摘要
目的:研究胰高血糖素样肽-1(GLP-1)类似物利拉鲁肽对糖尿病(DM)大鼠阴茎海绵体内皮型一氧化氮合酶(e NOS)表达的影响,探讨利拉鲁肽对DM勃起功能障碍(DED)大鼠勃起功能的作用。方法:取6周龄雄性SD大鼠,分为正常对照组(NC,n=10)与实验组(n=20),实验组构建DM大鼠模型,随机将实验组分为DM组(n=8)与GLP-1组(n=8)。干预12周后,检测各组空腹血糖(FPG)、空腹胰岛素(FINS)、甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、睾酮、白介素-6,计算胰岛素敏感指标Homa-IR与Homa-β,比较各组大鼠勃起功能;Western印迹检测各组大鼠阴茎海绵体组织Akt/p-Akt、e NOS/p-e NOS的表达。结果:DM组大鼠勃起次数(0.90±1.14)及勃起率(37.5%)较GLP-1组(2.90±1.53,25.0%)、NC组(4.20±1.05,100%)均明显减少(P<0.05);GLP-1组大鼠勃起率及勃起次数亦少于NC组大鼠(P<0.05)。免疫荧光染色提示e NOS主要表达在海绵体血管、血窦内皮细胞的细胞质中,DM组、GLP-1组e NOS蛋白表达水平显著低于正常对照组(P<0.05),且GLP-1组明显高于DM组(P<0.05)。DM、GLP-1组大鼠阴茎组织e NOS/p-e NOS表达水平较NC组明显下降(P<0.01或0.05)。与DM组相比,GLP-1组大鼠阴茎组织p-e NOS表达水平明显升高(P<0.05)。3组大鼠阴茎组织Akt比较无显著差异(P>0.05)。DM、GLP-1组大鼠阴茎组织p-Akt表达水平较NC组明显下降(P<0.01或0.05)。与DM组相比,GLP-1组大鼠阴茎组织p-e NOS表达水平明显升高(P<0.05)。结论:GLP-1可能通过调节Akt/e NOS信号通路,保护阴茎海绵体组织内皮细胞功能,改善DED大鼠的勃起功能,提示GLP-1的使用可能是将来治疗和预防DED的重要方法之一。
October： To explore the effects of the glucagon-like peptide 1（ GLP-1） liraglutide on the penile erectile function of rats with diabetic erectile dysfunction（ DED） by observing the impact of liraglutide on the expression of e NOS in the corpus cavernosum of diabetic rats. Methods： We randomly divided 30 six-week-old male SD rats into a normal control（ n = 10） and an experimental group（ n = 20）,established models of diabetes mellitus（ DM） in the experimental rats,and subdivided them into a DM（ n = 8）and a GLP-1 group（ n = 8） to receive intramuscular injection of normal saline and liraglutide at 5 mg per kg of the body weight per day,respectively. After 12 weeks of intervention,we obtained the levels of FPG,FINS,TG,TC,HDL-C,LDL-C,testosterone,and IL-6 and the indexes of Homa-IR and Homa-β,detected the expressions of Akt / p-Akt and e NOS / p-e NOS in the corpus cavernosum by Western blot,and compared the erectile function between different groups. Results： The frequency and rate of penile erection were significantly lower in the DM group than in the GLP-1 and normal control groups（ P〈0. 05） and also lower in the GLP-1 group than in the normal controls（ P〈0. 05）. Immunofluorescence staining showed the expression of e NOS mainly in the cytoplasm of the cavernosal vessels and sinusoidal endothelial cells,markedly lower in the DM and GLP-1 groups than in the normal rats（ P〈0. 05）,but higher in the GLP-1 than in the DM group（ P〈0. 05）. The level of e NOS / p-e NOS in the penile tissue was significantly decreased in the DM and GLP-1 groups in comparison with the normal controls（ P〈0. 01 or P〈0. 05）,while that of p-e NOS was markedly increased in the GLP-1 group as compared with the DM group（ P〈0. 05）. No statistically significant differences were observed in the Akt level among the three groups of animals（ P〉0. 05）. The expression of p-Akt was remarkably reduced in the DM and GLP-1 groups in comparison with the control rats（ P〈0. 01 or P〈0. 05）,but higher in the GLP-1 than in the DM group（ P〈0. 05）. Conclusion： GLP-1 can protect the function of endothelial cells in the corpus cavernosum and improve the erectile function of DED rats by regulating the Akt /e NOS signaling pathway,which indicates that GLP-1 could be an important option for the treatment and prevention of DED.
出处
《中华男科学杂志》
CAS
CSCD
北大核心
2016年第3期212-218,共7页
National Journal of Andrology
基金
湖北省自然科学基金(2012FFB06802)~~
