| ObjectiveTo investigate the influences and pathophysiological mechanism of simvastartin on prostatic hyperplasia of spontaneously hypertensive rats (SHR).Methods36 male SHR were included in this research, and Rats were divided into high dose (20mg/Kg/day,n=12),low dose (10mg/Kg/day, n=12) and control groups (n=12). Weights and basal tail artery blood pressure of rats were measured, and then high dose of simvastatin solution, low dose of Simvastatin solution, and distilled water (control group) were given to SHR separately with gastric tub. After 6 weeks, we measured weights and tail artery blood pressures of rats again, then collected blood from hearts and dissociate prostates of rats under anesthetizing status. Prostate tissue were weighted and then embedded in paraffin and sliced for Electron microscopy observation of ultrastructures. Enzyme linked immunosorbent assay (ELASIA) was used to measure serum Interleukin-6(IL-6),insulin-like growth factor-1(IGF-1,Angiotensin II (AngⅡ) concentration, and immunohistochemical method was used to check the endothelial nitric oxide synthase (eNOS) expression in prostate tissue.ResultCompared with control group, the high-dose simvastatin group were with lower prostate weight (0.53±0.15 vs 0.73±0.08 mg, P=0.005). The serum IL-6 level in all simvastatin groups were lower than control group (low-dose group compared with control group:16.49±2.10 vs.20.91±5.53, P=0.005; high-dose group compared with control group:16.75±1.35 vs 20.91±5.53 pg/ml, P=0.008). The serum IGF-1 level in high-dose simvastatin group were also lower than control group (1.49±0.08 vs 1.60±0.10 ng/ml, P=0.016). But there was no significant difference of serum Ang II level before and after drug interference among all groups. Electron Microscopy observation showed that in low-dose simvastatin group, basal cells and columnar cells were with edema, interstitial fibroblast nuclei heterochromatin concentrated and marginated, nucleus gap widened, and mitochondrion as well as endoplasmic reticulum decreased. In high-dose simvastatin group, the ultrastructure disorders in prostate tissue were more significant than low-dose simvastatin group. Immunohistochemical method showed that there was higher eNOS expression in prostate tissue in simvastatin groups compared to control group, and eNOS expression was correlated with simvastatin doses. Immunohistochemical method showed that there was higher eNOS expression ratio in prostate tissue in simvastatin groups compared to control group, and eNOS expression was correlated with simvastatin doses. Intervention groups compared with control group,p=0.046, the difference was statistically significant.ConclusionSimvastatin could inhibit the progression of benign prostate hyperplasia by inhibiting inflammatory factors, growth factors and angiogenesis. ObjectiveTo investigate the influences and pathophysiological mechanism of losartan on prostatic hyperplasia of spontaneously hypertensive rats (SHR).Methods36 male SHR were included in this research, and rats were divided into high dose (30mg/Kg/day,n=12),low dose (15mg/Kg/day, n=12) and control groups (n=12). Weights and basal tail artery blood pressures of rats were measured, then high dose of losartan solution (30mg/Kg/day), low dose of Losartan solution (15mg/Kg/day), and distilled water(control group) were given to SHR separately with gastric tub. After 6 weeks, we measured weights and tail artery blood pressures of rats again, then collected blood from hearts and dissociate prostates of rats under anesthetizing status. Prostate tissue were weighted and then embedded in paraffin and sliced for Electron microscopy observation of ultrastructures.Enzyme linked immunosorbent assay (ELASIA) was used to measure serum Angiotensin II (Ang II),insulin-like growth factor-1 (IGF-1),Interleukin-6(IL-6)concentration,andimmunohistochemic al method was used to check the endothelial nitric oxide synthase (eNOS) expression in prostate tissue.ResultThe losartan groups were with lower tail artery systolic blood pressure (low-dose group compared with control group:184.54±16.90 vs. 203.75±10.28 mmHg, P=0.013; high-dose group compared with control group:166.88±14.74 vs.203.75±10.28 mmHg,P<0.001).lower tail artery diastolic blood pressure (low-dose group compared with control group:136.71±14.28 vs.151.58±9.96 mmHg, P-0.022; high-dose group compared with control group:122.71±11.56 vs.151.58±9.96 mmHg, P<0.001), and lower weight of prostate tissue (low-dose group compared with control group:0.64±0.10 vs.0.73±0.08 mg, P=0.011, high-dose group compared with control group:0.50±0.17 vs.0.73±0.08 mg, P＜0.001). Electron Microscopy observation showed that in low-dose losartan group, basal cells and columnar cells were with edema, interstitial fibroblast nuclei heterochromatin concentrated and marginated, nucleus gap widened, and mitochondrion as well as endoplasmic reticulum decreased. In high-dose losartan group, the ultrastructure disorders in prostate tissue were more significant than low-dose losartan group. In losartan groups, the serum AngⅡwere higher than control group (low-dose group compared with control group:61.32±2.49 vs. 54.85±7.20 pg/ml, P=0.021; high-dose group compared with control group:65.49+6.78 vs.54.85+7.20 pg/ml, P＜0.001). The serum IGF-1 level were lower in high-dose losartan group than that in control group (1.50±0.11 vs.1.60±0.10 ng/ml, P=0.03), but serum IL-6 levels had no significant difference among the 3 groups. Immunohistochemical method showed that there was higher eNOS expression in prostate tissue in losartan groups compared to control group, which was correlated with losartan doses. Immunohistochemical method showed that there was higher eNOS expression ratio in prostate tissue in losartan groups compared to control group, which was correlated with losartan doses. Intervention groups compared with control group,p=0.039, the difference was statistically significant.ConclusionLosartan could inhibit the progression of benign prostate hyperplasia by inhibiting RAS and IGF-1 as well as inhibiting angiogenesis.
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