016）

摘　　要：目的探讨神经生长因子（NGF）经鼻腔给药对有机磷酸酯类化合物（OP）中毒大鼠急性脑损伤的影响和可能机制。方法建立SD大鼠OP中毒模型，常规治疗后进行症状学评分，将评分在2～3分的大鼠按随机数字表法分为阳性对照组和经鼻给予NGF组（n=6），另设正常对照组（n=6）在相应时间点给予生理盐水。中毒24h后采用HE染色观察大鼠纹状体区神经细胞变性、坏死的情况，并测定纹状体区乙酰胆碱酯酶活性、丙二醛和还原型谷胱甘肽含量。结果HE染色发现经鼻给予NGF可以减轻中毒后大鼠纹状体区神经细胞坏死程度。同时中毒后，经鼻给予NGF组和生理盐水组大鼠纹状体区乙酰胆碱酯酶活性均有明显下降[（0．46±0．11）比（0．35±0．09）U／ragprot]，两组间比较差异无统计学意义（P〉0．05）。但是与经鼻给予生理盐水组相比，NGF鼻腔给药的大鼠纹状体区丙二醛含量降低了25．14％[（4．0±0．9）比（5．4±1．3）nmol／mgprot]，还原型谷胱甘肽水平增高了15．73％[（52．8±2．8）比（45．6±4．9）mg／gprot]，两组间差异有统计学意义（P〈0．05）。结论NGF经鼻腔给药可以减轻由OP中毒后大鼠纹状体区损伤程度，其机制可能与对抗自由基损伤及脂质过氧化反应有关。Objective To explore the protective effects of intranasal （IN） dosing of nerve growth factor （NGF） on brain injury induced by organophosphorus compounds （OP） in rats. Methods The OP- treated Sprague-Dawley rats received an intraperitoneal injection of atropine sulphate and pralidoxime at 1 min after intoxication. Then NGF or saline was dosed via the olfactory pathway. All rats were sacrificed 24 hours after OP exposure. Damaged nerve cells were estimated on corpus striatum strained with hematoxylin- eosin （H＆E） method. And the activity of acetylcholinesterase （AchE） and the concentrations of malondialdehyde （MDA） and reduced glutathione hormone （GSH） in corpus striatum were measured by colorimetric method. Results As assessed by H＆E staining, a large number of degenerated and necrotic nerve cells were observed in corpus striatum in rats from in IN saline group. But in IN NGF group, the number of degenerated neurons was smaller than in IN NS group. Following OP exposure, the activity of AchE decreased in corpus striatum in both IN saline and IN NGF groups （0. 46 ± 0. 11 vs 0. 35 ± 0.09 U/rag prot）. No significant differences existed between two groups. But the concentrations of MDA in corpus striatum of IN NGF group rats reduced markedly by 25.14% （4.02±0.85 vs 5.37 ± 1.33 nmol/mg prot） and the level of GSH increased sharply by 15.73% （52.82 ± 2.80 vs 45.64 ± 4.88 mg/g prot） as compared with IN saline group （P 〈 0. 05 ）. Conclusion Intranasal dosing of NGF may improve neuropathology and protect rats against OP-induced oxidative damage in corpus striatum.

关 键 词：有机磷酸酯类化合物 鼻内给药 神经生长因子 脑损伤 

分 类 号：R965[医药卫生—药理学]