Protective effects of simvastatin on injured dopaminergic neurons in Parkinson's disease rats induced by lipopolysaccharide

Abstract

Objective To examine the effect of simvastatin treatment on Parkinson's disease rats induced by lipopolysaccharide(LPS) and its mechanism. Methods The LPS-PD model was established by injection of LPS (5 mg/mL) into the right substantia nigra compacta (SNC), and rats were randomly divided into control group, LPS-model group and simvastatin treatment group with 15 rats in each group. Rats in the simvastatin treatment group was intraperitoneally administered simvastatin (5 mg/kg) before, and daily for 14 days after surgery, while the control group and LPS-model group received same volume normal saline and LPS respectively. Ionized calcium binding adaptor molecule 1 (Iba-1)-positive cells and the expression of tyrosine hydroxylase (TH), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the SNC were detected by immunohistochemistry, Western blotting and enzyme-linked immunosorbent assay, respectively. The effect of simvastatin in the PD model was also examined in behavioral tests. Results The LPS-model group exhibited typical animal PD behaviors. Compared with the control group, the LPS-model group exhibited a decreased number of DA neurons, and comparison of the intact side to reduce 81.13% (P<0.01) in the SNC, as well as increases in the Iba-1-positive cell number, iNOS, IL-1β and TNF-α expression (P<0.05). These effects were inhibited by simvastatin treatment (P<0.05). Conclusion Simvastatin mediates a protective effect on dopaminergic neurons in the SNC in the LPS-PD model, possibly by inhibiting glial cells (astrocytes and microglia) activation, and playing an anti-inflammatory role, thus improving substantia nigra function. Key words: Parkinson's disease; Simvastatin; Lipopolysaccharide; Glial cells