目的观察高脂血症导致勃起功能障碍大鼠阴茎海绵体平滑肌RhoA/Rho激酶(ROCK)变化,探讨RhoA/ROCK导致高脂血症大鼠勃起功能障碍的机制。方法将40只SD雄性大鼠按随机数字表法分为实验组20只(高脂饲料喂养24周)和对照组20只(正常饲料喂养24周)。喂养前、后检测实验组和对照组大鼠血脂水平,检测喂养后实验组和对照组大鼠阴茎海绵体内压变化(ΔICP)/平均动脉压(MAP)比值,应用Western印迹检测两组大鼠阴茎海绵体平滑肌总RhoA、ROCK1、ROCK2及平滑肌细胞膜RhoA、细胞质RhoA蛋白表达。结果喂养24周后,实验组大鼠血胆固醇、三酰甘油和低密度脂蛋白明显高于喂养前及对照组(均P〈0.01)。喂养后实验组大鼠ΔICP/MAP比值明显低于对照组(P〈0.01)。喂养后实验组大鼠阴茎海绵体平滑肌ROCK2蛋白表达明显高于对照组(0.77±0.10比0.27±0.08,P〈0.01),两组总RhoA、ROCK1蛋白表达差异无统计学意义(均P〉0.05)。实验组大鼠阴茎海绵体平滑肌细胞胞质RhoA蛋白表达低于对照组(1.66±0.09比1.79±0.15,P〈0.05);胞膜RhoA蛋白/胞质RhoA蛋白比值明显高于对照组(0.33±0.09比0.26±0.07,P〈0.05)。结论RhoA/ROCK表达上调可能参与高脂血症大鼠勃起功能障碍的发生。
Objective To investigate the expression of RhoA/Rho-kinase (ROCK) in penile corpus cavernosum smooth muscles in rats of hypedipidemia-induced erectile dysfunction and its molecular mechanism. Methods Forty male Sprague-Dawley rats were randomly divided into control and experimental groups using a random number table. Rats in the control group ( n = 20 ) were fed with regular diet for 24 weeks and those in the experimental group (n = 20 ) with high-fat diet for the same period of time. The serum lipids profile was detected before and after the diet treatment. The ratio of intraeaveruosal pressure (AICP)/mean arterial pressure (MAP) was measured, and Western blot was used to detect the expression of total RhoA, ROCK1, and ROCK2 in penile corpus cavernosum smooth muscles, and RhoA protein in cell membrane and cytoplasm of smooth muscles after 24 weeks. Results After 24 weeks, the levels of cholesterol, triglyceride, and low-density lipoprotein were significantly higher in the experimental group compared with those before diet treatment and the control group ( all P 〈 0.01 ). AICP/MAP in the experimental group was greatly lower than in the control group ( P 〈 0. 01 ). The protein expression of ROCK2 in penile corpus cavernosum smooth muscles was higher in the experimental group than in the control group (0.77 ±0.10 vs 0.27 ±0.08 ,P 〈0.01 ) after 24 weeks, while no statistically significant differences were observed in total RhoA and ROCK 1 protein expression between the two groups ( both P 〉 0.05). RhoA expression in cytoplasm was lower in the experimental than in the control group ( 1.66 ± 0.09 vs 1.79± 0. 15 ,P 〈 0.05 ). The ratio of RhoA expression in menmbrane/cytoplasm was higher in the experimental than in the control group (0.33 ± 0.09 vs 0.26 ± 0.07, P 〈 0.05 ). Conclusion Up-regulation of RhoA/ ROCK may be involved in hyperlipidemia-induced erectile dysfunction in rats.