Atorvastatin improves pathological changes in the aged kidney by upregulating peroxisome proliferator-activated receptor expression and reducing matrix metalloproteinase-9 and transforming growth factor-β1 levels

Objective: To investigate the effects of atorvastatin (AVT) on renal function and renal pathological changes in the aged rat and explore their possible mechanisms. Methods: Twenty-month-old, normal female Wistar rats were divided into three groups: group A (n=8) was fed high-dose AVT (10mg/kg/d); group B (n-8) was fed low-dose AVT (1 mg/kg/d); and group C (controls, n=8) received the same volume of normal saline; 3-month-old, normal female Wistar rats served as young normal controls (n - 8). All rats were sacrificed following a 4-month treatment period. Serum creatinine and blood lipid levels were measured. The glomerular sclerosis index and tubulointerstitial lesions were determined using renal periodic acid-Schiff-stained paraffin sections. The mRNA and protein expressions of matrix metalloproteinases (MMP)-9 and - 2, tissue inhibitors of metalloproteinase (TIMP)- 1 and - 2, transforming growth factor-beta 1 (TGF-beta 1), and peroxisome proliferator-activated receptors (PPARs) were examined using reverse transcription polymerase chain reactions and Western blots, respectively. Results: Serum lipid (including serum cholesterol and serum triglycerides) levels in aged rats were significantly higher than those in young rats (p < 0.05). Compared to the aged control group, high-dose AVT was associated with significantly lower serum total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels in aged rats (p < 0.05); low-dose AVT was associated only with lower serum LDL-C levels (p < 0.05). Renal morphological changes in aged rats included focal glomerulosclerosis, infiltration of inflammatory cells, and arteriole sclerosis. Improved renal pathology was observed in aged, AVT-treated rats, and included a decreased glomerular sclerosis index and tubulointerstitial lesion score, especially in those receiving high-dose AVT. Additionally, renal artery wall thickening, luminal narrowing, and arteriolosclerosis were significantly less severe in aged rats receiving high-dose AVT. Upregulated expression of MMP-9 and TGF-beta 1 was observed in the renal tissue of aged rats. AVT treatment was associated with a reversal of these phenomena and upregulated expression of TIMP-1, PPAR alpha, PPAR beta, and PPAR. in aged rats. Conclusion: AVT improved the renal pathology of aged rats. These effects may have been induced by the lowering of blood lipids, maintaining the MMP/TIMP balance, and downregulating the expression of TGF-beta 1. AVT may reduce the levels of MMP-9 and TGF-beta in aged rats by upregulating the expression of PPARs. (c) 2015 Elsevier Inc. All rights reserved.