胱硫醚-γ-裂解酶和胱硫醚-β-合成酶在高血压大鼠阴茎海绵体中的表达

目的:探讨高血压对大鼠阴茎海绵体组织胱硫醚-γ-裂解酶(CSE)和胱硫醚-β-合成酶(CBS)表达的影响及与大鼠勃起功能的关系。方法:健康雄性SPF级自发性高血压大鼠(SHR)与对照组WKY(Wistar-Kyoto)大鼠各10只,于12周龄时测定大鼠血清睾酮、阴茎海绵体内压/平均动脉压(ICP/MAP)、血浆和阴茎海绵体内源性H2S的含量,采用免疫组化和Western印迹分析CSE和CBS在阴茎海绵体内的表达。结果:SHR与WKY大鼠的血清睾酮值没有显著差别,SHR的ICP/MAP在0、3和5 V电刺激盆腔神经节(MPG)时均显著低于WKY组(n=10,P0.05)。SHR血浆H2S含量显著低于WKY大鼠(10.49±1.35)μmol/Lvs(21.92±2.75)μmol/L,P0.05],SHR阴茎海绵体组织内源性H2S含量显著低于WKY大鼠(52.60±3.44)nmol/mg prot vs(87.67±2.12)nmol/mg prot,P0.05],SHR阴茎海绵体组织内源性H2S生成率也较WKY大鼠显著降低(1.14±0.07)nmol/(mg·min)vs(4.35±0.32)nmol/(mg·min),P0.05]。CSE及CBS主要表达在SHR和WKY大鼠阴茎海绵体平滑肌细胞和血管内皮细胞的胞质,SHR的CSE及CBS蛋白表达量均显著低于WKY大鼠(P0.05)。ICP/MAP与CSE和CBS表达呈高度正相关(r=0.955、0.977,P均0.05)。结论:高血压大鼠阴茎海绵体组织中CBS和CSE的表达下降,导致阴茎海绵体内H2S合成减少,可能是高血压引起勃起功能下降的机制之一。

Expressions of CSE and CBS in the corpus cavernosum of spontaneous hypertensive rats

Objective： To investigate the expressions of cystathionine gamma-lyase （CSE） and cystathionine beta-synthase （CBS） in the corpus cavernosum of spontaneous hypertensive rats （SHR） and their relationship with erectile dysfunction. Methods ： This study included 10 male SHRs and 10 healthy male Wistar-Kyoto （WKY） rats as controls, all aged 12 weeks. We applied a series of electric stimuli to the major pelvic ganglions of the rats, observed changes in the ratio of intracaveruosal to mean arterial blood pressure （ICP/MAP）, measured the levels of serum testosterone （T） and endogenous H2S, and determined the expressions of CSE and CBS in the corpus cavernosum by Western blot and immunohistochemistry. Results ： No obvious difference was found in the serum T level between the two groups. Compared with the WKY rats, the SHRs showed significant reduction in the ICP/MAP ratio, the contents of plasma H2 S （ 21.92 ± 2.75 ]μmol/L vs 10.49 ± 1.35 ] μmol/L, P 〈 0.05 ） and endogenous corpus cavernosal H2 S （ 87.67 ± 2.12 ] μmol/mg prot vs 52.60 ± 3.44 ] nmol/mg prot, P 〈 0.05 ）, the level of endogenous H2 S synthesis （ 4.35 ± 0.32 ] nmol/mg per min vs 1.14 ± 0.07 ] nmol/mg per min, P 〈 0.05 ） and the expressions of CBS and CSE （P 〈 0.05）. Immunohistochemistry showed that CSE and CBS were distributed mainly in the smooth muscle cells and vascular endothelial cells of the corpus cavernosum. The ICP/MAP ratio was highly positively correlated with the expressions of CSE （ r = 0. 977, P 〈 0.05 ） and CBS （ r = 0. 955, P 〈 0.05 ） in the corpus cavernosal tissue. Conclusion： Hypertension inhibits endogenous H2 S synthesis by suppressing the expressions of CSE and CBS in the corpus cavernosum, which might be related with hypertension-induced reduction of erectile function.