Influence and pathophysiological mechanisms of simvastatin on prostatic hyperplasia in spontaneously hypertensive rats

Urol Int. 2013;91(4):467-73. doi: 10.1159/000350519. Epub 2013 Jul 6.

Abstract

Objective: To explore the effects and mechanisms of simvastatin on prostate hyperplasia in spontaneously hypertensive rats (SHRs).

Methods: Thirty-six male SHRs were randomly divided into three groups: the 10 and the 20 mg/kg/d simvastatin group and the control group. After 6 weeks the ultra-microscopic prostate structures were observed. The serum levels of interleukin-6 (IL-6), insulin-like growth factor (IGF-1) and angiotensin II (Ang-II) were measured by enzyme-linked immunosorbent assays. The endothelium-derived nitric oxide synthase (eNOS) expression was evaluated with immunohistochemistry.

Results: Compared to the control group, the 20 mg/kg/d simvastatin group presented with lower absolute (p = 0.005) and relative prostate weight (p = 0.009). The basal cells and columnar cells presented with edema, condensed heterochromatin in interstitial fibroblast nuclei, widened nucleus gaps, and decreased mitochondria and endoplasmic reticulum in the 10 mg/kg/d simvastatin group, these changes were more pronounced in the 20 mg/kg/d simvastatin group. The IL-6 levels in the 10 and 20 mg/kg/d simvastatin groups were lower than those of the controls (p = 0.005 and p = 0.008). The IGF-1 levels of the 20 mg/kg/d simvastatin group were reduced compared to the control group (p = 0.016).

Conclusions: Simvastatin can delay and inhibit prostatic hyperplasia and progression in SHR. These actions may be mediated through the suppression of inflammatory and growth factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / blood
  • Animals
  • Endoplasmic Reticulum / drug effects
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression Regulation
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Immunohistochemistry
  • Inflammation
  • Insulin-Like Growth Factor I / metabolism
  • Interleukin-6 / blood
  • Male
  • Mitochondria / drug effects
  • Nitric Oxide Synthase Type III / metabolism
  • Prostatic Hyperplasia / drug therapy*
  • Prostatic Hyperplasia / physiopathology*
  • Rats
  • Rats, Inbred SHR
  • Simvastatin / therapeutic use*

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Interleukin-6
  • Angiotensin II
  • Insulin-Like Growth Factor I
  • Simvastatin
  • Nitric Oxide Synthase Type III
  • Nos3 protein, rat