Experimental Studies On Protective Effects Of Grape Seed Proantho-cyanidin Extracts On Renal Ischemia-reperfusion Injury In Rats

[Objective]To investigate the protective effects of GSPE on renal ischemia/reperfusion (I/R) injury in rats and the possible mechanisms.[Methods]Forty-five normal male Sprague-Dawley rats were randomly divided into 3 groups:sham-operated group(group A),I/R group(group B),GSPE-pretreated I/R group(group C).The rats in GSPE-pretreated I/R group were intraperitoneally administered with GSPE at the dose of 150mg/kg once daily for 5 days.The rats in other two groups were intraperitoneally administered with 0.9%NaCl saline solution at the dose of 10ml/kg once daily for 5 days.To induce ischemia-reperfusion injury,the rats were anesthetized with pentobarbital(50 mg/kg i.p.),and their left kidneys were exposed through small flank incisions.And the right kidneys were excised. The left renal pedicles of group B and group C were occluded with nontraumatic clamps for 60 min.At the end of the ischemic period,the clamps were released for blood reperfusion.Blood samples were taken at 1h,4 h and 24 h after reperfusion and tested for blood urea nitrogen(BUN),creatinine(Cr),superoxide dismutase(SOD), Malondialdehyde(MDA),tumor necrosis factor-a(TNF-a) and interleukin-10(IL-10). The expressions of ICAM-1 in renal tissue were detected by immunohistochemistry, and the pathological changes in renal tissue were observed by HE staining.[Results]The structure of renal tissue in sham-operated group was roughly normal. Renal tubular epithelial cells in I/R group manifested swelling,degeneration,necrosis, shedding and inflammatory cells infiltration.Compared with I/R group,the pathological changes in renal tissue were alleviated significantly in GSPE-pretreated I/R group. Compared with sham-operated rats,the levels of serum BUN in I/R group and GSPE-pretreated I/R group were closer after 1 hour renal reperfusion,and those in other subgroups were higher(P<0.05).I/R group and GSPE-pretreated I/R group showed significant increase in Cr,MDA,TNF-a,the expression of ICAM-1(P<0.05) and decrease in SOD and IL-10(P<0.05).Compared with I/R group,the levels of serum BUN and Cr in G SPE-pretreated I/R group were significantly decreased after 4,24h renal reperfusion(P<0.05).And the levels of serum BUN and Cr in GSPE-pretreated I/R group were not different statistically from those in I/R group af- ter 1 hour renal perfusion.Compared with GSPE-pretreated I/R group,I/R group showed significant increase in MDA,TNF-a,the expression of ICAM-1(P<0.05) and obvious decrease in SOD and IL-10(P<0.05).[Conclusion]GSPE had the protective effect on renal ischemia/reperfusion injury in rats.The protective mechanisms may be closely related to anti-oxygen free radicals, anti-lipid peroxidation and inhibition of inflammatory responses mediated by adhesion molecules.