| Benign Prostatic Hyperplasia(BPH),also known as prostate gland enlargement,is a common condition in elderly males.It results in urinary problems such as urinary retention and urinary incontinence,and its rate of incidence increases with age.Past literature has shown that obesity,hypertension,hyperlipidemia,diabetes,insulin resistance and metabolic syndrome components are closely related to the occurrence and development of BPH.BPH is usually accompanied by low levels of chronic inflammatory reaction.The interplay between inflammatory reaction and metabolic syndrome accelerates the progress of BPH.Additionally,current research has confirmed that changes in absolute androgen and estrogen levels and their ratios play an important role in BPH development.Therefore,we postulate that effective control of the components of the metabolic syndrome and the level of regulatory hormones involved in BPH will boost the prevention and treatment of BPH.Aim1.Experimental studies-BPH rat models were treated with acupuncture,through acupoint Zhongji(CV3),followed by analysis of their prostate tissues for ERa,ER ? expression,to verify the effects of acupuncture treatment on BPH rat models.2.Clinical research-Obese BPH patients were treated with acupuncture and intervention with their Dai Meridian,then monitored for the efficacy of this treatment and deduction of its possible mechanism.Materials and Methodology1.Experimental studies:70 non-castrated SD rats were used.Through random selection,40 rats were treated with testosterone propionate to induce BPH(A),10 rats were treated with olive oil to induce BPH(B),and 20 rats were taken as blank group without any treatment(C).The experiment was divided into 2 sections:Section 1:After a span of 4 weeks,10 rats were each removed from Group A,Group B,Group C and analyzed.Section 2:After 4 weeks,10 rats in Group A were treated with acupuncture through acupoint Zhongji(CV3)for 8 weeks,while another 10 rats in Group A were treated with finasteride for 8 weeks.After the combined duration of 12 weeks,10 remaining control BPH rats in Group A,10 remaining blank rats in Group C,10 rats treated with Zhongji,and the 10 rats treated with finasteride were analyzed.Analysis of the rats involved removal of its prostate gland,to be observed for its prostate index,followed by HE staining,lHC,Western Blot,and PCR for ER a,ER P expression.2.Clinical research:32 BPH patients were divided into Dai Meridian group and Zhongji group and treated for 6 weeks.They were tested for IPSS,QOL score,sex hormone levels,prostate volume,residual urine volume,as well as the maximum urinary flow rate before and after treatment.Section 1:The patients were evaluated to determine the effects of intervention with the Dai Meridian and acupuncture treatment through Zhongji on BPH.Section 2:The patients were assessed to determine the association between Dai Meridian intervention and acupuncture treatment on the sex hormone levels,and in turn,the sex hormone levels on the symptoms of BPH patients.Section 3:The patients were evaluated to determine the effects of intervention with Dai Meridian on abdominal fat thickness,and therefore the relationship between abdominal fat thickness on the symptoms of BPH patients.Results(I)Experimental studiesSection 11.After 4 weeks,a statistically significant difference was found between the prostate index of treated group A against the control group B and blank group C(p<0.05).However,no significant difference was found in the prostate volume of the three groups(p>0.05).Nonetheless,a statistically significant difference was found in the prostate density of treated group A and control group B against blank group C(p<0.05).2.The control group B and treated group A were found to have a significant statistical difference in their testosterone levels(p<0.05)while blank group C and treated group A had a significant statistical difference in both their testosterone and estradiol levels(p<0.05).The remaining statistics were not found to have a significant difference(p>0.05).3.HE staining demonstrated that the glandular cells of treated group A became more irregular in shape,and the thickness of its glandular epithelium increased.In addition,the cells showed a thick intraglandular epithelia and its intercellular substances increased,coinciding with the trend of BPH patients.On the other hand,control group B showed enlargement of the cells of the prostate gland while the prostate cells of treated group A appeared smaller.4.IHC results showed that the expression of ER alpha protein was up-regulated in nucleus of epithelial cells,and down regulated in the cytoplasm of epithelial cells and stromal cells,and the expression of ER beta protein was up-regulated in the nucleus of epithelial cells,expressed in some of stromal cells,and up-regulated in the cytoplasm of the epithelial cells and the stromal cells.5.Western-Blot analysis revealed that there was no significant difference in the expression of ER? and ER? and their ratio after treatment(p>0.05).6.PCR results also indicated that there was no significant statistical difference in the expression of ER? mRNA,ER? mRNA after treatment(p>0.05).Section 21.After 12 weeks,no statistically significant difference was found in serum testosterone levels,estradiol levels and T/E2 ratio in the rats(p>0.05).2.Post intervention,there was no significant difference found in prostate index between blank group C,Zhongji group and finasteride group(p>0.05).When compared to the treated group A,however,there was a significant difference in prostate index(p<0.05).There was no significant difference found in prostate volume and density between treated group A and the rest of the