Защитный эффект l-аргинина на печеночную ишемию реперфузионного повреждения: экспериментальное исследование

Аннотация

A major problem complicating liver transplantation is the preservation injury that results from ischemia/reperfusion (I/R) injury after organ revascularization. The L-arginine-nitric oxide (NO) pathway has been recognized to play critical roles during organ injury and transplant rejection. Recent data indicates that NO synthesis has beneficial effects in several models of liver injury. The purpose of this study is to examine the role of L-arginine on preservation injury in an experimental model of rat I/R. Methods: Complete ischemia of the median and left hepatic lobes was produced by clamping the left branches of the portal vein and the hepatic artery for 45 min., than 2 h of reperfusion. Rats were pre-cotreated with L-arginine (25 mg/kg i.p.) for 3 days before, last time 10min before induced ischemia-reperfusion maneuver. Results: L-Arginine supplementation provided activation of a constitutive form of NO-synthase, thereby inducible NOS activity decreased, but remained its significantly higher than that of the control. L-Arginine influences also on the level of proinflammatory cytokines, and the content of IL-1β, IL-6 and TNF-α were decreased. Also L-Arginine decreased hepatic transaminase levels at the time of examination. Conclusions: The results show that L-arginine supplementation and NO synthesis improve hepatic injury and have a protective role in the I/R injury. The enhanced production of NO through the administration of L-arginine balanced NO-arginine system, proinflamantory cytokine profile, protect liver at I/R induced injury. The protective effect may be mediated by activation of cNOS-derived NO.