| Benign prostate hyperplasia(BPH), the most common disease in urinary system,has become one of the ten disorders of age which with high growth rate. Meanwhile, the "metabolic syndrome" is also a major chronic diseases serious harm to human health. In spite of many clinical researches about the relationship between the BPH and diabetes both at home and abroad in recent years, the pathogenesis between thistwo diseases need to be further explored. The objective of our study is to discuss the the diabetic effects on the morphological and biological changes of benign prostatic hyperplasia and discuss their possible mechanisms. This study includes two parts:Part 1 the establishment of diabetic rats with benign prostatic hyperplasia model and detections of the binding capacity of dihydrotestosterone(DHT) in and 5 alpha reductase activity in prostatic tissue.1 The establishment of diabetic rat models with benign prostatic hyperplasia and the detections of blood glucose level, insulin resistance index,the wet weight of prostate/avoirdupois and histopathologic diagnosisObjective:Observing the relationship between the diabetes mellitus and the BPH through the model establishment of diabetic rats with benign prostatic hyperplasia and the detections of blood glucose level,insulin resistance index(HOMA-IR),the wet weight of prostate/avoirdupois and histopathologic diagnosisMethods:The conventional breeding 6-8 weeks sexual mature Wistar rats,randomly divided into the normal group,BPH group, Type I diabetic rats induced by streptozotocin with benign prostatic hyperplasia(STZ+BPH group);purchasing the type II diabetic rats(GK rats) and diving into two group of GK rats with BPH group(GK+BPH group) and the group of GK rats with BPH under the treatment of pioglitazone hydrochloride(GK+BPH+PH group).Detecting the rats’ fasting blood glucose,avoirdupois, wet weight of prostate,fasting insulin(by ELISA) and observing the HE staining paraffin section of prostate tissues.Results:(1)Compared with normal group, the wet weight of prostate/avoirdupois has been a markedly increased in BPH group,STZ+BPH group,GK+BPH group and GK+BPH+PH group(P<0.05);(2)compared with BPH group, the wet weight of prostate/avoirdupois has been a markedly increased in STZ+BPH group,GK+BPH group and GK+BPH+PH group(P<0.05);(3) compared with BPH group, the wet weight of prostate/avoirdupois has no significant statistically difference in STZ+BPH group(P>0.05);(4)compared with GK+BPH group, the wet weight of prostate/avoirdupois has been a markedly decrease in GK+BPH+PH group(P<0.05);(5)compared with normal group,the HOMA-IR of GK+BPH group and GK+BPH+PH group has been a markedly increased(P<0.05),but there are no significant statistically difference in STZ+BPH group and BPH group(P>0.05);(6)compared with GK+BPH group,the HOMA-IR of GK+BPH+PH group hasbeen a markedly decrease(P<0.05);(7)Serum fasting insulin level was positively associated with prostate wet weight / body weight ratio.Conclusion:It was suggested that in,the wet weight of prostate/avoirdupois obviously higher than the normal group and the BPH group.In addition, when using the euglycemic agent(pioglitazone hydrochloride),the wet weight of prostate/avoirdupois obviously decreased compared with the unused group; in the rats with Type 1 diabetes mellitus(insulin absolutely lacking) and the BPH, the increasing of wet weight of prostate/avoirdupois has no statistically difference compared with the BPH group.So,we concluded that Type 2 diabetes mellitus’ insulin – resistant may promote the occurrence and development of BPH.2 The detections of binding capacity of dihydrotestosterone(DHT), 5alpha reductase activity in prostatic tissue of the rats with Type 2insulin- resistant diabetes mellitus and the BPHObjective:Detecting the rats prostate’s binding capacity of dihydrotestoserone(DHT) and 5 alpha reductase activity;exploring the relationship between diabetes mellitus and the rats prostate’s binding capacity of dihydrotestoserone(DHT),5 alpha reductase activity.Methods:The conventional breeding 6-8 weeks sexual mature Wistar rats,randomly divided into the normal group,BPH group, Type I diabetic rats induced by streptozotocin with benign prostatic hyperplasia(STZ+BPH group);purchasing the type II diabetic rats(GK rats) and diving into two group of GK rats with BPH group(GK+BPH group) and thegroup of GK rats with BPH under the treatment of pioglitazone hydrochloride(GK+BPH+PH group).Using the ether to remove endogenous hormones and detecting the combined DHT by ELISA after DHT combining the tissues.The content of DHT in tissues reflecting the binding capacity of DHT. Using the ether to remove endogenous hormones, adding testosterones and NADPH as hydrogen donor into the prostate tissue protein extracts, after a period of reaction, using the ELISA exam the levels of DHT.The levels of DHT reflect the activity of 5alpha reductase.Results:(1)Compared with normal group, the binding capacity of DHT has been a markedly increased in BPH group,STZ+BPH group,GK+BPH group and GK+BPH+PH group(P<0.05);(2)compared with BPH group, the binding capacity of DHT has been a markedly increased in GK+BPH group and GK+BPH+PH group(P<0.05),but there is no significant difference in STZ+BPH group(P>0.05);(3) compared with GK+BPH group,the binding capacity of DHT has a significant decrease in STZ+BPH group and GK+BPH+PH group(P<0.05);(4)compared with GK+BPH+PH group, the