The Experimental Study Of The Mechanism And The Protective Effects And Mechanism Of RhKD/APP On Renal Ischemia-reperfusion Injury In Rats

Renal ischemia-reperfusion injury is that the function of kidney tissue can not return to normal during the ischemia and after reperfusion, even the more serious tissue injury or organ function failure. The mechanism of acute ischemia-reperfusion injury is not clear, but the recent findings show that it relates to the production of radical, over-load of intracellular calcium, neutrophil, IL-8, apopotosis-gene regulatory, the detachment and attachment of renal tubular cells, the injury of renal tubular and glomerular cells mediated by NO, ET.This article reviews the protective effects and mechanism of human Kunitz protease inhibitor rhKD/APP on renal ischemia-reperfusion injury.From the aspect of the pharmacodynamics of organ-protection after renal ischemia-reperfusion injury, we make a multi-angle research of stability and high expression strain rhKD/APP screened by genetic combination technique. We established the ischemia-reperfusion model by knotting the kidney artery, and then observed the changes of renal function and kidney morphological structure after the treatment of ischemia-reperfusion injury by intervention of rhKD/APP. From the clinical and pathological aspects, we observed whether rhKD/APP has the protective effects on the renal ischemia-reperfusion injury and discussed the probable kidney protective mechanism of rhKD/APP based on three biggest network of renal ischemia-reperfusion mechanism the balance between the radical and anti-radical, the balance of inflammatory network, the balance between the cell apoptosis and anti-apoptosis.The results showed that rhKD/APP treatment group, compared with the sham group, had a less lift of SCr and BUN, and the tissue destruction was lighter than the latter in the aspect of morphological structure, it suggests that rhKD/APP has the protective effects on renal ischemia-reperfusion injury. During the research of the mechanism of kidney protection, we found that the content of MDA, NO and the activity of NAG in the rhKD/APP group decreased significantly, while the activity of SOD and GSH-PX increased significantly, it suggests that rhKD/APP played its role in radical scavenging in the renal ischemia-reperfusion; compared with the blank group, the content of serum MPO, TNF-a,NF-rB decreased significantly, it suggests that rhKD/APP can promote the inflammatory network balance; The TUNEL positive kidney cell of rhKD/APP group decreased significantly, and the extent of DNA breakage reduced significantly, it suggests that rhKD/APP exerts its function of kidney protection by anti-apoptosis effects. In conclusion, human Kunitz protease inhibitor rhKD/APP exerts the protective effects on renal ischemia-reperfusion injury by scavenging the radical, inhibiting the inflammatory mediators and anti-apoptosis effect.