Expression Of HIF-1α In Benign Prostatic Hyperplasia Of Obese Mice And Intervention Of Aerobic Exercise

Objective:The study was based on a high-fat diet induced obese mice benign prostate hyperplasia,mainly conducted to observe expression of hypoxia-inducible Factor-1α(HIF-1α),vascular endothelial growth factor(VEGF)and other hypoxia-related proteins in tissues through a four-week treadmill exercise intervention and to explore the mechanism which induced obese mice prostatic hyperplasia by high-fat diet and the effect of aerobic exercise on BPH.Methods:39 SPF C57BL/6J mice were randomly divided into two groups:(1)control group(control,CON group,n=15)fed normal diet;(2)High fat diet group(HFD group,n=24)fed High fat diet.After 12 weeks of dietary intervention,6 mice were randomly selected from each group.The model was established successfully by increasing prostate index significantly in HFD group compared to the CON group.After successful modelling both CON(n=9)(named SD)and HFD(n=9)groups continued to be fed with their respective diets.HFD group was randomly divided into two groups of obesity group(OB,n=9)and training group(T,n=9).T group had a treadmill exercise covering 14m/mins,60mins/day,and 6 times a week for 4 weeks.After the intervention,blood samples were collected,and prostate tissue was stripped.Serum lipid was detected by ELISA.HIF-1α,VEGF and microvessel density(MVD)were measured by immunohistochemistry.Histopathological changes of prostate were observed by HE staining.The relative expression of HIF-1α,Bcl-2,Bax in prostate tissue was analyzed using Western Blot.Experimental results with M±SD,statistical method with group difference between testing by independent sample t-test and single factor analysis of variance,correlation analysis using Pearson correlation analysis,The significance difference is represented by p<0.05.Results:1.The average body weight of the HFD group was 1.2 times that of the CON group at 9~thh week,with a significant increase(p<0.01).After 12 weeks of high-fat diet,the body fat rate of the HFD group(6.63%±0.85%)was significantly increased compared to the CON group(3.00%±0.69%)(p<0.01).2.The prostate volume,prostate mass,prostate index and prostate cavity area of mice in the HFD group were significantly increased compared with those in the CON group(p<0.01).3.IOD(sum)values of HIF-1αin prostate tissues of HFD group significantly increased compared with those of CON group(p<0.01).4.According to Pearson product moment correlation analysis,PV was positively correlated with TG(r=0.573,p=0.007),and PV was positively correlated with LDL(r=0.830,p=0.000).5.After 4 weeks of aerobic exercise,there was no significant change in the average weight of mice in the OB group and the T group(p>0.05).The weight change rate of mice in the T group was significantly lower than that in the OB group(p<0.05).6.There was no significant difference in the changes of prostate mass,prostate volume and prostate index in obesity-induced prostate hyperplasia mice after 4 weeks of aerobic exercise(p>0.05).7.Compared with SD group,HIF-1α,VEGF were significantly increased(p<0.01),and mean MVD was significantly increased(p<0.05)in the prostate tissues of OB group.Compared with the OB group,HIF-1αin the prostate tissue of the T group was significantly decreased(p<0.05),VEGF,mean MVD were not significantly changed(p>0.05).8.Compared with the SD group,the relative expression of total Bcl-2,Bax in the prostate tissues of OB group was higher(p<0.01),and the relative expression of total Bax protein was higher(p>0.05),but there was no statistical significance.Compared with the OB group,the relative expression of total Bax in the prostate tissues of the T group was increased(p<0.05),and there was no significant difference in the relative expression of total Bcl-2 protein(p>0.05).Conclusions:1.12 weeks of high-fat diet intervention can induce obesity with BPH in mice;2.12 weeks of high-fat diet intervention resulted in hypoxia in the prostate tissue of mice accompanied by increased expression of HIF-1αin the prostate nucleus3.4 weeks of aerobic exercise can reduce the area of prostate gland cavity and inhibit the performance of BPH;4.The expression of HIF-1αin prostate cell nucleus can be decreased through 4weeks of aerobic exercise to inhibit the hypoxia of prostate tissue;5.Aerobic exercise stimulates the expression of apoptosis-inducing factor Bax in prostate tissue,which promotes the apoptosis of prostate cells and thus controls the deterioration of BPH.6.The effect of 4-week aerobic exercise on the inhibition of BPH in OB mice was not obvious,which may be related to the short intervention time of aerobic exercise.