Protective Effect Of Atorvastatin On Acute Renal Tubular Injury Induced By Contrast Agents In Rats With Renal Insufficiency

Objective:To study the acute injury of non-ionic low osmolar contrast media iohexol to renal tubular in rat with renal insufficiency and the protective effect of different doses of atorvastatin on the contrast agent-induced acute tubular injury.Methods:45male wistar rats were randomly divided into five groups:normal control group, model group, iohexol group, low-dose atorvastatin group and high-dose atorvastatin group. Applying the method of right nephrectomy, left renal artery narrowing (30%) to produce renal insufficiency model in rats. Two weeks after the operation, the statin groups were given atorvastatin10days ig, the other groups were given normal saline ig. In the tenth day, the normal control group and model group were given normal saline by tail vein injection, the iohexol group and the statin groups were given low osmolar contrast media (iohexol) by tail vein injection. Three rats of each group were sacrificed in24h,72h and7th day after injection of contrast agent. Take venous blood through the inner canthus vein and measure BNU, Scr values, measure the values of kidney injury molecule-1(KIM-1), N-acetyl-beta-D-amino-glucosidase (NAG) in urine by ELISA, cut off the left kidney and observe the tubular structural changes by HE staining, including tubular lumen, tubular type, tubular epithelial cell morphology and computing the scores of tubular injury, measure the renal tubular cell apoptosis rates by TUNEL and compare the differences of each group.Results:Before and in24h,72h and7th day after the injection of contrast agents(normal saline), BUN and Scr values in model group were significantly higher than the normal control group (P<0.01), But the values of KIM-1, NAG in urine, the rates of apoptosis of renal tubular cells, renal tubular injury risk scores were no significant difference (P>0.05). Compared with the model group, the values of BUN in72h, values of Scr,KIM-1and NAG, the rates of apoptosis of renal tubular cells, renal tubular injury risk scores of Iohexol group were higher, the differences were statistically significant(P<0.01). Compared with the Iohexol group, the values of KIM-1and NAG, the rates of apoptosis of renal tubular cells in low-dose atorvastatin group were lower, the differences were statistically significant(P<0.05). But the value of BUN Scr and renal tubular injury risk scores were no significant difference(P>0.05). Compared with the Iohexol group, the values of KIM-1and NAG, the rates of apoptosis of renal tubular cells, the renal tubular injury risk scores in high-dose atorvastatin group were lower, the difference was statistically significant (P<0.01), Compared with low-dose atorvastatin group, the values of KIM-1,NAG in urine, the rates of apoptosis of renal tubular cells, the renal tubular injury risk scores of high-dose atorvastatin group were lower, the differences were statistically significant (P<0.01),But the values of BUN, Scr and renal tubular injury risk scores were no significant difference(P>0.05).Conclusion:Renal hypoperfusion by renal artery narrowing have an injury on renal function. On the basis of renal insufficiency, the use of non-ionic low osmolar contrast media (iohexol) can further increase the acute injury to the kidney, especially the renal tubu-lar cells in rats.Continuous giving atorvastatin before using contrast agents can reduce the contrast agent-induced acute tubular injury and this protective effect was dose-effect relationship.