Study On The Regulation And Its Mechanim Of17-Methoxyl-7-hydroxy-benzene-furanchalcone On NF-κB Signaling Pathway In Myocardial Ischemia Reperfusion Injury Rats

Objective: To investigate the protective effect of17methoxyl7hydroxy benzene furanchalcone (MHBFC) on NF-κB and inflammatory response in rats withmyocardial ischemia reperfusion injury (MI/RI).Methods: Rats with normal ECG were randomly divided into seven groups with10rats (half male and half female) per group: sham operation (Sham) group,myocardial ischemia reperfusion (MI/RI) group, MHBFC low dose (MHBFCL) group,MHBFC medium dose (MHBFCM) group, MHBFC high dose (MHBFCH) group,vehicle (DMSO) group and PDTC group.The animals were intravenouslyadministered via the tail vein with saline or corresponding drugs at a dosage of2ml/kg body weight once daily for7days. MHBFC and PDTC were diluted with0.5%DMSO and saline, respectively. The MI/RI operation was performed10min after thelast treatment. The rat MI/RI model was established by ligation of the left anteriordescending (LAD) for30min followed by ligation release for1h. The following indexes were determined at the end of reperfusion for60min:1. Areas of myocardial infarction was measured by Evans blue-TTC staining, thelevels of serum MDA, T-SOD, CK-MB, Hyp, AST and GSH-Px were assessed usingcommercial kits.2. Content of serum interleukin-1β (IL-1β), interleukin-6(IL-6) andinterleukin-10(IL-10) were measured by ELISA, MMP-9, ICAM, NF-κB, caspase-3and ANT1mRNA expression were evaluated using reverse transcription polymerasechain reaction (RT-PCR).3. TNF-α, NF-κBp65and intercellular adhesion molecule-1(ICAM-1) proteinexpression were evaluated by immunohistochemistry. NIK/IKK/IκB/NF-κB signalingpathway protein expression was evaluated by western blot (WB).Results:1. The infarction area (%) was expanded in the model group after MI/RI,and pretreatment with MHBFCMand MHBFCHsignificantly reduced the infarctionarea (%)(P<0.05). No significant differences were observed in the risk area (%)between the MHBFC groups and the model group. Pretreatment with MHBFCincreased activities of T-SOD and GSH-Px and decreased the levels of MDA, CK-MB,Hyp and AST.2. IL-1β and IL-6levels were lower in the MHBFC groups than in the modelgroup (P<0.05), the IL-10level was significantly elevated in MHBFC group comparedwith the model group (P<0.01). Compared with the model group, MHBFCpretreatment increased the ANT1mRNA expression (P<0.05) and decreased ICAM,NF-κB, MMP-9and caspase-3mRNA expression (P<0.01or P<0.05).3. MHBFC pretreatment down-regulated the expression of TNF-α，NF-κBp65and ICAM-1(P<0.01or P<0.05). Protein expression of NIK, IKKβ and NF-κBsignificantly increased and expression of IκB decreased in the model group,pretreatment with MHBFC decreased the expression of NIK, IKKβ and NF-κB and increased expression of IκB.Conclusion: The experiment showed that MHBFC protected the heart againstMI/RI in a dose-dependent manner via reducing lipid peroxidation damage, decreasingthe related apoptosis gene expression, while inhibiting NF-κB signaling pathway andthe inflammatory response.