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Objective To explore the potential mechanism of Fasudil hydrochloride pharmacologic postconditioning that alleviated acute myocardial ischemia/reperfusion injury (MI/RI) in rats,narrowed the scope of infacted myocardium,and inhibited cell apoptosis.Methods Ninety rats were randomly and averagely divided into 5 groups:sham group,ischemia/reperfusion (I/R) group,ischemic postconditioning (IPost) group,fasudil hydrochloride (FH) group,and FH and PI3K inhibitor (LY294002) (FH + I) group.The expressions of Rho associated coiled-coil forming protein kinase-1 (ROCK-1),Bcl-2,Bax,Caspase-3,Akt,and P-Akt in rat myocardial cells were determined.Results Compared to I/R group (ROCK1:2.94 ± 0.13),ROCK1 expression was not changed in IPost group (ROCK1:2.79 ± 0.11),FH group (ROCK1:2.83 ± 0.10),and FH + I group (ROCK1:2.85 ± 0.26).Compared to I/R group (Bcl-2:1.11 ± 0.12,P-Akt:1.09 ± 0.06,Bax:1.74 ± 0.06,and caspase-3:1.32 ± 0.12),the expressions of Bcl-2 and P-Akt in FH group (Bcl-2:1.76 ± 0.08,and P-Akt:1.73 ± 0.05) and IPost group (Bcl-2:1.74 ± 0.06,and P-Akt:1.37 ± 0.05) were all significantly higher than those in I/R group (P ＜ 0.05),while the expressions of Bax and caspase-3 in FH group (Bax:0.98 ±0.14,and caspase-3:0.97 ±0.06) and IPost group (Bax:0.97 ±0.11,and caspase-3:1.07 ±0.08) were all significantly lower than those in I/R group (P ＜0.05).Compared to FH group,the expressions of Bcl-2 and P-Akt in FH + I group (Bcl2:1.05 ±0.12,and P-Akt:1.21 ±0.06) were decreased (P ＜0.05),while the levels of Bax and caspase-3 (Bax:1.61 ±0.11,and caspase-3:1.42 ± 0.11) were increased (P ＜ 0.05).Conclusions The mechanism of FH postconditioning was associated with the inhibition of ROCK activity,and the activation of PI3K-Akt pathway.
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Objeetive To investigate protective effect of trimetazidine on myocardial ischemia/reperfusion injury (MIRI) in rats.Methods Forty Wistar rats were randomly divided into MIRI group (n =10 rats),trimetazidine high-dosage group (n =10 rats; 20 mg/kg),trimetazidine low-dosage group (n=10 rats; 10 mg/kg),and the normal control group (n =10 rats).After MIRI,hemodynamic changes were observed,the concentration of IL-6 and TNF-α was determined,and the cardiac muscle histology under the microscope was observed.Results Hemodynamic studies:Compared to the indices LVSP(198 ±35.5) mmHg,LVEDP (17 ±9.18) mmHg,+ dp/dt max (11050 ± 1517.4) mmHg/s,and-dp/dtmax (9175± 1900) mmHg/s] in the sham-operated group,the indices [LVSP (143 ± 24.5) mmHg,LVEDP (37.5 ±7.16)mmHg,+ dp/dtmax (7450 ± 1755.1) mmHg/s,and-dp/dtmax (6075 ± 1641) Hg/S] in the MIRI group,the indices [LVSP (154.5 ± 31.1) mmHg,LVEDP (31.3 ± 12.6) mmHg,± dp/dtmax (8527.7 ±2251.5) mmHg/s,and-dp/dtmax (6694 ± 2242.2) mmHg/s] in the trimetazidine low-dosage (10 mg/kg)group,the indices[LVSP (168.3 ± 17.6) mmHg,LVEDP (28 ± 10.05) mmHg,+ dp/dtmax (9213.6 ±1747) mmHg/s,and-dp/dtmax (7568 ± 1462.4) mmHg/s] in the trimetazidine high-dosage (20 mg/kg)group,left ventricular remodeling end diastolic pressure (LVEDP),left ventricular systolic pressure (LVSP),and left ventricular pressure maxial rate of rise and fall (± dp/dtmax) were significantly decreased.Compared to the MIRI group,LVSP and ± dp/dtmax in the trimetazidine high-dosage (20 mg/kg)group were significantly increased (P ＜ 0.01),and myocardial damage of MIRI group was more severe in microscope.Compared to the sham-operated group [IL-6 (2556.5 ± 662.9) ng/ml,and TNF-α (134 ± 73.7)ng/ml],the corresponding indices [IL-6 (3664.0 ± 995.7) ng/ml,and TNF-α (443 ± 22.1) ng/ml] in the MIRI group,[IL-6 (3692.8 1545.2) ng/ml,and TNF-α (295 ± 24.2) ng/ml] in the trimetazidiue low-dosage (10 mg/kg) group,and[IL-6(2654.8 ±681.7) ng/ml,and TNF-α(230 ±7.8) ng/ml]in the trimetazidine high-dosage (20 mg/kg) group,the levels of IL-6 and TNF-α were significantly increased.Compared to the MIRI group,the levels of IL-6 and TNF-α were significantly decreased in the trimetazidine high-dosage (20 mg/kg) group (P ＜ 0.01).Conclusions The high-dosage (20 mg/kg) of trimetazidine had a protective effect on myocardial ischemia-reperfusion injury.
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Objective To observe the protective effects of Diemailing Injection (DMLI) on myocardial ischemia-reperfusion injury in rats. Methods The myocardial ischemia-reperfusion model was induced by 30 min left anterior descending coronary occulusion and 24 h reperfusion in open-chest anesthetized rats. The changes of aspartate aminotransferase (AST), lactate dehydrogenase (LDH), MB isoenzyme of creatine kinase (CK-MB), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities and malondialdehyde (MDA) contents in serum, and prostacycline (PGI2) and thromboxane A2 (TXA2) levels in plasma were determined. Results In rats treated by DMLI (with dose of 2. 5, 5 and 10 mL ? kg-1 i. v. at 30 min after coronary occulusion), the myocardial ischemia size (MIS) was significantly reduced, the AST, LDH and CK-MB activities in serum and the TXA2 level in plasma were declined, while PGI2 level in plasma and PGI2/TXA2 ratio were increased significantly. In addition, the LPO content in serum declined, SOD and GSH-Px activities in serum were increased markedly. Conclusion DMLI has protective effects on myocardial ischemia-reperfusion injury through improving free radicals metabolism, decreasing TXA2 level in plasma, increasing PGI2 level in plasma and PGI2/TXA2 ratio.