Effects Of Atorvastatin-calcium On The Expressions Of SOCS-1 And NF-κBp65 After Renal Ischemia/Reperfusion Injury In Rats

Objective: To investigate the effect of atorvastatin-calcium on the expressions of SOCS-1 and nuclear factorκB(NF-κB) after renal ischemic-reperfusion injury in rat models.Methords: Fifty-four wistar rats were randomly divided into sham, ischemia-reperfusion(IR) and atorvastatin-calcium treated groups (each with n=18). Within each group, rats were further divided into three subgroups,IR6h,IR24h and IR48h groups (each with n=6). The rat models were established by bilateral clipping of renal arteries for forty-five minutes. The group of sham were same as the group of ischemia-reperfusion, but not clip. The treatment group received atorvastatin-calcium 10mg·kg-1·d-1 and the other groups only received the same volume physiological saline for one week before surgery. Histopathological damages were monitored accordingly. All the rats received daily gavage for one week. The levels of blood urea nitrogen and serum creatinine were measured after 6h,24h and 48h reperfusion, then the rats were euthanized in batch and histopathological damages were monitored accordingly. The expressions of SOCS-1,NF-κBp65 and ICAM-1 in renal tissue were measured by immunohisto-chemical stain.Results: 1. In the sham group, the organizational structure of kidney were normal. In the IR group, the renal tubular epithelial cells had different degree swelling, necrosis, fall off and inflammatory cells infiltrating obviously in renal interstitial. But in the atorvastatin-calcium treatment groups, the pathological changes improved obviously. 2. In the sham group, the levels of blood urea nitrogen and serum creatinine in the each point time were not changed clearly, but in the other groups, the levels of them were gradually increased after 6h reperfusion, to 24h of peak, 48h dropped, but still maintain high levels. In the atorvastatin-calcium treatment group, the levels of blood urea nitrogen and serum creatinine were markedly higher than those of the sham group at the same phase(each P <0.01), though lower than those of the IR group (each P <0.01) at the same reperfusion time points. 3. The levels of SOCS-1,NF-κBp65 and ICAM-1 were not expressed in the renal tissue, but expressed in the other groups. The levels of them were increased gradually after 6h reperfusion, to 24h of peak, 48h dropped, but still maintain high levels. After 24h reperfusion in the atorvastatin-calcium treatment group, the expressions of SOCS-1 were markedly higher than the same phase of IR group, while the content of NF-κBp65 and ICAM-1 were lower than those in IR group (each P <0.01). 4. In the IR group, the levels of NF-κBp65 and ICAM-1 were all positively related with the levels of serum creatinine and blood urea nitrogen, differences were statistically significant(r=0.965, r=0.894;r=0.954, r=0.888;each P <0.01). And the levels of SOCS-1 were also positively related with the levels of NF-κBp65 and ICAM-1, differences were statistically significant(r=0.807, r=0.772,each p<0.01).Conclusion: 1. Atorvastatin-calcium pretreatment protected kidney against ischemia after renal ischemia reperfusion injury through relieving the renal function and the organizational structure damage. 2. With the levels of blood urea nitrogen and serum creatinine whetherisolated changed, the levels of NF-кBp65 and ICAM-1 can reflect the severity renal dysfunction. 3. The levels of SOCS-1 were positively related with NF-κBp65and ICAM-1, it showed that SOCS-1 probably mediated the NF-κB signaling pathways. 4. Atorvastatin-calcium protected kidney against ischemia after renal ischemia reperfusion injury through regulated the expressions of SOCS-1 and inhibited the activity of NF-κBp65 in kidney.