PI3K/Akt/eNOS通路介导山药蛋白对肾阳虚大鼠阴茎勃起功能障碍的改善作用

PI3K/Akt/eNOS pathway mediated the amelioration effect of Chinese yam protein on penile erectile dysfunction in kidney-yang deficiency rats

目的:探讨山药蛋白(DP1)对肾阳虚大鼠阴茎勃起功能障碍(erectile dysfunction,ED)的改善作用及机制。方法:建立氢化可的松诱导的肾阳虚大鼠模型,分成对照组、模型组、DP1低剂量组(0.6 mg·kg-1)、DP1高剂量组(0.9 mg·kg-1)。检测大鼠体质量变化;采用ELISA法检测促性腺激素释放激素(GnRH)、促黄体生成素(LH)和睾酮(T)含量;通过皮下注射阿扑吗啡测定大鼠阴茎勃起次数和勃起率;以苏木素-伊红染色观察阴茎海绵体组织形态;采用Western blot检测勃起关键信号通路蛋白表达水平、ELISA测定一氧化氮(NO)和环磷酸鸟苷(cGMP)含量,探索DP1改善肾阳虚大鼠ED的机制。结果:与模型组相比,DP1组大鼠体质量显著增加;GnRH、LH和T含量升高;阴茎勃起次数及勃起率显著提高;海绵体组织形态完整性恢复。DP1的干预能够增加磷脂酰肌醇3激酶(PI3K)、蛋白激酶B(Akt)以及内皮型一氧化氮合酶(eNOS)蛋白磷酸化水平,显著提高NO和cGMP含量。结论:DP1能够改善肾阳虚大鼠ED,且与激活PI3K/Akt/eNOS信号通路相关。

OBJECTIVE To explore the amelioration effect and mechanism of Chinese yam protein(DP1)on penile erectile dysfunction(ED)in kidney-yang deficiency rats.METHODS The rats were divided into control group,model group,DP1 low-dose group(0.6 mg·kg-1)and DP1 high-dose group(0.9 mg·kg-1),and the kidney-yang deficiency rat model was established by hydrocortisone.The changes of body weight of rats were detected.The contents of gonadotropin releasing hormone(GnRH),luteinizing hormone(LH)and testosterone(T)were measured by ELISA.The number and rate of penile erection in rats were determined by subcutaneous injection of apomorphine.Histomorphology of corpus cavernosum tissue was observed by hematoxylin-eosin staining.To explore the mechanism of DP1 ameliorating ED in kidney-yang deficiency rats,Western blot was used to detect the expression level of erectile critical signaling pathway proteins,and ELISA was used to determine the contents of nitric oxide(NO)and cyclic guanosine phosphate(cGMP).RESULTS Compared with the model group,the body weight,the contents of GnRH,LH and T,the number and rate of penile erections of DP1 group were significantly increased.The morphological integrity of the corpus cavernosum tissue was recovered.The intervention of DP1 could significantly increase the phosphorylation levels of phosphatidylinositol 3 kinase(PI3 K),protein kinase B(Akt),and endothelial nitric oxide synthase(eNOS)and enhance NO and cGMP contents.CONCLUSION DP1 could improve ED in rats with kidney-yang deficiency and was associated with activation of PI3 K/Akt/eNOS signaling pathway.