CAJ | 학술논문

目的探讨皮下转染重组腺病毒介导的人神经生长因子β(Ad-hNGFβ)基因对糖尿病大鼠神经病理性痛的影响及其可能机制.方法采用腹腔注射佐脲霉菌素(STZ)75 mg/kg的方法制备大鼠糖尿病模型.健康雄性SD大鼠,体重180～220 g,随机取10只大鼠作为对照组(C组)不制备糖尿病模型;取模型制备成功的大鼠75只随机分为3组(n=25):糖尿病神经病理性痛组(DNP组)、Ad-hNGFβ基因治疗组(NGF组)和Ad-LacZ基因治疗组(LacZ组).NGF组和LacZ组分别于STZ注射后21d且痛阈测定结束后双侧腹股沟皮下脂肪接种1.12×1011 PFU Ad-hNGFβ 10 μl和1.12 x 1011 PFUAd-LacZ 10 μl,C组和DNP组不作任何处理.于STZ注射前(基础状态)、注射后21、35、49 d时测定机械痛阈和热痛阈.于注射后49 d且痛阈测定结束后测定血清hNGFβ浓度和背根神经节降钙素基因相关肽(CGRP)的表达.结果与基础值和C组比较,DNP组、NGF组和LacZ组STZ注射后机械痛阈和热痛阚均降低.DNP组和LacZ组血清hNGFβ浓度和背根神经节CGRP表达下降,NGF组血清hNGFβ浓度和背根神经节CGRP表达升高(P＜0.05);与DPN组比较,NGF组STZ注射后49 d时热痛阈升高,血清hNGFβ浓度和背根神经节CGRP表达升高(P＜0.01),LacZ组各项指标差异无统计学意义(P＞0.05).结论 Ad-hNGFβ基因转染可在一定程度上减轻糖尿病大鼠神经病理性痛,其机制与上调背根神经节CGRP表达有关.
목적 탐토피하전염중조선병독개도적인신경생장인자β(Ad-hNGFβ)기인대당뇨병대서신경병이성통적영향급기가능궤제.방법 채용복강주사좌뇨매균소(STZ)75 mg/kg적방법제비대서당뇨병모형.건강웅성SD대서,체중180～220 g,수궤취10지대서작위대조조(C조)불제비당뇨병모형;취모형제비성공적대서75지수궤분위3조(n=25):당뇨병신경병이성통조(DNP조)、Ad-hNGFβ기인치료조(NGF조)화Ad-LacZ기인치료조(LacZ조).NGF조화LacZ조분별우STZ주사후21d차통역측정결속후쌍측복고구피하지방접충1.12×1011 PFU Ad-hNGFβ 10 μl화1.12 x 1011 PFUAd-LacZ 10 μl,C조화DNP조불작임하처리.우STZ주사전(기출상태)、주사후21、35、49 d시측정궤계통역화열통역.우주사후49 d차통역측정결속후측정혈청hNGFβ농도화배근신경절강개소기인상관태(CGRP)적표체.결과 여기출치화C조비교,DNP조、NGF조화LacZ조STZ주사후궤계통역화열통감균강저.DNP조화LacZ조혈청hNGFβ농도화배근신경절CGRP표체하강,NGF조혈청hNGFβ농도화배근신경절CGRP표체승고(P＜0.05);여DPN조비교,NGF조STZ주사후49 d시열통역승고,혈청hNGFβ농도화배근신경절CGRP표체승고(P＜0.01),LacZ조각항지표차이무통계학의의(P＞0.05).결론 Ad-hNGFβ기인전염가재일정정도상감경당뇨병대서신경병이성통,기궤제여상조배근신경절CGRP표체유관.
Objective To investigate the effects of subcutaneous transfection of human beta-nerve growth factor(Ad-hNGFβ)gene on diabetic neuropathic pain(DNP)in rats and the mechanism.Methods Male SD rats weishing 180-220 g were used in this study.Ten rats were randomly collected as normal control without DNP.DNP model Wng made by intraperitoneal injection of streptuzocin(STZ)75 mg/kg.Seventy-five rats with DNP were randomly divided into 3 groups(n=25 each):group Ⅰ DNP;group Ⅱ NGF and group Ⅲ LacZ.Group NGF and group LacZ received subcutaneous transfecfion of 1.12×1011 PFU Ad-hNGFβ 10μl and 1.12 × 1011 PFU Ad-LacZ 10 μl respectively after pain threshold was measured on 21 d after STZ injection.Results The mechanical and thermal pain threshold,serum concentration of hNGFβ and dorsal root ganglion CGRP expression were significantly lower in DNP group than in control group(P＜0.05)and were significandy higher in NGF group than in DNP group(P＜0.01).There was no significant difference in all the indexes between group LacZ and control group.Conclusion Subcutaneous transfection of Ad-hNGFβ can attenuate DNP to some extent and CGRP in dorsal root ganglion may be involved in the mechanism.