鞘内转染重组腺病毒介导人神经生长因子β基因对神经病理性痛大鼠的镇痛作用

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1、•疼痛诊疗与研究•鞘内转染重组腺病毒介导人神经生长因子0基因对神经病理性痛大鼠的镇痛作用王清秀彭成为杨镭镭施静姚尚龙【摘要】目的评价鞘内转染重组腺病毒介导人神经生长因子p(Ad-hNGF^)基因对神经病理性痛大鼠的镇痛作用。方法雄性SD大鼠96只，体畫200~250g,随机分为3组(n=32),假手术组(1组)假手术后立即鞘内注射人工脑脊液；II组和ID组制备坐骨神经慢性压迫性损伤(CCI)模型，术后分别立即鞘内注射人工脑脊液或Ad・hNG邛基因。分别于术前1d(基础值)和转染后4~28d每4天测定整体行为学评分、机械痛阈和热痛阈；每组分别于

2、转染后4.7.14及28d各处死8只大鼠，取脊關组织，每个时点的4个标本用于测定hNGF?表达(免疫组化方法)，每个时点的另外4个标本用于测定hNGFR的含駅(ELISA法)。结果DI组脊髓出现hNGF?表达；HI组脊101hNGFp含晟高于1组和II组(P<0.01);与1组比较，II组和01组行为学评分升高，机械痛阈及热痛阈均降低(P<0.05或0.01);与II组比较，DI组行为学评分及机械痛阈差异无统计学意义(P>0.05),转染后8~24d热痛闹升高(PvO.05)。结论CCI诱导的慢性神经病理性痛大鼠梢内转染Ad-hNGFp基因后

3、，可在脊髓组织持续、高效表达，且能减轻热痛觉过敏，但对机械痛觉过敏无影响。【关律词】神经生长因子,注射，脊能;转染；神经痛Analgesiceffectofintrathecaltransfectionofhumanbeta-nervegrowthfactorgeneinaratmodelofneuropathicpainWANGQing-xiu9PENGCheng-wei,YANGZzdZei,etal・DepartmentofAnesthesiology,People'sHospital9YunyangMedicalCollege,Shi

4、yan442000>HubeiProvince,China[Abstract]ObjectiveToexaminetheanalgesiceffectofintrathecal(IT)adenoviruscontaininghumanbeta*nervegrowth卩factor(Ad-hNGFp)geneinaratmodelofneuropathicpaininducedbychronicconstrictiveinjury(CCI)・MethodsNinety-sixmaleSDratsweighing200-250gwererando

5、mlydividedinto3groups(n=32each):groupIshamoperation;groupQCCIandgroupDICCI+Ad・hNGFpgeneIT.Theanimalswereanesthetizedwithintraperitonealchloralhydrate300-350mg/kg•"Hierightsciaticnervewasexposedand4ligatureswereplacedonthesciaticnerveat1-2mmintervalsasdescribedbyBennetandXie

6、・Inshamoperationgrouprightsciaticnervewasexposedbutnotligated.Ingroup1andUartificialcerebro-spinalfluidwasinjectedintvavenouslyinsteadofAd-hNGF^gene.Hiebehaviorscoreandthepaw-withdrawallatency(PWL)toradiantheatandmechanicalstimulusweremeasuredonedaybeforeandevery4daysaftero

7、peration.Eightanimalswerekilledat417f14and28dayafterITgenetransfectionineachgroupandlumbarsegment(1^4)ofthespinalcordwasremovedfordeterminationofhNGFpexpression(byimmunohistochemistry)andhNGF0content(byEUSA)・ResultsTherecombinantAd-hNGFpcontentofthespinalcordwassignificantl

8、yhigheringroupIDthaningroupIandU•l^iebehaviorscoresweresignificantlyhigherandPWLto