groups(p>0.05).3.HE staining demonstrated that the prostate gland cells of Zhongji group appeared more regular in cell shape as compared to the prostate gland cells of treated group A.The extent of epithelial hyperplasia is also lower in the prostate gland cells of the Zhongji group,in comparison to that of treated group A and finasteride group.4.IHC results confirmed that acupuncture can down regulate the expression of ER alpha protein in cytoplasm,increase the expression of ER beta protein in nucleus,and down regulate the expression of ER beta protein in cytoplasm of stromal cells.5.Western-Blot analysis indicated that there was no significant difference between expression of ERa,ER? and ERa/ER? ratio of the cells of the prostate gland in all groups(p>0.05).6.According to the PCR results,a significant statistical difference was found between the expression of ER? mRNA in finasteride group and Zhongji group(p<0.05).On the other hand,there was no significant difference between the expression of ER? in the finasteride group and Zhongji group,when compared to treated group A and blank group C.The expression of ERa mRNA did not have a significant difference in all groups.(II)Clinical researchSection 11.After acupuncture intervention,a significant difference was found in the IPSS scores of both Dai Meridian group and Zhongji group after treatment(p<0.01),but there was no statistical difference between the two groups(p>0.05).2.Following acupuncture intervention,both Dai Meridian group and Zhongji group were found to have a significant statistical difference in their IPSS subdivision scores(p<0.05).Particularly,in terms of voiding interval and incidence of nocturia,there was a significant statistical difference between Dai Meridian group and Zhongji group(p<0.05).3.The QOL score of Dai Meridian group had a significant difference after treatment(p<0.05),while the QOL score of Zhongji group did not have a significant difference after treatment(p>0.05).However,there was no statistical difference between the two groups after treatment(p>0.05).4.Comparing the prostate volume of the Dai Meridian group and Zhongji group,there was no significant difference before and after treatment(p>0.05).Between the Dai Meridian group and Zhongji group,there was no significant difference in prostate volume as well(p>0.05).5.In terms of residual urine volume,there was a significant difference in Dai Meridian grorup before and after treatment(p<0.05),while there was no significant difference in Zhongji group before and after treatment(p>0.05).Comparing between both groups after treatment,there was no significant statistical difference(p>0.05).Section 21.The serum testosterone levels of patients in the Dai Meridian group and Zhongji group had a positive correlation with IPSS(p<0.05)and IPSS1(p<0.01).On the other hand,a negative correlation was found between estrogen and the age of BPH patients(p<0.05).The testosterone to estradiol ratio was found to have a positive correlation with IPSS5(p<0.05),and age appeared to have a positive correlation with IPSS7(p<0.05).IPSS5 had a negative correlation with prostate volume(p<0.01).2.Comparing serum testosterone levels,estradiol and T/E2 ratio,no significant difference was found in Dai Meridian group and Zhongji group before and after treatment,as well as in between the two groups(p>0.05).3.There was no correlation found between the sex hormone level and BPH index of the Dai Meridian group(p>0.05).In the Zhongji group,serum testosterone levels were found to have a positive correlation with the changes in IPSS 1 before and after treatment(p<0.05),while estradiol also had a positive correlation with residual urine volume(p<0.01).Lastly,T/E2 ratio was found to have a positive correlation with IPSS1(p<0.01)in the Zhongji group.Section 31.Analysis of correlation results of abdominal fat thickness shows that:SFT2 and IPS S3 are negatively correlated(p<0.05);SFT2 and residual urine volume are positively correlated(p<0.01);VFT1,VFT2 are positively correlated with BMI(p<0.05);VFT2 and QOL scores are positively correlated(p<0.05);AFH and IPSS1 are negatively correlated(p<0.01),PF and IPSS3 are negatively correlated(p<0.05),and UWI and IPSS6 are positively correlated(p<0.05).2.In the Dai Meridian group,a statistical difference was found in abdominal subcutaneous fat thickness and abdominal visceral fat thickness before and after treatment(p<0.05).Meanwhile,there was no significant difference in UVI,AHF,PF before and after treatment(p>0.05).3.A positive correlation was found between SFT1 and IPSS6,residual urine volume,maximum urine flow rate(p<0.05),while a positive correlation was found between PF and changes in IPSS7 before and after treatment(p<0.05).Conclusion1.Acupuncture through Zhongji acupoint had a positive therapeutic effect on BPH rats in treated group A,and the mechanism involved is speculated to be through the regulation of ERa and ER? expression in the hyperplasia sections of the prostate gland.2.Intervention with the Dai Meridian was beneficial to BPH patients,and it was superior to ordinary acupuncture,in terms of relieving the symptoms of lower urinary tract obstruction.This therapeutic effect of the Dai Meridian is correlated to the reduction of abdominal fat thickness,as seen in Section 3 of the clinical studies.3.Intervention with Dai Meridian has its therapeutic effects on BPH patients,through regulating the expression of ERa and ER?.At the same time,this intervention reduces the abdominal fat thickness of BPH patients,in turn relieving the clinical symptoms of BPH patients,therefore strengthening the therapeutic effects of this treatment. |
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