胰岛素样生长因子1基因治疗提高老龄大鼠eNOS mRNA和蛋白的表达

Insulin-like growth factor-1 gene therapy improves the levels of mRNA and protein of endothelial nitric oxide synthase in aging related erectile dysfunction in rats

目的 探讨阴茎海绵体内注射胰岛素样生长因子1（ IGF-1）基因能否提高老年性大鼠阴茎勃起功能及其对表皮型一氧化氮合酶（eNOS）表达的影响.方法 实验分为3组,老年组：24月龄SD雄性大鼠20只,按随机数字表法随机又分为2组：PBS对照组和100μg IGF-1质粒注射组,每组10只；青年对照组：4月龄SD雄性大鼠10只.注射后4周行电刺激检测大鼠阴茎海绵体内压（ICP）和平均动脉压（MAP）,分析比较IGF-1基因治疗的效果；RT-PCR和Western印迹检测阴茎海绵体组织中eNOS基因mRNA和蛋白的表达.结果 IGF-1基因治疗后4周,电刺激发现老年PBS对照组ICP/MAP和总ICP明显均低于青年对照组（均P＜0.05）；IGF-1质粒注射组ICP/MAP和总ICP均明显高于PBS对照组（均P＜0.05）,和青年对照组相仿.IGF-1质粒注射组eNOS mRNA和蛋白表达均明显高于PBS对照组（0.62±0.16比0.25±0.08,0.71±0.19比0.27 ±0.09,均P＜0.05）.结论 IGF-1基因治疗能够改善老龄大鼠的勃起功能,同时提高eNOS的含量.

Objective To explore the effects of gene transfer of insulin like growth factor-1 （IGF-1） on the penis of senile rats and the altered levels of mRNA and protein of endothelial nitric oxide synthase （eNOS）.Methods Ten young （4 months） and 20 senile （24 months） Sprague-Dawley male rats were selected.The senile rats were divided into 2 groups： phosphate buffer solution （ PBS）-only （ n =10）and 100 μg IGF-1 plasmid treatment group （n =10）.After a 4-week injection of IGF-1,the responses of intracavernous pressure （ICP） with electrical stimulation to the cavernous nerve and systemic mean arterial pressure （MAP） were evaluated.In the control and transfected senile rats,the levels of eNOS mRNA and protein were examined by reverse transcription-polymerase chain reaction （RT-PCR） and Western blot respectively.Results The ICP/MAP and total ICP were significantly higher in the young control group versus the PBS-only group at Week 4 （P 〈 0.05）.The ICP/MAP and total ICP were significantly higher in the young control group and the 100 μg IGF-1 treatment group versus the PBS-only group at Week 4 （ P 〈0.05）.The levels of mRNA and protein of eNOS were higher in the 100 μg IGF-1 treatment group versus the PBS-only group at Week 4 （0.62 ± 0.16 vs 0.25 ± 0.08,0.71 ± 0.19 vs 0.27 ± 0.09,both P 〈 0.05,respectively）.Conclusion The gene therapy of IGF-1 can ameliorate erectile functions and improve the levels of mRNA and protein of eNOS in senile rats.