Abstract:

BACKGROUND: Curcumin preconditioning can alleviate renal injury induced by limb ischemia/reperfusion, but whether curcumin preconditioning has protective effect on renal injury and its mechanisms are still poorly studied.
OBJECTIVE: To investigate the effects of the balance of matrix metalloproteinase-9/tissue inhibitor of metalloproteinase-1 when curcumin post-conditioning towards renal injury induced by limb ischemia/reperfusion in rats.
METHODS: Eighty adult male Sprague-Dawley rats were provided by Laboratory Center of China Medical University, and the study was approved by the Laboratory Animal Ethics Committee of Affiliated Central Hospital of Shenyang Medical College. The rats were randomly divided into four groups (n=20/group) using a random number table: sham, ischemia/reperfusion, curcumin post-conditioning and dexamethasone groups. Limb ischemia was induced by occlusion of bilateral femoral arteries of rats except for sham group for 4 hours, followed by reperfusion for 4 hours. At 4 hours after ischemia, 200 mg/kg curcumin and 1.5 mg/kg dexamethasone was immediately injected by intraperitoneal pathway into curcumin post-conditioning and dexamethasone groups, respectively. The same volume of normal saline was injected into the rats in the other two groups. Arteries blood samples were taken at 4 hours of reperfusion for examining biochemical indexes such as creatinine and blood urea nitrogen. Kidney was removed to detect the level of malondialdehyde. Hematoxylin-eosin staining was used to detect pathological changes and semi-quantitative score of renal tubulointerstitia. The expression levels of matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1 and nuclear factor-κB p65 mRNA were detected by western blot assay and RT-PCR, respectively. The levels of tumor necrosis factor-α and interleukin-1β in lung tissue were detected by ELISA.
RESULTS AND CONCLUSION: (1) Compared with sham group, the levels of creatinine, blood urea nitrogen and malondialdehyde in the ischemia/reperfusion group were significantly increased (P < 0.05). Hematoxylin-eosin staining showed obvious dilatation of renal tubules, tubular pattern, and disappearance of brush border and infiltration of inflammatory cells in renal interstitium in the lesion field. Semi-quantitative score of renal tubulointerstitia increased (P < 0.05). The expression levels of matrix metalloproteinase-9, nuclear factor-κB p65 mRNA and matrix metalloproteinase-9/ tissue inhibitor of metalloproteinase-1 were increased (P < 0.05). The release of tumor necrosis factor and interleukin-1 was increased (P < 0.05). (2) Compared with the ischemia/reperfusion group, the levels of creatinine, blood urea nitrogen and malondialdehyde in the curcumin post-conditioning group were significantly decreased (P < 0.05). Hematoxylin-eosin staining showed obvious dilatation of renal tubules, tubular pattern, and disappearance of brush border and infiltration of inflammatory cells in renal interstitium in the lesion field. Semi-quantitative score of renal tubulointerstitia decreased (P < 0.05). The expression levels of matrix metalloproteinase-9, nuclear factor-κB p65 mRNA and matrix metalloproteinase-9/ tissue inhibitor of metalloproteinase-1 were decreased (P < 0.05). The release of tumor necrosis factor and interleukin-1 was decreased (P < 0.05). (3) There was no significant difference in each index between curcumin post-conditioning and dexamethasone groups. (4) In summary, curcumin post-treatment can reduce the renal injury induced by limb ischemia/reperfusion injury in rats, which may be related to the reduction of matrix metalloproteinase-9/tissue inhibitor of metalloproteinase-1.

Key words:  curcumin, ischemia/reperfusion, curcumin post-conditioning, renal, matrix metalloproteinase 9, tissue inhibitor of metalloproteinase-1, limb ischemia/reperfusion, renal injury model