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目的探讨氟哌啶醇对雄性大鼠阴茎勃起功能和一氧化氮合酶(NOS)基因表达及其活性的影响。方法将40只3月龄雄性Sprague-Dawley大鼠随机均分为氟哌啶醇组(20只)和蒸馏水对照组(20只,以下简称对照组)。对两组鼠均每日连续灌胃给药,氟哌啶醇组鼠为氟哌啶醇2mg/kg体质量,对照组鼠为与氟哌啶醇组同等容积的蒸馏水。分别在给药第3,6周时每组各随机取10只大鼠与发情期雌鼠进行交配实验,并判断阴茎勃起功能。以逆转录-聚合酶链反应法测定雄鼠阴茎海绵体组织神经型(nNOS)、内皮型(eNOS)、诱导型(iNOS)NOS的mRNA表达情况,并以NOS活性试剂盒测定总NOS活性(tNOS)以及结构型NOS(cNOS,包括nNOS、eNOS)和iNOS的活性。结果氟哌啶醇组鼠给药第3,6周时雄鼠骑跨次数(U均=6.5,P均<0.001)、阴茎插入次数(第3周U=8.0,P=0.001;第6周U=10.0,P=0.02)低于对照组鼠,差异有统计学意义;两者比率(插入命中率)在给药第6周时亦低于对照组鼠,差异有统计学意义(U=19,P=0.019)。给药第3周时氟哌啶醇组鼠阴茎海绵体组织eNOS mRNA表达低于对照组鼠,差异有统计学意义(t=-3.379,P=0.003);给药第6周时eNOS及nNOS mRNA表达均低于对照组鼠,差异有统计学意义(eNOSt=-3.846,P=0.001;nNOSt=-5.773,P<0.001);iNOS mRNA表达在给药第3,6周均未见有明显影响。氟哌啶醇组鼠给药第3,6周阴茎海绵体组织tNOS、cNOS活性低于对照组鼠,差异有统计学意义(t=-2.173～-4.184;P=0.001～0.048),iNOS活性的差异无统计学意义。结论结构型NOS基因表达以及NOS活性降低,可能是氟哌啶醇长期应用后阴茎勃起障碍的发生机制之一。
Objective To investigate the effects of haloperidol on penile erectile function and nitric oxide synthase (NOS) gene expression and activity in male rats. Methods Forty three-month-old male Sprague-Dawley rats were randomly divided into haloperidol group (20) and distilled water control group (20, hereinafter referred to as control group). The rats in both groups were given continuous gavage daily with haloperidol 2 mg / kg body weight for haloperidol and distilled water equal to haloperidol for control. At the 3rd and 6th week of administration, 10 rats in each group were randomly selected to mating experiment with estrous females, and the erectile function was evaluated. The mRNA expression of neuronal (nNOS), endothelial (eNOS) and inducible (iNOS) NOS was measured by reverse transcription polymerase chain reaction (RT-PCR) tNOS) and structural NOS (cNOS, including nNOS, eNOS) and iNOS. Results The number of male rodent rodents at the 3rd and 6th week of haloperidol treatment was significantly higher than that of the control group (U = 6.5, P <0.001, P <0.001) (P = 0.02, P = 0.02) was lower than that of the control group, the difference was statistically significant; the ratio of the two groups (insertional hit rate) P = 0.019). At 3 weeks after administration, the expression of eNOS mRNA in corpus cavernosum of haloperidol group was lower than that in control group (t = -3.379, P = 0.003); eNOS and nNOS (eNOSt = -3.846, P = 0.001; nNOSt = -5.773, P <0.001). No significant expression of iNOS mRNA was detected in the 3rd and 6th week after administration influences. The activity of tNOS and cNOS in corpus cavernosum of rats in the haloperidol group was lower than that in the control group at 3 and 6 weeks (t = -2.173 ~ -4.184; P = 0.001 ~ 0.048), iNOS activity The difference was not statistically significant. Conclusion Structural NOS gene expression and decreased NOS activity may be one of the mechanisms of penile erection disorder after long-term use of haloperidol.