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Effects of Resveratrol on NALP3Expression after Ischemia-reperfusion Injury and Its Possible Mechanism

Author: DongWuSong
Tutor: YangJun
School: Three Gorges University
Course: Clinical Immunology
Keywords: NALP3 Resveratrol Myocardial ischemia Reperfusion injury Inflammasome
CLC: R285.5
Type: Master's thesis
Year: 2012
Downloads: 142
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Abstract


Objective We constructed the rat model of myocardial I/R injury in vivo. The ratswere pretreated with different concentrations of resveratrol,and then subjected to30minischemia and2h reperfusion. To explore whether resveratrol ould play the role ofprotecting myocardial ischemia and reperfusion injury; the NALP3inflammasomepathway is involved in ischemia-reperfusion injury; resveratrol protected of myocardialischemia reperfusion injury by inhibiting the pathway of the NALP3inflammasome.Methods50male SD rats were randomly divided into5groups (n=10): shamoperation group (Sham the Dimethylsulfoxide-saline2ml/kg), ischemia-reperfusion group(IR group,dimethyl sulfoxide-saline2ml/kg), low doses of resveratrol preconditioning+ischemia and reperfusion group (L-Res group, dimethyl sulfoxide-Resveratrol2.5mg/kg),mide doses of whiteResveratrol pretreatment+ischemia-reperfusion group (M-Res. group,dimethyl sulfoxide the-Resveratrol5mg/kg), high doses of resveratrol preconditioning+ischemia-reperfusion group (H-Res.group, dimethyl sulfoxide the-Resveratrol10mg/kg),to establish the model of myocardial ischemia and reperfusion, The rats were given drugsor saline via the right jugular vein15min before ligation,and then subjected to30minischemia and2h reperfusionall. All animals were sacrificed at2h postoperative. Lightmicroscope and transmission electronic microscope were used to observe structuralchanges of myocardium; Evans blue and TTC staining method were used to estimatemyocardial infarct size; CK-MB and TnT concentration were detected by automaticbiochemical analyzer; myocardial NALP3, Caspase1,IL-18, IL-1β,NF-κB p65weredetected by Real-time PCR or Western blot; blood IL-18and IL-1β levels analyzed byenzyme-linked immunosorbent assay (ELISA).Results (1) Pathological morphological examination showed normal morphology ofthe myocardial ultrastructure and organization of the Sham group; IR group myocardialstructural were serious damaged, pathological changes were dose-dependent significantimproved in resveratrol pretreatment groups;(2)Infarct size which was found to be43.2±1.5%of the IR group,were reduced when pretreated with different concentrations ofresveratrol,the H-Res group myocardial infarct size was significantly reduced (25.5±1.2%,P <0.05); the M-Res myocardial infarct size (30.4±1.9%, P <0.05), still statisticallysignificant difference; the changes of the L-the Res (39.4±1.4%) not statisticallysignificant.(3) Ischemia-reperfusion group compared with Sham group, serum TnT (4.65± 0.43VS0.03±0.01, P <0.05) and CK-MB (1715±112.5versus780±115.4, P <0.05)were significantly increased;different concentrations of resveratrol pretreated,serum TnTand CK-MB levels became a dose-dependent reduction, M-Res group and compared withischemia-reperfusion group TnT (2.65±0.53vs4.65±0.43ug/l, P<0.05) and CK-MB(1284±121.8vs1715±112.5u/l, P <0.05) decreased significantly; the H-Res groupdecreased more significantly.(4) Compared with Sham group, NALP3, Caspase1, IL-1βand IL18mRNA expression in myocardial tissue were significantly (Sham of12.7times,15.9times,5.7times and9.9times increase) increased after ischemia and reperfusion, Theexpression was dose-dependent inhibitioned by resveratrol intervention.(5) The NALP3,Caspase1and NF-κB p65protein levels in IR group were significantly increased comparedwith the Sham group (P <0.05),difference was statistically significant; and in adose-dependent reduce in resveratrol intervention groups.Protein expression of their level,by correlation analysis, the NALP3and Caspase1, NF-κB p65protein changes showed asignificant positive correlation, respectively, R20.9424and0.9843, P <0.05.(6) IL1β andIL18levels in the peripheral blood was significantly secretion after ischemia andreperfusion group compared with the Sham group, resveratrol concentration graduallydecreased.when the concentration at10mg/kg, IL1β (289.61±45.32vs.580.54±54.28, P<0.05) and IL18(325.72±41.38vs.610.34±45.94) significantly decreased comparedwith IR group.Conclusion (1) Resveratrol in a dose-dependent inhibition of myocardial ischemia andreperfusion damage;(2) NALP3and caspase1-gene and protein expression in myocardialtissue significantly increased after ischemia and reperfusion,high expression of NALP3and caspase1may be involved in the pathophysiological process of the MI/RI;(3)NALP3inflammasome in the process of myocardial ischemia-reperfusion injury activationand secretion of IL-1β and IL-18inflammatory cytokine-mediated cascade ofinflammatory response;(4) NALP3inflammasome activating caspase1may directlyactivate NF-κB signaling pathway during the process of myocardial ischemia andreperfusion injury;(5) Resveratrol may play the role of protecting myocardial ischemiareperfusion injury by inhibiting the expression and activation of NALP3inflammasome.

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