| Objective: This study was based on the Insulin resistance induced by high-fat diet in mice,and through the intervention of 8-week treadmill exercise,it mainly observed insulinlike growth factor 1(IGF-1)and its receptor(IGF-1R)changes in serum and prostates of insulin-resistant mice and related downstream pathways for Extracellular signalregulated kinase(ERK)and AKT protein expression.To investigate the mechanism of benign prostatic hyperplasia in insulin-resistant mice and the effect of aerobic exercise on its improvement.Methods: 30 C57BL/6J mice of SPF grade 4-8 weeks old were randomly divided into two groups: the Control group(Control,group C,n=10)was fed normal diet,and the mice of the High fat diet(HFD group,n=20)were fed high-fat diet.After 12 weeks of dietary intervention,insulin tolerance test and glucose tolerance test were carried out,and the significant difference in the area under the blood glucose level curve between the two groups of mice was judged to be successful in establishing the insulin resistance model.Exercise intervention was conducted after successful establishment.Mice in group C continued to be fed normal diet,and those in HFD group continued to be fed high-fat diet.They were randomly divided into high-fat group(H group,n=10)and exercise group(E group,n=10).The exercise program of group E was Treadmill exercise for mice,14m/min,60min/ time/day,5 days per week,a total of 8 weeks.Insulin tolerance test and glucose tolerance test were performed after 8 weeks of aerobic exercise intervention.Collect blood,euthanize the mice,strip the prostate tissue weight(PW),calculate the prostate index(PI),and measure the prostate volume(PV)of mice in each group with water replacement method;Observe the histopathological changes of the prostate by HE stain;Histopathological changes of prostate were observed by HE staining;Detection of insulin and insulin-like growth factor 1(IGF-1)in serum by ELISA;Immunohistochemical detection of insulin-like growth factor 1 receptor(IGF-1R)in prostate;Western Blot was used to detect the relative expression levels of IGF-IR,AKT and ERK proteins in prostate tissue.The experimental results were expressed as M ± SD.Statistical methods used the independent sample t test to test for differences between the two groups;one-way analysis of variance was used to analyze the differences between multiple groups;p <0.05 was used for significance.Results: 1.After 12 weeks of diet induction,the area under the curve of insulin tolerance test and glucose tolerance test in the HFD group was significantly increased compared with that in the C group,and there was a significant difference between the two groups(p<0.01),indicating that the mice in the HFD group had insulin resistance;After 8 weeks of aerobic exercise intervention,compared with the H group,the area under the curve of insulin tolerance test and glucose tolerance test was significantly reduced in the E group,with significant difference between the two groups(p<0.05);Compared with group C,the serum levels of IGF-1 and insulin in mice in group H were significantly increased,and the results in the two groups were significantly different(p <0.05).Compared with group H,the serum levels of IGF-1 and insulin in mice in group E were significantlyreduced,and the results were significantly different(p<0.05);2.After 8 weeks of aerobic exercise intervention,PV(0.13±0.044)ml and PW(0.11±0.03)g in the H group were significantly increased compared with PV(0.08±0.03)ml and PW(0.07±0.02)g in the C group(p<0.05).There was no significant difference in PI between group H mice(2.34 ± 0.68)and group C mice(2.59 ± 0.78).There was no significant difference in the changes of PW,PV,PI and other related indexes in mice with insulin resistance and prostatic hyperplasia after 8 weeks of aerobic exercise;3.After 8 weeks of aerobic exercise intervention,HE staining was performed on the prostate tissues of each group and it was found that the prostate gland lumen of group C was normal and the prostate cells were in normal and regular distribution.Compared with group C,mice in group H had enlarged prostate gland lumen and irregular epithelial structure.Compared with group H,mice in group E had smaller prostate gland lumen and less irregular epithelial structure;4.After 8 weeks of aerobic exercise intervention,the positive expression of IGF-1R in prostate tissues of mice in group H was significantly increased compared with group C,while the positive expression of IGF-1R in prostate tissues of mice in group E was significantly decreased compared with group H;5.After 20 weeks,compared with group C,total proteins of IGF-1R,AKT and ERK in prostate tissues of group H were significantly increased(p<0.05).Compared with group H,total IGF-1R protein in prostate tissue of mice in group E was reduced,but there was no significant difference between the two groups.Total proteins of AKT and ERK in prostate tissues of mice in group E were significantly increased,and there was a significant difference between the two groups(p<0.05).Conclusion: 1.The 12-week high-fat diet induced insulin resistance in mice,and it was found in this experimental study that insulin resistance mice developed BPH,and the BPH model of IR mice was successfully established.2.The 8-week aerobic exercise intervention can reduce the concentrations of insulin and IGF-1 in the serum and significantly improve the insulin sensitivity of insulinresistant mice;It is possible to improve the BPH by down-regulating the expression of IGF-1R and its related proteins in the prostate tissue,reducing the area of the prostate gland cavity and inhibiting BPH;8 weeks of aerobic exercise had no significant effect on PV,PW and PI. |
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