人神经生长因子β基因转染对糖尿病大鼠周围神经病变的影响

Effects of Human Nerve Growth Factor β Gene Transfection on Diabetic Peripheral Neuropathy in Rats

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)基因对糖尿病大鼠周围神经病变的影响及其作用机制。方法:75只糖尿病大鼠随机分为3组:糖尿病组(DM组)、Ad-hNGFβ组、Ad-LacZ组,另取10只健康雄性SD大鼠作为对照组(C组)。STZ注射后21 d,Ad-hNGFβ组和Ad-LacZ组分别皮下注射Ad-hNGFβ和Ad-LacZ,C组和DM组皮下注射相同剂量的生理盐水。分别于STZ注射前、注射后21、35和49 d测定热痛阈,49 d测定感觉神经传导速度和潜伏期及血清hNGFβ浓度。结果:与C组比较,DM组在STZ注射后21 d热痛阈明显降低(P<0.05),持续到49 d,且血清hNGFβ浓度明显下降(P<0.01),感觉神经传导速度减慢(P<0.01),潜伏期明显延长(P<0.01);与DM组相比,STZ注射后49 d,Ad-hNGFβ组热痛阈明显升高(P<0.05),血清hNGFβ浓度升高(P<0.01)、感觉神经传导速度及潜伏期有所恢复(P<0.05);Ad-LacZ组各项指标与DM组比较无明显改变。结论:Ad-hNGFβ基因转染可缓解大鼠糖尿病神经性病变,此作用可能与Ad-hNGFβ基因高表达有关。

Objective To investigate the effect of adenovirus-mediated human nerve growth factor βgene（Ad-hNGFβ gene） subcutaneously transfection on diabetic peripheral neuropathy in rats and its possible mechanism.Methods Seventy-five diabetic rats were randomly divided into diabetes mellitus group（DM group）,Ad-hNGFβ group,Ad-LacZ group and another healthy rats were selected as controls（C group）.After administrating with streptozocin（STZ） for 21 d,Ad-hNGFβ group and Ad-LacZ group were subcutaneouly injected with Ad-hNGFβ and Ad-LacZ,respectively.C group and DM group were given the same dose of normal saline.The threshold of heat pain were measured before STZ injection,and 21,35,49 d after injection,respectively.The sensory nerve conduction velocity（SNCV）,latency period and serum concentration of hNGFβ were measured at 49 d.Results Compared with C group,the threshold of heat pain in DM group was significantly decreased at 21 d and last till 49 d after STZ injection（P0.05）,meanwhile serum concentration of hNGFβ and SNCV were all significantly decreased（allP 0.01）,but the latency period was significantly prolonged（P0.01）;compared with DM group,the threshold of heat pain in Ad-hNGFβ group was significantly increased at 49 d after STZ injection（P0.05）,the serum concentration of hNGFβ was significantly increased（P0.01）,SNCV and latency period were improved significantly（P0.05）;all the indexes of Ad-LacZ group had no significant difference with DM group.Conclusion Ad-hNGFβ gene transfection could alleviate the symptom of rats with diabetic peripheral neuropathy,which may be related with the high expression of Ad-hNGFβ gene.