The Protective Effects Of Chrysophanol On The Multiple Organ Injury Induced By Cerebral Ischemia-Reperfusion Injury In Mice

Cerebral ischemia reperfusion injury is a complex pathophysiological process, a large number of studies show that [1,2]massive release of inflammatory mediators which can be spread to the heart, lung, liver,kidney and other organs, the systemic inflammatory response activation of inflammatory cells after cerebral ischemia reperfusion and even lead to multiple organ dysfunction syndrome(MODS multiple organ dysfunction syndrome). The traditional Chinese medicine monomer chrysophanol is one of the effective component of rhubarb, genus hydroxyanthraquinone,previous experimental studies show that chrysophanol has effect of antioxidant, anti apoptosis, anti hypoxia, neuroprotective,but the chrysophanol on cerebral ischemia reperfusion regulation of oxidative stress and apoptosis in multiple organs has not yet in-depth study. These links as the target in this experiment, to investigate the protective effect of chrysophanol on multiple organ injury after cerebral ischemia reperfusion and its possible mechanism.This study used the modified Himori[4] method to establish the mice model of cerebral ischemia-reperfusion, the experimental mice were randomly divided into control group, sham operation group, model group,rhubarb group(10, 1, 0.1 mg·kg-1). The 3 silent information regulator(silent information adjustment factor 3, SIRT3) and aquaporin 4(aquaporin4, AQP4) were determined in brain tissue and the expression of Caspase3 in liver tissue by immunohistochemistry; Using enzyme mark instrument and spectrophotometer determine the myocardial superoxidedismutase(SOD) and content of malondialdehyde(MDA). The plasma alanine aminotransferase(ALT), aspartate aminotransferase(AST),creatinine(CR), blood urea nitrogen(BUN) content were measured.Experimental results show that: compared with the sham group, in brain tissue of model group AQP4 mRNA and AQP4 mRNA expression was enhanced, SIRT3 expression decreased, myocardial tissue SOD activity was significantly lower, MDA content increased significantly, serum ALT and AST levels increased, liver caspase-3 and caspase-3 mRNA expression increased significantly. Compared with the model group, the chrysophanol group can be down regulated the expression of AQP4 mRNA and AQP4 mRNA, increased levels of SIRT3 expression,significantly increased the activity of SOD, reduce MDA content, reduced serum ALT and AST levels and Caspase-3 and caspase-3 mRNA expression was significantly reduced.In summary, chrysophanol on cerebral ischemia reperfusion injury has a protective effect, the mechanism may be through upregulation of SIRT3 expression, activation of superoxide dismutase(SOD), regulation of oxidative stress response. And downregulation of AQP4 expression and reduce the occurrence of cerebral edema. Down regulated the expression of Caspase3 mRNA and expression of Caspase-3, inhibit apoptosis.Cerebral ischemia reperfusion secondary to cardiac, liver damage,chrysophanol can protect brain from ischemia reperfusion of the heart,liver and other organ injury. The mechanism may is to improve the body’s antioxidant capacity and the downregulation of Caspase-3 expression and inhibition of cell apoptosis.