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目的观察去势大鼠阴茎海绵体胱硫醚γ裂解酶(cystathionine-γ-lyase,CSE)/硫化氢(Hydrogen sulphide,H2S)与血红素加氧酶2(heme oxygenase,HO-2)/一氧化碳(carbon monoxide,CO)的交叉调控作用,初步探讨勃起功能障碍的发病机制。方法雄性SD大鼠制备去势大鼠模型,分别施加锌原卟啉(ZnPP,HO阻断剂)和炔丙基甘氨酸(PAG,CSE阻断剂)干预,检测基础条件下和阿扑吗啡(Apomorphine,APO)刺激后的海绵体内压(Intracavernous pressure,ICP)和勃起率;通过Western-blot、敏感硫电极和分光光度计分别检测大鼠勃起不同时期Zn PP(HO阻断剂)对CSE/H2S系统的影响,PAG(CSE阻断剂)对HO-2/CO系统的影响。结果基础条件和APO刺激后去势组、去势PAG组和Zn PP组与假手术组比较,ICP和勃起率下降(P<0.01),且去势PAG组和Zn PP组较去势组ICP明显下降(P<0.01);阿朴吗啡刺激勃起前和勃起中,去势组和去势Zn PP(HO阻断剂)组较假手术组CSE蛋白表达和H2S含量下降(P<0.05),且勃起中去势Zn PP组较去势组CSE蛋白表达和H2S含量明显降低(P<0.05);勃起后去势组和去势ZnPP(HO阻断剂)组较假手术组H2S含量下降(P<0.01)。勃起前和勃起中去势组和去势PAG(CSE阻断剂)组较假手术组HO-2蛋白表达和CO含量下降(P<0.05),且勃起中去势PAG组较去势组HO-2蛋白表达和CO含量明显降低(P<0.05);勃起后去势组和去势PAG(CSE阻断剂)组较假手术组CO含量下降(P<0.01)。勃起前、勃起中和勃起后,CSE和HO-2蛋白表达分别呈正相关(r=0.732,0.850和0.727),H2S和CO水平分别呈正相关(r=0.765,0.912和0.929)。结论 CSE/H2S与HO-2/CO交叉调控作用与去势大鼠勃起功能障碍有关。
Objective To observe the effects of cystathionine-γ-lyase (CSE) / hydrogen sulfide (H2S) and heme oxygenase (HO-2) / carbon monoxide (carbon monoxide, CO) cross regulation, preliminary study of erectile dysfunction pathogenesis. Methods Ovariectomized rats were induced by zinc protoporphyrin (ZnPP, HO blocker) and propargyl glycine (PAG, CSE blocker) respectively. The basal conditions were compared with that of apomorphine (ICP) and erectile rate induced by Apomorphine and Apomorphine (APO) were detected by Western blotting. Sensitive sulfur electrodes and spectrophotometer were used to detect the effect of Zn PP (HO blockers) on CSE / H2S system impact, PAG (CSE blocker) on the HO-2 / CO system. Results Compared with the sham operation group, the ICP and erectile rate decreased significantly (P <0.01) in the OVX group and the castrated PAG group and the Zn PP group. (P <0.01). Before apomorphine stimulation, the expression of CSE protein and the content of H2S in sham operation group were significantly lower than those in sham operated group (P <0.05) Compared with sham operation group, the content of H2S and the content of H2S in ovariectomized Zn PP group were significantly lower than those in sham operation group (P <0.05) P <0.01). HO-2 protein expression and CO content in edentulous and erectile castration castration and castrated PAG (CSE blocker) group were significantly lower than those in sham operation group (P <0.05) (P <0.05). The content of CO in the evisceration castration group and the castrated PAG (CSE blocker) group was significantly lower than that in the sham operation group (P <0.01). There was a positive correlation between CSE and HO-2 protein expression (r = 0.732, 0.850 and 0.727, respectively) before erection, erection and erection. There was a positive correlation between H2S and CO levels (r = 0.765, 0.912 and 0.929 respectively). Conclusion Cross-regulation between CSE / H2S and HO-2 / CO is associated with erectile dysfunction in ovariectomized rats.