The Study On The Effect Of Atorvastatin And N-acetyl Cysteine In The Rat Contrast Induced Nephropathy Model

Purpose:This study aims to establish the CIN rat model, give atorvastatin and NAC to CIN rats, then observing the changes of biochemical indicators and kidney structures, and discuss the effect of Atorvastatin and NAC on CIN rats and their mechanisms.Methods:1. Establised CIN rats model and divedied into3groups group:48h and72h after injecting of contrast medium injection, Scr of the rat model was rise25%tip than basic value. Forty five Wistar adult rats were randomly divedied into3groups: control group (group A), atorvastatin group (group B) and NAC group (group C). Three days Before and two days after injecting of contrast medium, group A, group B and group C were respectively given1.5ml saline,atorvastatin (30mg/kg), NAC (300mg/kg) to fill the stomach every day. all rats were killed72hours after injection of contrast material. serum creatinine (Scr), c-reactive protein (CRP), tumor necrosis factor alpha levels (TNF-a) were detected before and two days after injecting of contrast medium.Kidney specimens were saved.2. Processed specimens:Kidney tissues were cuted down for HE staining, immunohistochemiscal analysis, kidney skin and medulla were Separated, cortex were cuted into1mm3for Electronic microscopy observation, the levels of malondialdehyde (MDA), superoxide dismutase (SOD) and nitric oxide (NO) in kidney tissues were detected for ELISA method; the levels of protein expression of Bax and Bcl-2in kidney tissues were detected for Western Blot method,detecting the expression of VEGF mRNA as well.Result:1. Serum index:After48h, three groups of rats Scr, CRP, TNF-a levels were elevated (P＜0.05). As compared with the control group, Atorvastatin group and NAC group exhibited low serum levels of Scr, CRP and TNF-a (P＜0.05). As compared with NAC group, Atorvastatin group exhibited low serum levels of TNF-a (P＜0.05).2. The levels of MDA, SOD and NO:(1)The levels of MDA, atorvastatin group, NAC group were lower than the control group,and Atorvastatin group is lower than NAC group (P＜0.05);(2)SOD and NO levels, atorvastatin, NAC group were higher than the control group, and Atorvastatin group is higher than the NAC(P＜0.05).3. The protein expression of Bax and Bcl-2:(1)Control group Bax protein expression was higher than atorvastatin group and NAC group(P＜0.05), Control group Bcl-2protein expression was lower than atorvastatin group and NAC group(P<0.05),(2) Atorvastatin group compared to NAC group, these was no statistically significant differences between Bax and Bcl-2protein expression.4. The levels of VEGF mRNA:As compared with the controls,the levels of Atorvastatin group and the NAC group exhibited low level of VEGF mRNA (P＜0.05), Atorvastatin group compared to NAC group, these was no statistically significant differences between level of VEGF mRNA.5. Renal pathological morphological changes:(1)Changes under the optical microscope:In control group,renal tubule and renal interstitial showed a large number of inflammatory cells infiltration, renal tubular epithelial cells were severe swelled, Vacuolar degeneration;these were large number of tube types in The renal tubules, even occlusion. As compared with the control group, Atorvastatin group and NAC group pathological changes were lighter, especially Atorvastatin group;(2) Changes under the Electronic microscope:In control group,renal tubular basement membrane were thickened seriously,endothelial cell mitochondria were severe swelled, arrangement of crests were disordered, even disappeaedr, microvilli fell off on Lumen surface. As compared with the controls, Atorvastatin group and NAC group pathological changes were lighter, especially Atorvastatin.(3) immunohistochemical: TGFβ1was expressed in the three groups. The three groups high expression ratio were73.33%.26.67%.33.33%. Compared to control group, Atorvastatin group and NAC group expressed low levels of TGFβ1(P＜0.05), Atorvastatin group compared to NAC group, these was no statistically significant differences on the level of TGFβ1.Conclision:1. Anti-inflammatory, antioxidant stress may be the main mechanisms of atorvastatin and NAC main renal protection.2. Atorvastatin,NAC may reduce expression of Bax protein and increase expression of Bcl-2, Reduce the apoptosis of renal tubular epithelial cells,and play a preventive role in the prevention of CIN.3. Atorvastatin, NAC may reduce the levels of VEGF and TGFβ1, improve the kidney damages, can inhibit the happening of the CIN to a certain extent.