The Effects And Mechanisms Of Atorvastatin On Aging Kidney

Objective:Morphological changes of aging kidney are characterized by glomerulosclerosis and interstitial fibrosis.Aging is an independent risk of chronic kidney disease,and age-related renal impairment can damage the kidney function. However,there are no effective drugs on the kinds of kidney disease,because the mechanisms of age-related renal impairment are not clear up to now.Recently research show that the wildly prescribed drugs,Statins,a HMG-CoA reductase inhibitors,appear to play beneficial roles in renal disease by cholesterol-lowing and cholesterol-independent passway.The aim of our study hope to evaluate whether atorvastatin had positive effects on age-related renal impairment and explore the possible mechanisms.Methods:20-month-age normal female Wistar rats were divided into three groups(n=9 in each Group).Group A were fed atorvastatin 10 mg/kg/day every day; Group B were fed atorvastatin 1 mg/kg/day every day;Group C fed the same volume normal saline served as control.3-month-age normal female Wistar rats(n=9) also served as normal control.All the rats were sacrificed after four months.Kidney weight,serum creatinine(Scr) and blood-lidpoids were measured.Paraffin sections of renal tissues were stained with PAS,Sirius red and PCNA(Proliferating cell nuclear antigen).Sclerosis index of glomerulus was calculated.The mRNA and protein expressions of matrix metalloproteinase(MMP-9,MMP-2),tissue inhibitors of metalloproteinase(TIMP-1,TIMP-2),transforming growth factor-β1(TGF-β1) and peroxisome proliferators activated receptors(PPARs) were examined by RT-PCR and Western blot respectively. Results:Renal mass diminution was found in all the groups of aging rats.The level of blood-lidpoids of aging rats was higher than that of young rats.The level of serum cholesterol and low-density lipoprotein(LDL) were decreased in Group A (both p＜0.05) and only LDL decreased in Group B(p＜0.05).Morphological changes of aging kidney were focal segmental glomerulosclerosis,widen of mesangial region,infiltration of inflammatory cells and sclerosis of arteriole,The treatment of atorvastatin improved the pathologic changes in the aging rats significantly,expecially in the group A.The expression of MMP-9 and TGF-β₁ were upregulated(p＜0.05 & p＜0.01) in the aging rats.Atorvastatin can reverse these phenomenons in aging rats.It can not only downregulated the expression of MMP-9 and TGF-β₁ but also upregulated the expression of TIMP-1.Atorvastatin can upregulated the expression of PPARα,PPARβand PPARγ(p＜0.01,p＜0.01 & p＜0.05).Conclusion:Atorvastatin can notable improve the pathological changes of aging kidney.All these effects may induced by lowing of blood-lidpoids,unbalance of MMPs/TIMPs and downregulated the expression of TGF-β.Atorvastatin also can upregulated the expression of PPARs in aging rats,but whether the effects of atorvastatin depend on the high expression of PPARs is not clear.More studies are need in the further.