ABSTRACT
Objective To investigate the effect of diallyltrisulfide on rats with myocardial injury after coro-nary microembolization (CME). Methods 20 survival of SD rats were randomly divided into CME group (CME group)and diallyltrisulfide pretreatment group(DATSgroup),and these rats were injected with microspheres(42 μm in diameter)into the left ventricles to induce the model of CME, 10 rats for each group.DATS group was received diallyltrisulfide (DATS) 40 mg/(kg·d) for 7 days before operation. Another 10 survival of SD rats was selected as sham operation group(Sham group),and these rats were injected with the same dose of normal saline by left ventri-cles. Cardiac function was assessed by echocardiography and the expression of Akt and caspase-3 of myocardial tissue of rats in each group were detected by TUMEL staining,RT-PCR and Western Blot,while testing the level of cTnI after operation of 6 h. Results Compared with Sham group, the cardiac function of CME group and DATS group was significantly decreased (P<0.05), the expression of caspase3 mRNA and protein was significantly increased (P<0.05), the expression on Akt mRNA and protein was significantly decreased (P<0.05) (P<0.05). Com-pared with CME group, the cardiac function of DATS group was significantly improved (P<0.05), the expression of caspase3 mRNA and protein was significantly decreased (P<0.05), the expression of Akt mRNA and protein was significantly increased (P<0.05), cTnI level was significantly decreased (P<0.05). Conclusion Diallyltrisulfide pretreatment can significantly reduce the apoptosis of cardiomyocytes after CME and improve cardiac function.The mechanism may be through the inhibition of Akt to activate cardiomyocyte caspase3-mediated death receptor activa-tion pathway.
ABSTRACT
Objective To investigate the role of TLR4/NF-κB signaling pathway under the action of TAK-242 in the cardiomyocyte apoptosis after coronary micro-embolism (CME) in rats.Methods Fortyfive rats were randomized (random number) into three groups:sham operation,CME and CME plus TAK242 groups (n =15 per group).CME was induced by injecting polyethylene microspheres (42 μm) into the left ventricle except the sham group.CME plus TAK-242 group was treated with TAK-242 (2 mg/kg) via the tail vein of mice 30 min before CME modeling.Cardiac function was evaluated 6 h after operation.Tissue biopsy was stained with HBFP to measure the size of infarction area.TUNEL assay was used to detect cardiomyocyte apoptosis.Western blot and qPCR were used to evaluate the protein levels and mRNA expressions of TLR4,NF-κB p65 and cleaved caspase-3,respectively.Statistical analysis was performed using one-way analysis of variance followed by LSD-t test.Results Compared with the sham group,left ventricular ejection fraction (LVEF) in the CME group was significantly decreased [(68.91 ± 4.12) ％ vs.(84.80 ± 2.51) ％,P ＜ 0.05],and the infarction area (P ＜ 0.05),the apoptosis index [(3.36 ± 0.63) ％ vs.(0.19 ± 0.08) ％,P ＜0.05],the mRNA expressions of TLR4,NF-κB p65 and cleaved caspase-3 in CME group were increased significantly (all P ＜ 0.05).Compared with CME group,LVEF in the CME plus TAK-242 group was significantly improved [(75.58 ± 5.01) ％ vs.(68.91 ± 4.12) ％,P＜0.05],and the infarction area [(8.58 ± 2.12) ％ vs.(14.65 ± 4.23) ％,P＜0.05],the apoptosis index [(1.43 ± 0.51) ％ vs.(3.36 ± 0.63) ％,P ＜ 0.05],the mRNA expressions of TLR4,NF-κB p65 and cleaved caspase-3 in CME + TAK-242 group were decreased significantly (all P ＜ 0.05).Conclusions TAK-242 effectively improved CME-induced cardiac dysfunction by regulating TLR4/NF-κB signaling pathway and then reducing the cardiomyocyte apoptosis.