binding capacity in STZ+BPH group of DHT has a markedly decrease(P<0.05);(5)compared with normal group, the activity of type Iand II 5 alpha has been a markedly increasing in BPH group,STZ+BPH group,GK+BPH group and GK+BPH+PH group(P<0.05);(6)compared with BPH group,the activity of 5alpha reductase type Ihave no significant difference in groups of STZ+BPH,GK+BPH and GK+BPH+PH(P>0.05),but the activity of 5alpha reductase type IIhave shown significant increasing in those group;(7)compared with GK+BPH group,the group of GK+BPH+PH’s activity of 5alpha reductase type Ihas no significant difference(P>0.05),but the activity of 5alpha reductase type IIhas shown significant decreasing(P<0.05),the group of STZ+BPH’s activity of 5alpha reductase type Iand type IIhave no significant difference(P>0.05);(8)compared with GK+BPH+PH group,the group of STZ+BPH’s activity of 5alpha reductase type Ihave no significant difference(P>0.05) but the activity of 5alpha reductase type IIhas shown significant decreasing(P<0.05);(9)Serum fasting insulin level and DHT binding capacity, type II 5alpha reductase activity was positively correlated.Conclusion:This study shows that the binding capacity of dihydrotestosterone(DHT) and 5alpha reductase type IIactivity in prostate tissue of the rats with diabetes mellitus and the BPH apparently higher than normal rats and the rats of simple benign prostatic hyperplasia and the activity of 5alpha reductase type Ihave no significant difference compared with the rats of simple benign prostatic hyperplasia,higher than the normal rats.So,we may conclude that the diabetes mellitus could promote the occurrence and development of BPH by promoting the the activity of 5alpha reductase type Iand the binding capacity of dihydrotestosterone(DHT).Part 2 The function of TGF-β/Smad signaling pathway with IL-17 mediating in prostates of the diabetic rats with benign prostatic hyperplasia interstitial fibrosis.Objective:To exam the expression of IL-17 and α-SAM in prostate of type Iand type IIdiabetic rats and explain the signaling pathway of IL-17 to the rats’ BPH tissues.Methods:The conventional breeding 6-8 weeks sexual mature Wistar rats,randomly divided into the normal group,BPH group, Type I diabetic rats induced by streptozotocin with benign prostatic hyperplasia(STZ+BPH group);purchasing the type II diabetic rats(GK rats) and diving into two group of GK rats with BPH group(GK+BPH group) and the group of GK rats with BPH under the treatment of pioglitazone hydrochloride(GK+BPH+PH group).Extracting the m RNA from the prostate of rats,using the method of real-time PCR to detect detect m RNA expression levels ofIL-17 and α-SAM;detecting the protein expression levels of α-SAM by western blotting.Results:(1) normal group, the result of real-time PCR in prostate shows that the expression of IL-17 markedly increased in BPH group,STZ+BPH group,GK+BPH group and GK+BPH+PH group(P<0.05);(2) compared with BPH group, the result of real-time PCR in prostate shows that the expression of IL-17 markedly increased in STZ+BPH group,GK+BPH group and GK+BPH+PH group(P<0.05);(3) compared with GK+BPH group, the result of real-time PCR in prostate shows that the expression of IL-17 decreased in STZ+BPH group and GK+BPH+PH group(P<0.05);(4) compared with GK+BPH+PH group, the result of real-time PCR in prostate shows that the expression of IL-17 decreased in STZ+BPH group(P<0.05);(5) compared with normal group, the result of real-time PCR in prostate shows that the expression of α-SMA markedly increased in BPH group,STZ+BPH group,GK+BPH group and GK+BPH+PH group(P<0.05);(6) compared with BPH group, the result of real-time PCR in prostate shows that the expression of α-SMA markedly increased in STZ+BPH group,GK+BPH group and GK+BPH+PH group(P<0.05);(7) compared with GK+BPH group, the result of real-time PCR in prostate shows that the expression of α-SMA decreased in STZ+BPH group and GK+BPH+PH group(P<0.05);(8) compared with GK+BPH+PH group, the result of real-time PCR in prostate shows that the expression of α-SMA decreased in STZ+BPH group(P<0.05);(9) compared with normal group, the result of western blotting in prostate shows that the expression of α-SMA markedly increased in BPH group,STZ+BPH group,GK+BPH group and GK+BPH+PH group(P<0.05);(10)compared with BPH group, the result of western blotting in prostate shows that the expression of α-SMA markedly increased in STZ+BPH group,GK+BPH group and GK+BPH+PH group(P<0.05);(11) compared with GK+BPH group, the result of western blotting in prostate shows that the expression of α-SMA decreased in STZ+BPH group and GK+BPH+PH group(P<0.05);(12) compared with GK+BPH+PH group, the result of western blotting in prostate shows that the expression of α-SMA decreased in STZ+BPHgroup(P<0.05);(13)The level of fasting insulin in rat serum was positively correlated with the expression of IL-17 and α-SMA m RNA,α-SMA protein.Conclusion:The study show that the expression levels of IL-17 and α-SMA much higher in the prostates of rats with BPH compared with the normal rats. But,when the diabetic rats with benign prostatic hyperplasia, the expression levels of IL-17 and α-SMA higher than the simple BPH group. So, we may conclude that the IL-17 could promote interstitial fibrosis of prostate by activing the signal pathway of TGF- β/Smad to promote α-SMA protein expression in diabetic rats. |
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