“起痿3号”联合西地那非对糖尿病勃起功能障碍大鼠阴茎海绵体组织Rho激酶活性及AKT/eNOS通路的影响研究  

Qiwei No.3 combined with sildenafil inhibits Rho kinase activity and increases AKT/eNOS expressions in the penile cavernosum of rats with diabetic erectile dysfunction

作　　者：赵伟 李琳 张莉 张晓庆 李东旭 夏靖 ZHAO Wei;LI Lin;ZHANG Li;ZHAO Xiao-qing;LI Dong-xu;XIA Jing(Department of Andrology,Yangzhou Traditional Chinese Medicine Hospital,Yangzhou,Jiangsu 225000,China;School of Traditional Chinese Medicine,Beijing University of Chinese Medicine,Beijing 100029,China)

机构地区：[1]扬州市中医院男科,江苏扬州225000 [2]北京中医药大学中医学院,北京100029

出　　处：《中华男科学杂志》2024年第12期1128-1134,共7页National Journal of Andrology

基　　金：江苏省中医药科技发展计划项目(YB2020084)。

摘　　要：目的:探讨“起痿3号”联合西地那非对糖尿病勃起功能障碍(DED)大鼠阴茎海绵体组织Rho激酶活性及AKT/eNOS通路的影响。方法:用链脲佐菌素溶液腹腔注射SD雄性大鼠,成功造模糖尿病大鼠。饲养8周后,大鼠颈部注射阿扑吗啡,制备DED大鼠模型。将24只造模成功的大鼠随机分为模型对照组(MC组)、西地那非组[5 mg/(kg·d)](S组)、“起痿3号”低剂量[10 g/(kg·d)]+西地那非组[5 mg/(kg·d)](LQ+S组)及“起痿3号”高剂量[20 g/(kg·d)]+西地那非组[5 mg/(kg·d)](HQ+S组),每组6只,另配置6只空白对照组大鼠(BC组),BC组和MC组给予等量生理盐水,余组大鼠连续给药6周。颈部注射阿扑吗啡观察5组大鼠的勃起次数,通过Western印迹检测大鼠阴茎海绵体组织Rho激酶活性及p-AKT、eNOS的蛋白表达水平。结果:与BC组比较,所有造模后的大鼠血糖均升高,体质量降低,提示造模成功。与MC组对比,S组、LQ+S组及HQ+S组大鼠模型的勃起次数显著增多,差异具有统计学意义(P<0.05)。HQ+S组大鼠勃起次数多于S组大鼠勃起次数,差异具有统计学意义(P<0.05)。与BC组对比,MC组大鼠阴茎海绵体中的Rho-GTP激酶活性表达水平显著提高(P<0.05);HQ+S组大鼠阴茎海绵体中的Rho-GTP激酶活性表达水平显著低于S组(P<0.05)。各组大鼠阴茎海绵体中的p-AKT蛋白表达水平无明显差异(P>0.05)。与MC组对比,BC组、HQ+S组大鼠阴茎海绵体中的eNOS蛋白表达水平显著升高(P<0.05);HQ+S组大鼠阴茎海绵体中的eNOS蛋白表达水平显著高于LQ+S组与S组(P<0.05)。结论:高剂量“起痿3号”联合西地那非能够改善DED大鼠勃起功能,其机制可能与通过抑制Rho-GTP激酶活性和增加e-NOS通路蛋白表达以释放更多NO有关。Objective:To explore the effects of Qiwei No.3 combined with sildenafil on Rho kinase activity and AKT/eNOS pathways in the penile cavernous tissue of male rats with diabetic erectile dysfunction(DED).Methods:We constructed a model of DED in 24 SD male rats by intraperitoneal injection of streptozotocin solution and injecting apomorphine into the neck after 8 weeks of feeding,equally randomized the model rats into a model control(MC),a sildenafil(S),a low-dose Qiwei No.3 combined with sildenafil(LQ+S)and a high-dose Qiwei No.3 combined with sildenafil(HQ+S)group,and took another 6 normal male rats as blank controls(BC).We treated intragastrically the animals in the BC and MC groups with normal saline,and those in the S,LQ+S and HQ+S groups with sildenafil(5 mg/kg/d),Qiwei No.3(10 g/kg/d)+sildenafil(5mg/kg/d),and Qiwei No.3(20g/kg/d)+sildenafil(5mg/kg/d),respectively.After 6 weeks of treatment,we recorded the number of penile erections of all the rats by injecting apomorphine into the neck,and measured the activity of Rho kinase and expressions of p-AKT and eNOS proteins in the corpus cavernosum by Western blot.Results:Compared with the blank controls,all the DED model rats showed evidently elevated blood glucose and reduced body weight.The number of penile erections was significantly increased in the S,LQ+S and HQ+S groups in comparison with that in the model controls(P<0.05),even higher in the HQ+S than in the S group(P<0.05).The activity of Rho kinase in the penile cavernosum was significantly higher in the MC than in the BC group(P<0.05),but lower in the HQ+S than in the S group(P<0.05).No statistically significant difference was observed in the expression level of the p-AKT protein in the penile cavernosum among the five groups of rats(P>0.05).The expression of eNOS was remarkably up-regulated in the BC and HQ+S groups(P<0.05)compared with that in the MC group,even more significantly in the HQ+S than in the LQ+S and S groups(P<0.05).Conclusion:The combination of high-dose"Qiwei No.3"and sildenafil can improve

关 键 词：糖尿病勃起功能障碍 “起痿3号” RHO激酶 AKT通路 eNOS通路 

分 类 号：R698.1[医药卫生—泌尿科学]