疏肝益阳胶囊对动脉性勃起功能障碍大鼠VEGF、IGF及Akt1激酶表达的影响

Shugan Yiyang capsule increases the expressions of VEGF,IGF and Akt1 in the rat model of arteriogenic erectile dysfunction

目的:血管内皮生长因子(VEGF)、胰岛素样生长因子(IGF)等在维持血管内皮功能中起到重要的作用,蛋白激酶B(Akt1)是细胞内信号转导通路的重要分子。本研究通过检测动脉性勃起功能障碍(AED)大鼠VEGF、IGF及Akt1激酶表达和磷酸化,探讨中药疏肝益阳胶囊治疗AED的分子机制。方法:选取3月龄成年雄性SD大鼠60只,采用双侧髂内动脉结扎法制造阴茎勃起障碍模型。设假手术对照组、模型组、西地那非组[10.5 mg/(kg.d)]、疏肝益阳小剂量治疗组[0.5 g/(kg.d)]、大剂量治疗组[1 g/(kg.d)],灌胃给药疗程30 d。疗程结束后取海绵体组织,荧光定量PCR法检测VEGF、IGF表达,Western印迹法检测Akt1蛋白表达和磷酸化。颈动脉取血,ELISA法检测血浆VEGF、IGF含量。结果:大剂量治疗组VEGF、IGF mRNA相对表达量分别为0.77±0.04和0.78±0.05,血浆VEGF、IGF含量分别为(95.83±37.34)pg/ml和(20.45±3.83)ng/ml,p-Akt1/Akt1表达量为1.43±0.50;模型组VEGF、IGF mRNA相对表达量分别0.41±0.06和0.42±0.06,血浆VEGF、IGF含量分别为(28.59±24.97)pg/ml和(15.82±4.37)ng/ml,p-Akt1/Akt1表达量为0.93±0.14。大剂量治疗组以上指标均较模型组明显升高(P<0.05)。小剂量治疗组除血浆IGF含量外,也较模型组明显升高(P<0.05)。结论:疏肝益阳胶囊可显著增加AED大鼠阴茎海绵体组织VEGF、IGF和Akt1表达,对血管内皮功能具有改善作用。这可能是其治疗动脉性ED的重要机制。

Objective： Cytokines such as VEGF and IGF play an important role in maintaining the function of blood vascular endothelium.And Akt1 is an important molecule in the intra-cellular signaling transduction.This study aims to investigate the molecular mechanism of Shugan Yiyang（SGYY） capsule in the treatment of arteriogenic erectile dysfunction（AED） by detecting the expressions and phosphorylation of VEGF,IGF and Akt1 in AED rats.Methods： We established AED models in 60 three-month-old adult male SD rats by bilateral ligation of the internal iliac artery,and assigned them to a sham operation group,a model control group,a sidenafil group,a low-dose SGYY group（0.5 g/） and a high-dose SGYY group（1 g/）.After 30 days of gavage,we assayed the plasma concentrations of VEGF and IGF in the carotid artery of the rats by ELISA,detected the expressions of VEGF and IGF mRNA by real-time PCR and determined the expression and phosphorylation of Akt1 protein in the corpus cavernosum penis by Western blot.Results： In the model control group,the expressions of VEGF and IGF mRNA were 0.41±0.06 and 0.42±0.06,the plasma concentrations of VEGF and IGF were（28.59±24.97） pg/ml and（15.82±4.37） ng/ml,and the expression of p-Akt1/Akt1 was 0.93±0.14.While in the high-dose SGYY group,the expressions of VEGF and IGF mRNA were 0.77±0.04 and 0.78±0.05,the plasma concentrations of VEGF and IGF were（95.83±37.34） pg/ml and（20.45±3.83） ng/ml,and the expression of p-Akt1/Akt1 was 1.43±0.50.All the parameters above were significantly higher in the high-dose SGYY than in the model control group（P0.05）,and so were they in the low-dose SGYY group except the plasma concentration of IGF（P0.05）.Conclusion： SGYY can significantly upregulate the expressions of VEGF,IGF and Akt1 in the corpus cavernosum penis of AED rats,and improve the function of blood vascular endothelium,which is probably an important mechanism of SGYY capsule acting on AED.