外源性一氧化氮合酶抑制物L-NNA对大鼠勃起功能的影响  

Effect of nitric oxide synthase inhibitor N^ω-Nitro-L-arginine on the penile erectile function of healthy male rats

作　　者：黄程 谭茵 雷艳萍 李晓媚 熊燕 

机构地区：[1]广州医科大学药学院,广州蛇毒研究所,广州511436 [2]中山大学附属第三医院粤东医院药剂科,广东省梅州514000

出　　处：《中国医师杂志》2017年第10期1456-1461,共6页Journal of Chinese Physician

基　　金：国家自然科学基金（81570751）;广州市科技计划资助项目（2014J4100067）

摘　　要：目的前期研究揭示内源性一氧化氮合酶（NOS）抑制物与糖尿病大鼠阴茎勃起功能障碍（ED）密切相关，本研究拟观测外源性NOS抑制物N’-硝基-L-精氨酸（L—NNA）对正常大鼠阴茎勃起功能的直接影响。方法给雄性SD大鼠灌胃L—NNA（50mg／kg）16周诱导高NOS抑制物大鼠模型；麻醉下分离大鼠阴茎海绵体置器官浴槽并检测乙酰胆碱（ACh）诱导的舒张反应以反映其勃起功能；用ELISA检测海绵体环一磷酸鸟苷（cGMP）含量，用比色法检测NOS活性与一氧化氮（NO）含量，检测抗氧化酶SOD活性和脂质过氧化产物丙二醛（MDA）含量以反映氧化应激，用Western blotting检测NOS与磷酸二酯酶5（PDE5）蛋白表达。结果与正常对照组比较，L-NNA模型大鼠海绵体对ACh的舒张反应明显降低，提示阴茎勃起功能障碍；并伴有海绵体组织NO和cGMP含量显著减少，NOS活性抑制，海绵体内皮型一氧化氮合酶（eNOS）和神经型一氧化氮合酶（nNOS）表达下调，而诱导型一氧化氮合酶（iNOS）和PDE5蛋白表达上调，氧化应激增加；用1-10μmol／L的L—NNA体外孵育正常大鼠海绵体30min亦可呈剂量依赖性地抑制其舒张功能，而用3mmoL／L的L-精氨酸体外孵育45min可改善L—NNA体内、体外所致的大鼠海绵体舒张功能障碍。结论外源性NOS抑制物L—NNA对大鼠海阴茎勃起功能具有直接的抑制作用，其机制与减少NO含量和增加氧化应激有关。Ojective To investigate the direct effect of exogenous NOS inhibitor N^ω-Nitro-L-arginine （L-NNA） on the erectile function of healthy male rats in order to clarify the mechanism of the erectile dysfunction of type 2 diabetic rats. Methods L-NNA （50 mg/kg） was administered by oral gavage to Sprague Daw｜ey （SD） rats for 16 weeks to induce rat model of NOS inhibition. By the end of the experi- ment, corpora cavernosa was isolated from the rats under anesthetization and fixed in an organ chamber for the examination of relaxation function response to acetylcholine （ACh） to reflect erectile function. Enzyme-linked immunosorbent assay （ELISA） was performed to determine the content of cyclic guanosine mono- phosphate （cGMP） in cavernosal tissue. NOS activity and nitric oxide （NO） content were measured by col- orimetric method. Western blotting was employed to detect the protein expression of NOS and phosphodies- terase 5 （ PDE5 ）. The activity of the antioxidative enzyme superoxide dismutase （SOD） and content of the lipid peroxidative product malondialdehyde （MDA） were analyzed to reflect oxidative stress. Results In comparison with control group, the relaxation response to acetylcholine of corpus cavernosum was significanfly impaired in L-NNA model rats, indicating penile erectile dysfunction. Either decreased contents of NO and cGMP or suppressed activity of NOS were observed in the corpus cavernosum of L-NNA model rats and in accompany with the down-regulation of endothelial NOS （eNOS） and neuronal NOS （nNOS） expression, up-regulation of inducible NOS （iNOS） and PDE.5 expression as well as an increase of oxidative stress. In- cubation of corpus cavernosum from control rats with L-NNA （ 1-10 I-mol/L） ex vivo for 30 min could also inhibit the relaxation function responses to acetylcholine in a dose-dependent manner. Treatment with L-ar- ginine ex vivo for 45 min could improve the impairments of relaxation function responses to acetylcholine of corpus cavernosum

关 键 词：N'硝基-L.精氨酸 海绵体 勃起功能 一氧化氮 氧化应激 

分 类 号：R698[医药卫生—泌尿科学]