科研之友
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摘要
The purpose of the present study was to investigate the effect of Luteolin(Lut) on myocardial ischemia reperfusion injury and explore the underlying mechanism. Myocardial ischemia reperfusion injury (I/R) model was induced with 30 min of left anterior descending (LAD) occlusion followed by 24 h of reperfusion. In vivo, the rats were randomly divided into 5 groups: (1) Sham, (2) I/R, (3) I/R + Lut(40 mg/kg), (4) I/R + Lut(80 mg/kg) and (5) I/R + Lut(160 mg/kg). In vitro, the H9c2 cells were assigned to five groups: (1) control, (2) hypoxia-reoxygenation(H/R), (3) H/R + Lut(5 mu M), (4) H/R + Lut(10 mu M) and (5) H/R + Lut (20 mM). The H9c2 cells were stimulated with H/R protocol in the presence or absence of TAK-242, a TLR4 inhibitor. As a result, Lut ameliorated myocardial ischemia reperfusion injury and hypoxia-reoxygenation as evidenced by triphenyl tetrazolium chloride (TTC) staining and MTT assay, respectively. Lut was founded to decrease the levels of aspartate transaminase(AST), creatine phosphokinase-isoenzyme (CKMB) and lactate dehydrogenase (LDH) in serum. Moreover, Lut could reduce the contents of interleukin1 beta(IL-1 beta), interleukin-18 (IL-18) and tumor necrosis factor-alpha (TNF-alpha) in serum of rats and supernant of H9c2 cells. In addition, Lut remarkably downregulated the expressions of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and nuclear factor kappa B (NF-kB). Lut also inhibited the upregulations of inflammasome components, such as NOD-like receptor 3(NLRP3), apoptosis-associated speck-like protein containing CARD(ASC) in I/R-induced rats and H/R-induced H9c2 cells. In conclusion, Lut exhibited strong favorable cardioprotective effect on myocardial I/R injury which might be related to the down-regulation of the TLR4-meidated NF-kB/NLRP3 inflammasome in vivo and in vitro.
