CAJ | 학술논문

目的评价皮下转染重组腺病毒介导的人神经生长因子β(Ad-hNGFβ)基因对糖尿病神经病理性痛大鼠背根神经节P物质表达的影响.方法健康雄性SD大鼠,体重180 ～ 220 g,采用腹腔注射链脲霉素(STZ) 75 mg/kg的方法制备大鼠糖尿病模型.取10只大鼠作为对照组(C组),不制备糖尿病模型；取75只糖尿病模型制备成功的大鼠,采用随机数字表法,将其随机分为3组(n=25):糖尿病神经病理性痛组(DNP组)、Ad-hNGFβ基因治疗组(Ad-NGF组)和LacZ重组复制缺陷性腺病毒基因治疗组(Ad-LacZ组).Ad-NGF组和Ad-LacZ组分别于STZ注射后21 d且痛阈测定结束后双侧腹股沟皮下脂肪接种1.12× 1010 PFU Ad-hNGFβ 10μl和1.12× 1010 PFU Ad-LacZ 10μl.分别于STZ注射前、注射后21、35和49d时测定机械痛阈和热痛阈.于注射后49d时痛阈测定结束后采用免疫组化法测定背根神经节P物质的表达.结果与C组比较,DNP组、Ad-NGF组和Ad-LacZ组注射后各时点机械痛阈和热痛阈降低,DNP组和Ad-LacZ组背根神经节P物质表达下调(P＜0.05)；与DNP组比较,Ad-NGF组注射后49d时热痛阈升高,背根神经节P物质表达上调(P＜0.01),Ad-LacZ组各时点机械痛阈、热痛阈和背根神经节P物质表达差异无统计学意义(P＞0.05).结论 Ad-hNGF基因转染可能通过上调背根神经节P物质的表达在一定程度上减轻糖尿病大鼠神经病理性痛.
목적 평개피하전염중조선병독개도적인신경생장인자β(Ad-hNGFβ)기인대당뇨병신경병이성통대서배근신경절P물질표체적영향.방법 건강웅성SD대서,체중180 ～ 220 g,채용복강주사련뇨매소(STZ) 75 mg/kg적방법제비대서당뇨병모형.취10지대서작위대조조(C조),불제비당뇨병모형；취75지당뇨병모형제비성공적대서,채용수궤수자표법,장기수궤분위3조(n=25):당뇨병신경병이성통조(DNP조)、Ad-hNGFβ기인치료조(Ad-NGF조)화LacZ중조복제결함성선병독기인치료조(Ad-LacZ조).Ad-NGF조화Ad-LacZ조분별우STZ주사후21 d차통역측정결속후쌍측복고구피하지방접충1.12× 1010 PFU Ad-hNGFβ 10μl화1.12× 1010 PFU Ad-LacZ 10μl.분별우STZ주사전、주사후21、35화49d시측정궤계통역화열통역.우주사후49d시통역측정결속후채용면역조화법측정배근신경절P물질적표체.결과 여C조비교,DNP조、Ad-NGF조화Ad-LacZ조주사후각시점궤계통역화열통역강저,DNP조화Ad-LacZ조배근신경절P물질표체하조(P＜0.05)；여DNP조비교,Ad-NGF조주사후49d시열통역승고,배근신경절P물질표체상조(P＜0.01),Ad-LacZ조각시점궤계통역、열통역화배근신경절P물질표체차이무통계학의의(P＞0.05).결론 Ad-hNGF기인전염가능통과상조배근신경절P물질적표체재일정정도상감경당뇨병대서신경병이성통.
Objective To investigate the effects of subcutaneous transfection of human beta-nerve growth factor (Ad-hNGFβ) gene on the expression of substance P (SP) in the dorsal root ganglion in a rat model of diabetic neuropathic pain (DNP).Methods Male SD rats weighing 180-220 g were used in this study.Ten rats were randomly collected as normal control without DNP (group C).DNP model was made by intraperitoneal injection of streptozocin (STZ) 75 mg/kg.Seventy-five rats with DNP were randomly divided into 3 groups ( n =25 each):DNP group; Ad-hNGF group and Ad-LacZ group.Groups Ad-NGF and Ad-LacZ received subcutaneous transfection of 1.12 × 1010 PFU Ad-hNGFβ 10 μl and 1.12 × 1010 PFU Ad-LacZ 10 μl respectively after pain threshold was measured on 21d after STZ injection.The mechanical and thermal pain threshold was measured before STZ injection (baseline) and at 21,35 and 49 d after STZ injection.The expression of SP in the dorsal root ganglion was determined after the measurement of pain threshold on 49 d after STZ injection.Results Compared with group C,the mechanical and thermal pain threshold was significantly decreased at each time point after STZ injection in groups DNP,Ad-NGF and Ad-LacZ,and the expression of SP in the dorsal root ganglion was signilicantly downregulated in groups DNP and Ad-LacZ (P ＜ 0.05).Compared with group DNP,the thermal pain threshold was significantly increased on 49 d afar STZ injection,and the expression of SP in the dorsal root ganglion was significantly up-regulated in group Ad-NGF ( P ＜ 0.01 ),and no significant change was found in the mechanical and thermal pain threshold and the expression of SP in the dorsal root ganglion at each time point in group Ad-LacZ ( P ＞ 0.05).Conclusion Subcutaneous transfection of Ad-hNGFβ can attenuate DNP to some extent through upregulation of the expression of SP in rat dorsal root ganglion.