摘要
目的观察L-精氨酸(L-Arg)对糖尿病大鼠阴茎勃起功能障碍(ED)的疗效,并探讨其作用机制。方法用高脂饲养加小剂量链脲佐菌素腹腔注射制备糖尿病大鼠模型,经L-Arg灌胃治疗8周后,检测离体海绵体对乙酰胆碱(ACh)的舒张反应;ELISA法检测海绵体一氧化氮合酶(NOS)抑制物非对称性二甲基精氨酸(ADMA)和cGMP含量,检测超氧化物歧化酶活性和脂质过氧化产物丙二醛含量以反映氧化应激。结果与正常对照组比较,糖尿病大鼠海绵体对ACh舒张反应明显降低,提示阴茎勃起功能障碍;海绵体ADMA蓄积,NOS活性抑制, NO和cGMP含量减少;氧化应激增加;L-Arg灌胃治疗8周能逆转以上指标,用L-Arg体外孵育糖尿病大鼠海绵体也能改善其舒张功能障碍。结论海绵体ADMA蓄积及其信号通路紊乱是导致糖尿病大鼠ED的重要原因。L-Arg治疗可改善糖尿病大鼠海绵体舒张功能障碍,其机制与增加NO含量和改善氧化应激有关。
Aim To investigate the therapeutic effect of L-arginine on penile erectile dysfunction in diabetic rats and its underlying mechanism.Methods Type 2 diabetic rats were induced by high-fat diet plus intraperitoneal injection of small dose streptozotocin(STZ,30 mg·kg^-1)as a bolus.After the successful establishment of diabetic model,half of rats were treated with L-arginine(100 mg·kg^-1·d^-1,i.g.)for eight weeks.By the end of the experiment,corpora cavernosa were isolated from rats under anesthesia for the examination of relaxation function response to acetylcholine(ACh)to reflect erectile function.Contents of nitric oxide synthase(NOS)inhibitor asymmetric dimethylarginine(ADMA)and cGMP were measured by ELISA in cavernosal tissue.NOS activity and nitric oxide(NO)content were determined by colorimetric method.The activity of the antioxidative enzyme superoxide dismutase(SOD)and content of the lipid peroxidative production malondialdehyde(MDA)were analyzed to reflect oxidative stress.Results The relaxation response to ACh of corpus cavernosum in diabetic rats was significantly lower than that of control rats,indicating penile erectile dysfunction in diabetic rats.In comparison with control rats,accumulated endogenous NOS inhibitor ADMA,inhibited NOS activity,decreased NO and cGMP contents were observed in the corpus cavernosum of diabetic rats accompanied with an increase of oxidative stress.Treatment with L-arginine in vivo for eight weeks could reverse the above changes in diabetic rats,and in vitro incubation of isolated corpus cavernosum from diabetic rats with L-arginine(10μmol·L^-1)for 45 min could also improve the impairment of relaxation function responses to ACh.Conclusion The erectile dysfunction of corpus cavernosum in diabetic rats is related to the accumulation of endogenous NOS inhibitor ADMA and disorder of its signaling pathway.Treatment with L-arginine both in vivo and in vitro could ameliorate the relaxation dysfunction of corpus cavernosum in diabetic rats,and the underlying mechanisms are associated with increase of NO availability and suppression of oxidative stress.
作者
黄程
雷艳萍
李晓媚
杨文豪
熊燕
HUANG Cheng;LEI Yan-ping;LI Xiao-mei;YANG Wen-hao;XIONG Yan(Guangzhou Institute of Snake Venom Research,School of Pharmaceutical Sciences,Guangzhou Medical University,Guangzhou 511436,China)
出处
《中国药理学通报》
CAS
CSCD
北大核心
2018年第11期1521-1527,共7页
Chinese Pharmacological Bulletin
基金
广州市科技计划资助项目(No 2014J4100067)
国家自然科学基金面上项目(No 81570751)。
