Crosstalk Between Apoptosis And Autophagy In Rat Prostates After Androgen Ablation And Benigin Prostatic Hyperplasia In Castrated Rats

Objective:This study was researched on the relationship between apoptosis and autophagy in rat prostate tissues with time in rat models of castration and benign prostatic hyperplasia meantime,the cleavage fragments of Beclin-1 protein and the level of apoptosis over time was also observed,and whether androgen can effectively inhibit the level of apoptosis in rat prostate tissues.Methods:A total of 63 male Sprague-Dawley rats of 8 weeks and 250±110 g were under researched.In the model of castration,Sprague-Dawley rats were under the excision of bilateral testes and sacrificed the rats on the 1,2,4,8,16 and 28 days after surgery.The control group directly got prostate tissues.40 male Sprague-Dawley rats were randomly divided into two groups—Castraion+Solvent group and Castration+Testosterone group.For the Castration+Solvent group,rats were received surgery of the free rat testis but not excised and injection of 1 ml solvent(orange oil plus 10%ethanol solution)consecutively by subcutaneous in the hind legs after one week of surgery,At the same time,rats in the Castration+Testosterone group would received excised the testis of both sides and injection wih testosterone propionate 0.5 mg/d(dissolved in 1 ml of ethanol solvent)consecutively by subcutaneous in the hind legs after one week of surgery.Sacrificed the rats in the 1,4,8,16 and 28 days after injected with testosterone or solvent.Rat prostate tissues were weighed and divided into two parts,one with fixed with 10%formaldehyde solution in 24 hours and embedded in papraffin for HE staining,the another with stored in liquid nitrogen and stored in-80? refrigerator for detect the level of autophagy band apoptosis over time.Results:Compared with the Control group,the weight of prostate and prostate index were significantly decreased(P<0.05)in Castration group.The weight of prostate and prostate index increased significantly in Castration+Testosterone group on 4,8,16 and 28 days compared with Castration+Solvent group.Western blot results displayed that basal levels of LC3-? protein could be detected in Control group,from 1 to 8 days,the expression level of LC3-? was significantly increased(P<0.05)in Castration group;From the beginning of the 16 days,the expression level of LC3-? protein decreased significantly(P<0.05)in Castration group.Westem blot showed that the Caspase-3 decreased significantly from 16 days after castration.The cleavage of PRAP-1 increased significantly from 8 to 16 days and the expression of PRAP-1 decreased from 28 days after castration(P<0.05).Compared to Castration+Solvent group,the cleavage of Beclin-1 increased significantly and the protein of LC3-? increased significantly(P<0.01)in Castration+Testosterone group.Tunel results showed that the level of apoptotic of prostate tissues after castration increased significantly on 2,4,8,16 and 28 days compared to Control group(P<0.05).Tunel results displayed that the level of apoptotic decreased significantly in Castration+Testosterone group compared to the Castration+Solvent group from 4 to 28 days.Conclusion:After autologous castration,the activation of autophagy plays a compensation role for the prostatic hyperplasia in the early stage,the level of apoptosis was gradually increased following the autophagy,hereafter the level of autophagy was decreased but the level of apoptosis was not significantly changed.Caspase-3 was activated and expression showed decreased significantly which presented apoptosis entered an irreversible stage.The way of cell died in the pro static hyperplasia were different on the different stages,maybe most prostate epithelial cells died through autophagy or it controlled the majority in the early stage and largerly by the apoptosis in the latter stage after castration.The cleavage of Beclin-1 increased significantly after the decreased of autophagy,at the same time,the level of apoptosis decreased,which probably showed that androgen can inhibited Beclin-1-C and increased autophagy."Autophagy-apoptosis" were not independent of each other,but was interrelated in the deprivation of androgen and the induction of benign prostatic hyperplasia.