The Study Of Coccomyxa Gloeobotrydiformis Polysaccharide Alleviates Benign Prostate Hyperplasia Through Inducing Autophagy And Its Molecular Mechanism

Objective: Benign prostatic hyperplasia is one of the most common urological diseases in aging males,which is charactered by excessive proliferation of prostate epithelial and stromal cells.Among the pharmacological therapies for the treatment of benign prostatic hyperplasia,5α-reductase inhibitors are effective synthetic drugs,but longterm use of these drugs often leads to adverse side effects.This study aims to investigate the therapeutic effect of Coccomyxa gloeobotrydiformis polysaccharide on mice with benign prostatic hyperplasia and explore molecular mechanism from the point of autophagy regulation.Methods: 1.A mouse model of benign prostatic hyperplasia was induced by using testosterone propionate and then divided into control group,benign prostatic hyperplasia group and coccomyxa gloeobotrydiformis polysaccharide treatment group.Weigh mouse body weight and prostate weight to calculate prostate index,observe the prostate histological changes by H&E staining.2.Serum testosterone level was measured by ELISA,the expression of androgen receptor was detected by western blot.3.The expression of proliferation-related proteins(PCNA,Cyclin D1,P21)was detected by western blot,the expression of Ki67 was observed by immunohistochemistry and immunofluorescence and flow cytometry to detect the cell cycle.4.Transmission electron microscope was used to observe the formation of autophagosomes,the expression of autophagy and mitophagy-related proteins(LC3B,Beclin1,PINK1,Parkin,SQSTM1/P62)were detected by western blot,the expression of LC3 B was observed by immunofluorescence.5.The expression of AMPK(AMPK,p-AMPK)signal pathway was detected by western blot.Results: 1.Coccomyxa gloeobotrydiformis polysaccharide could reduce prostate weight and prostate index,serum testosterone and androgen receptor,and significantly alleviate the proliferation of prostate tissue in benign prostatic hyperplasia mouse model.2.Coccomyxa gloeobotrydiformis polysaccharide decreased the expression of proliferation related proteins(PCNA,Cyclin D1,Ki67)and increase the expression of P21,and arrested cell in the G1 phase.3.Coccomyxa gloeobotrydiformis polysaccharide upregulated the expression of autophagy and mitophagy-related proteins(LC3B,Beclin1,PINK1,Parkin),and downregulated the expression of autophagy receptor protein SQSTM1/P62.4.Coccomyxa gloeobotrydiformis polysaccharide may induce autophagy and mitophagy by activating AMPK signaling pathway.Conclusion: Coccomyxa gloeobotrydiformis polysaccharide can significantly induce autophagy and mitophagy by activating AMPK signaling pathway,thereby ameliorate benign prostatic hyperplasia.