摘要
目的探讨增龄对大鼠阴茎组织中DDAH2/ADMA/eNOS通路的影响。方法以18月龄和3月龄雄性大鼠分别作为老年组和青年组。测定两组大鼠阴茎海绵体内压(intracavernous pressure,ICP)及海绵体内注射罂粟碱后的ICP,采集阴茎组织,应用电镜比较两组大鼠阴茎海绵体细胞显微结构的差别,应用ELISA测定两组大鼠阴茎组织中环磷酸鸟苷(cyclic guanosine monophosphate,cGMP)、不对称二甲基精氨酸(asymmetrical dimethylarginine,ADMA)含量,应用Western blot比较两组阴茎组织中内皮型一氧化氮合酶(endothelial nitric oxide synthase,eNOS)、二甲基精氨酸二甲胺水解酶2(dimethylarginine dimethylaminohydrolases 2,DDAH2)的差别。结果老年组基础ICP(9.84±1.63mmHg)与青年组(10.66±1.66mmHg)比较差异无统计学意义(P>0.05),注射罂粟碱后老年组ICP(33.46±5.37mmHg)明显低于青年组(39.71±3.67mmHg)(P<0.05)。电镜下老年组大鼠阴茎海绵体细胞与青年组相比纤维化明显,内皮细胞内线粒体肿胀、聚集、空泡化明显,线粒体、内质网等细胞器明显减少,核膜变形、染色质异常时见。ELISA检测老年组大鼠阴茎组织中cGMP浓度178.87±19.53pmol/g明显低于青年组268.67±25.28pmol/g(P<0.05),而老年组ADMA浓度61.04±4.19μmol/g明显高于青年组42.85±4.09μmol/g(P<0.01)。Western blot法检测老年组阴茎组织中eNOS、DDAH2表达均明显低于青年组。结论 DDAH2/ADMA/eNOS通路的改变可能是导致老年性阴茎勃起功能障碍(erectile dysfunction,ED)的重要原因。
Objective To investigate the effects of aging on DDAH2/ADMA/eNOS pathway in penile tissue.Methods Ten male SD rats of 3 months and 10 male SD rats of 18 months were assigned respectively to the young group and the aged group.Intracavernous pressure (ICP) was measured before and after hydrochloride papaverine injection.Penile tissue was sliced and observed under transmission electron microscope.The rest was collected and preserved.Cyclic guanosine monophosphate(cGMP) and asymmetrical dimethylarginine (ADMA) of penile tissue were detected by ELISA.Expression of endothelial nitric oxide synthase(eNOS) and dimethylarginine dimethy laminohydrolases 2 (DDAH2) were measured by western blot.Results There was no difference between aged group and young group in the baseline level of ICP (9.84 ± 1.63 vs 10.66 ± 1.66mmHg,P > 0.05).Significant difference between aged group and young group was found in papaverine induced ICP(33.46 ± 5.37 vs 39.71 ± 3.67mmHg,P < 0.05).Under the electron microscope,the fibration was evident in aged penile tissue.The mitochondria of the endothelial cells was concentrated,swollen,cavitated,and the organelles decreased significantly in aged penile tissue.The karyon of the endothelial cells was deformed with sporadical abnormalities of chromatin in aged penile tissue.Compared with young group,the A DMA increased(61.04 ± 4.19 vs 42.85 ± 4.09μmol/g,P < 0.01) while the concentration of cGMP (178.87 ± 19.53 vs 268.67 ± 25.28pmol/g,P <0.05) and the expression of eNOS and DDAH2 decreased significantly in aged penile tissue.Conclusion The changes of DDAH2/ADMA/eNOS pathway might play a key role in age-related ED.
出处
《医学研究杂志》
2014年第9期40-44,共5页
Journal of Medical Research
基金
山东省科技攻关计划基金资助项目(2007GG2N02074)