| ObjectiveIn our study,we have established a variety of pharmacodynamic research models through chemical or electric stimulation.The mian examination indicators include penile intracavernous pressure,carotid blood pressure,femoral blood pressure and penile erection length.We explored the effect of the new compound TPN171H on penile erectile function in experimental animal models and may provide a new drug treatment for ED.Methods(1)ICP monitoring method was used to test the effect on erectile function of TPN171H in a dog model of erection induced by SNP stimulation.(2)ICP monitoring method was used to test the effect on erectile function of TPN171H in a dog model of erection induced by electric stimulation.(3)ICP monitoring method was used to test the effect on erectile function of TPN171H in a rat model of erection induced by electric stimulation.(4)The length of uncovered penis mucosa was measured to test the effect on the erectile function of TPN171H in conscious-rabbit model induced by SNP stimulation.Results(1)Effect of TPN171H on penile intracavernous pressure changes in dog models induced by SNP stimulation:In general,after TPN171H was administered intravenously in Beagle dogs,the ICP value,ICP relative,ICP/BP value and ICP/BP relative value increased induced by SNP stimulation.The ICP value change rates of TPN171H low dose(0.50 mg/kg)group,medium dose(1.00 mg/kg)group and high dose(2.00 mg/kg)group were-3.38±4.56%,21.71±8.14%,43.52±10.03%respectively.The change rate of ICP value after TPN171H medium dose group and high dose group was significantly different from that of-the negative control group(P<0.01).The relative values of ICP in the low dose group,medium dose group and high dose group were 0.97±0.05,1.22±0.08,1.44±0.10 respectively.Compared with the negative control,the relative values of ICP in the TPN171H medium dose group and high dose group increased significantly after administration(P<0.01).The ICP/BP change rates of TPN171H low dose group,medium dose group and high dose group were 17.91±1.83%,47.32±12.16%,77.11±15.54%respectively.There was a significant difference compared with the negative control group(P<0.01).The ICP/BP relative values after administration of TPN171H low dose,medium dose and high dose groups were 1.22 ±0.04,1.48 ± 0.12,1.77± 0.15 respectively.The ICP relative values in the TPN171H administration group were significantly increased(P<0.01)compared with the negative control group.The above results suggest that the administration of TPN171H 1.00-2.00 mg/kg in dog models can significantly increase the ICP value,ICP relative value,ICP/BP value and ICP/BP relative value induced by SNP stimulation and enhance the penile erectile function of Beagle dogs(2)Effect of TPN171H on penile intracavernous pressure changes in dog models induced by electric stimulation:The ICP value of TPN171H low dose(3.75 mg/kg)group,medium dose(7.50 mg/kg)group,high dose(15.00 mg/kg)group were 21.95±2.01 mmHg,24.37±2.76 mmHg,24.52±2.73 mmHg,respectively.The value were increased by 10.29%,23.04%,24.19%compared with the ICP value before administraton of TPN171H.The ICP relative value were 1.11± 0.14,1.23 ± 0.12,1.24± 0.14 respectively which were increased by 13.69%,24.03%and 20.57%.Compared with the negative control group,the middle dose group and the high dose group showed a significant increase in the relative value of ICP(P<0.01-0.05).The ICP/BP value of TPN171H low dose group,medium dose group,high dose group were 0.16 ± 0.01,0.19± 0.02,0.20± 0.04 respectively.The value were increased by 2.59%,29.27%and 33.78%compared with the ICP/BP value before administraton of TPN171H.The relative values of ICP/BP were 1.07±0.14,1.30±0.14 and 1.34±0.20 respectively which were increased by 7.11%,25.28%,29.54%.Compared with the negative control,the TPN171H middle dose group and high dose group showed a significant increase in the relative value of ICP/BP(P<0.01-0.05).The above results suggest that the administration of TPN171H 7.50-15.00 mg/kg in Beagle dog models can significantly increase the ICP value,ICP relative value,ICP/BP value and ICP/BP relative value induced by electric stimulation and enhance the penile erectile function of Beagle dogs(3)Effect of TPN171H on penile intracavernous pressure changes in rat models induced by electric stimulation:The ICP value of TPN171H low dose(1.25 mg/kg)groups,medium dose(2.50 mg/kg)groups,high dose(5.00 mg/kg)groups were 31.65±10.39 mmHg,38.63±6.50 mmHg,48.81±8.41 mmHg respectively,which were increased by 18.81%,41.81%and 56.64%compared with the ICP value before administraton of TPN171H.The relative values of ICP were 1.16 ± 0.16,1.43± 0.19 and 1.65 ± 0.45 respectively,which were increased by 26.09%,55.43%and 79.35%respectively Compared with the negative control group,the middle dose group and the high dose group showed a significant increase in the relative value of ICP(P<0.05).The ICP/BP value of TPN171H low dose group,medium dose group,high dose group were 0.30±0.14,0.40 ± 0.08 and 0.60 ± 0.16 respectively,which were increased by 25.00%,60.00%and 106.90%.The relative values of ICP/BP were 1.25 ± 0.30,1.60 ± 0.23 and 2.10 ±0.59 respectively,which was increased by 15.74%,48.15%and 94.44%.The TPN171H median dose group and high dose group showed a significant increase in ICP/BP value and ICP/BP relative value at the diffetent time point after administration compared with the negative control group(P<0.05).The above results suggest that the administration of TPN171H 2.50-5.00 mg/kg in rat models can significantly increase the ICP value,ICP relative value,ICP/BP value and ICP/BP relative value induced by electric stimulation and enhance the penile erectile function of rats.(4)Effect on erectile function of TPN171H in conscious-rabbit model induced by SNP stimulation:The maximum length of uncovered penis mucosa in the TPN171H low-dose+SNP group was 6.99 ± 1.79 mm.The maximum length of uncovered penis mucosa in the TPN171H medium dose + SNP group was 7.03±1.74 mm.The maximum length of uncovered penis mucosa in the TPN171H high-dose+SNP group was 9.19 ± 0.96 mm.The length of uncovered penis mucosa in the TPN171H low dose group,medium dose group,high dose group had a significant difference at different time points within 30 min of SNP injection compared with the group(without SNP injiection)(P<0.05).The above results suggest that the administration of TPN 171H 3.00-30.00 mg/kg in conscious-rabbit models induced by SNP stimulation can significantly increase the maximum length of uncovered penis mucosa and enhance the penile erectile function of rabbits.ConclusionUnder the conditions of this experiment,after the administration of TPN171H by different routes,the ICP relative value,ICP/BP value and the ICP/BP relative value was significantly increased in dog and rat models induced by SNP or electric stimulation;while the length of uncovered penis mucosa was also significantly increased in the conscious-rabbit model induced by SNP stimulation.In summary,TPN171H showed a significant enhancement of erectile function in a variety of experimental animal models. |
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