The Experimental Study To Explore The Moecluar Mechanism Of Cryoablation-induced ED

ObjectiveCryoablation-induced erectile dysfunction (ED) is a common complication in patients with prostate cancer undergoing argon-helium cryotherapy. This study was designed to explore the molecular mechanisms of cryoablation-induced ED and recovery of erectile function affected by neurovascular bundle injury with different freezing temperatures.Materials and Methods80adult SD rats were randomly divided into control group and experimental group which was divided into three subgroups:Group A, Group B, Group C Neurovascular bundle of rats from Group A, Group B and Group C were frozen by argon-helium freezers with temperature0°C,-40°C,-80°C respectively. Five rats of each group were randomly selected in the day of cryotherapy, in the2nd week, in the4th week and in the9th week. Apomorphine (APO) experiment were done to test erectile function before death, then we took the cavernous tissue of the penis to do RT-PCR experiments and immunohistochemistry in order to detected the difference of nNOS and eNOS expression on both the level of gene and protein expression.Results1There was no difference in erections between in2nd week, in the4th week or in the9th week and before Cryo (P>0.05) for the control group and Group A. Com paring to before Cryo in erections, significant difference existed between in the2nd week, in the4th week or in the9th week (P<0.001) for Group B and Group C.2No difference was found in erections between the control group and Group A in the2nd week, in the4th week or in the9th week (P>0.05). Comparing to the control group, Group B and Group C also became fewer in the2nd week, in the4th week or in the9th week(P<0.001). And Group C was fewer than Group B in the4th week (0.2±0.45Vs.2.0±1.58, P=0.040)3The expression of nNOS-mRNA was in the same level (P>0.05)between in the2nd week, in the4th week or in the9th week and before Cryo for the control group and Group A. However, the expression for Group B and C was less in the2nd week, in the4th week and in the9th week than before Cryo(P<0.001).4There was no significant difference for Group A, comparing to the control group, before Cryo, in the2nd week, in the4th week or in the9th week. But Group B and C were less than the control group, and Group C was less than Group B, in the2nd week, in the4th week and in the9th week.5For the control group and Group A, the expression of eNOS-mRNA before Cryo was the same as (P>0.05) in the2nd week, in the4th week or in the9th week. Comparing to before Cryo, the expression in Group B was less in the4th week (1.10±0.078Vs.1.25±0.089, P=0.028) and in the9th week (0.77±0.050Vs.1.25±0.089, P<0.001). However, Group C was only less than before Cryo in the9th week (0.84±0.073Vs.1.19±0.035,P<0.001).6Comparing to the control group, the expression of eNOS-mRNA was the same level (P>0.05) in Group A at any time, was less (P<0.001) in Group B and C in the9th week.7Comparing to before Cryo in the expression of nNOS, there was no significant difference (P>0.05) in the control group and Group A, but obvious decrease (P<0.001) in Group B and C, in the2nd week, in the4th week and in the9th week. Group C has a lower level than Group B in the time above.8Comparing to the control group, no difference existed in Group A in the expression of nNOS at any time, and Group B and C decreased obviously in the2nd week, in the4th week and in the9th week.9The expression of eNOS in the control group and in the Group A. comparing to before Cryo, was no obvious difference (P>0.05) in the2nd week, in the4th week and in the9th week. The expression significantly decreased in Group B in the4th week (7.17±0.280Vs.7.93±0.122, P=0.002) and in the9th week (5.03±0.142Vs.7.93±0.122, P<0.001), and the tend was only found in the9th week in Group C (4.90±0.629Vs.7.82±0.317, P<0.001).10There was no obvious difference (P>0.05) between Group A and the control group in the expression of eNOS at any time. Significant difference appeared in Group B and C, comparing to the control group, in the9th week (P<0.001).Conclusion1. Cryoablation-induced ED caused directly by damage of neurovascular bundle, but erectile function recovery over time.2. The change of the expression of NOS including nNOS and eNOS, is the molecular mechanism of cryoablation-induced ED.3. Freezing temperature will affect the occurrence and recovery of cryoablation-induced ED, and higher temperature is more conducive to the recovery of erectile function.