| Objective: High uric acid is reported to be an independent risk factor for erectile dysfunction(ED),which is germane with the occurrence of ED.However,after modification of renal function damage,high uric acid exhibits no significant effect on erectile function.Whether high uric acid has effects on erectile function remains unclear.The purpose of this study is to investigate the influence of high uric acid on ED and the potential mechanism,through analyzing the content of ROS,NO and the expression of eNOS,P-eNOS,n NOS,ROCK1,ROCK2 in the corpus cavernosum of hyperuricemic rats.Methods: 24 healthy male SD rats,8weeks old,were randomly divided into control group(Group A),hyperuricemia group(Group B),febuxostat group(Group C),hyperuricemia treated by febuxostat group(Group D).There were 6 rats in each group,which were gavaged with medicine after one week of adaptive feeding.The rats in group A were gavaged with normal saline(2ml/d);the rats in group B were gavaged with Potassium Oxonate(250 mg/kg?d)that was dissolved in 2ml normal saline;the rats in group C were gavaged with febuxostat(5mg/kg?d)that was dissolved in 2ml normal saline;the rats in group D were gavaged with both febuxostat(5mg/kg?d)and Potassium Oxonate(250mg/kg?d).4 weeks later,after animals being anesthetized,the changes of ICPmax/MAP in penile erectile function,the levels of serum testosterone in blood samples and renal function of all rats were tested.Then,corpus cavernosum was obtained from the sacrificed animals.ELISA was used to measure the content of ROS and NO.Immunohistochemistry and western blot were used to detect the expressions of eNOS,P-eNOS,nNOS,ROCK1,ROCK2.Results:the body weight(group A: 337±7.9g,group B:325.5±6.6g,groupC:329±7g,group D:330.8±7.5g),serum creatinine(group A:27.9±3.9?mol/l,group B:29.4±3.8?mol/l,group C: 30.2±3.4?mol/l,group D: 28.5±4.7?mol/l),blood urea nitrogen(group A: 7.2±0.8 mmol/l,group B: 7.5±0.7mmol/l,group C: 6.8±1.1 mmol/l,group D: 7.3±1.1 mmol/l),serum testosterone(group A: 461.7±74.4 ng/dl,group B: 456.9±71.7ng/dl,group C: 459.2±68.8 ng/dl,group D: 472±97.8 ng/dl),MAP(group A: 119.6±8.7mm Hg,group B: 126.4±4.7mmHg,group C:123.5±6.1mm Hg,group D:120.2±6.6 mm Hg)had no significant difference among the groups(P>0.05).The uric acid in group B(147.9±14.7?mol/l)was significantly higher than that in other groups(group A:45.9±4.9?mol/l,group C: 40.5±3.4?mol/l,group D: 47.5±5.3?mol/l)(P < 0.05).The content of ROS in group B(8833.9073±743.1458U/ml)was significantly higher than that in other groups(group A:5183.9379±527.5111 U/ml,groupC: 5462.8402±753.2719 U/ml,groupD: 5311.4930±560.1909 U/ml)(P <0.05).The content of NO in group B(31.5±2.71?mol/L)was significantly lower than that in other groups(group A: 40.18±3.25?mol/L,group C: 41.73±2.45?mol/L,group D:42.3±3.67?mol/L)(P <0.05).By measuring ICPmax/MAP in each group at 0V,3V,5V voltage stimulation,group B(0.1±0.01,0.41±0.06,0.49±0.04)was significantly lower than that in other groups(group A: 0.17±0.01,0.82±0.03,0.86±0.03;group C:0.18±0.01,0.78±0.02,0.86±0.02;group D:0.16±0.01,0.79±0.03,0.85±0.04)(P <0.05).Immunohistochemistry showed that eNOS and P-eNOS were predominantly showed in the vascular endotheliocytes and penile cavernous sinus.nNOS was mainly expressed in neurons.ROCK1 and ROCK2 were mainly expressed in the cytoplasm of corpus cavernosum smooth muscle cells.The result of immunohistochemistry was analyzed by integrated optical density(IOD).The expression of eNOS(IOD)in group B(502.33±92.09)was significantly lower than that in other groups(group A: 1022±250.35,group C: 969.33±162.13,gro-up D:979.67±187.79)(P <0.05).The expression of P-e NOS(IOD)in group B(413.17±54.06)were significantly lower than that in other groups(group A: 789.83±133.46,group C:806.83±103.25,group D:843.17±112.02)(P <0.05).The expression of n NOS(IOD)in group B(583.3±53.9)were significantly lower than that in other groups(group A:896.3±82.1,group C:903.8±108.5,group D:980±155.6)(P <0.05).The expressions of ROCK1 and ROCK2(IOD)had no significant difference among the groups(P>0.05).Western blot results were analyzed by using the Relative Optical Density(ROD).The expression of eNOS(ROD)in group B(0.33±0.06)were significantly lower than that in other groups(group A: 0.58±0.09,group C: 0.51±0.07,group D:0.55±0.09)(P<0.05).The expression of P-eNOS(ROD)in group B(0.22±0.06)were significantly lower than that in other groups(group A:0.45±0.08,group C:0.4±0.07,group D:0.42±0.07)(P <0.05).The expression of nNOS(ROD)in group B(0.3±0.02)were significantly lower than that in other groups(group A:0.59±0.02,group C: 0.6±0.02,group D:0.61±0.02)(P<0.05).The expressions of ROCK1 and ROCK2(ROD)had no significant difference among the groups(P>0.05).conclusion: high uric acid causing ED is possibly associated with the significant increasing of ROS,the significant reducing of NO and the significant decline of eNOS,P-eNOS,nNOS which may prohibit the NO/cGMP signaling pathway in corpora cavernosum. |
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