Preliminary Study Of ICA ? Combined With MET On Improving Erectile Function In T2DMED Mice

Objective: To investigate the effect of icariside ? combined with metformin on erectile function in mice with type 2 diabetes mellitus erectile dysfunction.Methods: A total of 20 male mice which were 5 weeks old with BKS-Leprem2Cd479/Nju(Lepr)KO/KO knockout were selected to make T2 DM model.All mice were fed in the same environment for one week.The T2 DMED mice were selected by the fasting blood glucose(FBG),mating test and apomorphine(APO)test.According to random number table method,T2 DMED mice were randomly divided into the ICA ?+MET group(n=10)and T2 DMED group(n=10).ICA ?+MET group mice were given icariside ?(ICA ?)and metformin(MET)daily.The daily dosage of ICA ? was 10 mg/kg.the daily dosage of MET was adjusted according to blood glucose level,and it was about 200 mg/kg.The mice in the T2 DMED group were given the same amount of normal saline.After 12 weeks of intragastric administration,there was a one-week washout period.The erectile function was evaluated by mating test and apomorphine(APO)test again.Serum and penile tissue were collected at the end of the experiment.The levels of fasting insulin(FINS),advanced glycation end products(AGEs)and their receptors(RAGE)in serum of experimental mice were detected with corresponding kits.The changes of smooth muscle fibers/collagen fibers(CCSMCs/CF)in the corpus cavernosum of experimental mice were measured by HE staining and Masson trichrome staining.Results: After the gavage intervention,(1)Compared with the mice in ICA ?+MET group,the mice in T2 DMED group were obese,depressed,slow-acting,less active,less lustrous fur,more food and water,and much urine with peculiar smell.Many mice had ulcers on their feet and tails.(2)The values of FPG and IR in ICA ?+MET group were significantly lower than those in T2 DMED group(P < 0.01),and the absolute values of ISI in ICA ?+MET group was lower than that in T2 DMED group(P < 0.05),but there was no significant difference in FINS between the two groups(P > 0.05).(3)In ICA ?+MET group,the number of mating mice,the number of erectile mice,erection frequency and erection rate were significantly higher than those of T2 DMED group(P < 0.01).(4)The levels of AGEs and RAGE in serum of ICA ?+MET group were lower than those in T2 DMED group(P < 0.05).(5)HE staining showed that the muscle fibers in the cavernous tissue of ICA ? + MET group were relatively uniform,and the nucleus was relatively clear;the muscle fibers in the cavernous tissue of T2 DMED group were disordered,and nucleus were pyknosis in part of cells.Masson staining showed that CCSMCs were red and CFs were blue.The distribution of CCSMCs in ICA ?+MET group was interwoven with collagen fibers and arranged regularly.However,the collagen content in the corpus cavernosum of mice in T2 DMED group increased significantly.The ratio of CCSMCs/CFs in the corpus cavernosum of mice in ICA ?+MET group was significantly higher than that in the corpus cavernosum of mice in T2 DMED group.Conclusion: The treatment of ICA ? combined with MET can reduce FPG,improve insulin resistance,reduce the content of AGEs and RAGE,improve CCSMCs/CFs ratio,and improve erectile function in T2 DMED mice.