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Objective:To study protective effects of ranolazine preconditioning on myocardial ischemia reperfusion in-jury(MIRI)in rats.Methods:A total of 32 SD rats were randomly and equally divided into sham operation group, ischemia/reperfusion(I/R)group,low dose ranolazine group(low dose group)and high dose ranolazine group (high dose group).HR,SBP,DBP,left ventricular systolic pressure(LVSP),left ventricular diastolic pressure (LVDP),left ventricular pressure maximum rate of rise(+dp/dtmax),left ventricular pressure maximum rate of de-cline(-dp/dtmax),levels of CK-MB,LDH and cTnI,severity of myocardial infarction and ATP concentration were measured and compared among all groups.Results:Compared with sham operation group,there were significant re-ductions in LVSP[(119.35 ± 5.00)mmHg vs.(92.68 ± 2.95)mmHg vs.(100.60 ± 3.12)mmHg vs.(112.22 ± 3.69)mmHg],LVDP[(24.78 ± 1.71)mmHg vs.(17.26 ± 1.69)mmHg vs.(19.25 ± 1.05)mmHg vs.(22.18 ± 1.55)mmHg],+dp/dtmax[(3736 ± 102.37)mmHg/s vs.(3115 ± 112.72)mmHg/s vs.(3338 ± 51.88)mmHg/s vs.(3446 ± 37.99)mmHg/s],-dp/dtmax[(3634 ± 102.51)mmHg/s vs.(3015 ± 127.00)mmHg/s vs.(3239 ±37.36)mmHg/s vs.(3349 ± 45.49)mmHg/s]and ATP concentration[(22.54 ± 1.52)nmol/mg vs.(14.08 ± 1.80) nmol/mg vs.(16.88 ± 0.74)nmol/mg vs.(19.34 ± 0.88)nmol/mg],and significant rise in levels of CK-MB [(490.88 ± 168.04)U/L vs.(1259.0 ± 78.02)U/L vs.(1127.9 ± 127.23)U/L vs.(956.62 ± 105.22)U/L], LDH[(1494.9 ± 174.84)U/L vs.(2657.6 ± 104.33)U/L vs.(2293.9 ± 99.58)U/L vs.(1932.6 ± 134.25)U/L]and cTnI[(1.03 ± 0.14)ng/ml vs.(10.62 ± 1.34)ng/ml vs.(6.97 ± 1.32)ng/ml vs.(4.87 ± 0.79)ng/ml] in I/R group,low dose group and high dose group,P<0.01 all.Compared with I/R group,there were significant rise in LVSP,LVDP,+ dp/dtmax,-dp/dtmaxand ATP concentration,and significant reductions in levels of CK-MB,LDH and cTnI and MI severity[(0.5289 ± 0.0223)vs.(0.4887 ± 0.0089)vs.(0.4438 ± 0.0154)]in low dose group and high dose group(P<0.05 or <0.01),and those of high dose group were significantly better than those of low dose group(P< 0.05 or < 0.01).Conclusion:Ranolazine preconditioning possesses significant protective effect on MIRI,and it's dose-dependent.
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<p><b>BACKGROUND</b>Y-27632 is a specific inhibitor of Rho-associated coiled kinase (ROCK) and has been shown to promote the survival and induce the differentiation of a variety of cells types. However, the effects of Y-27632 on adult human adipose tissue-derived stem cells (ADSCs) are unclear. This study aimed to investigate the effects of Y-27632 on the neuronal-like differentiation of ADSCs.</p><p><b>METHODS</b>ADSCs were isolated from women undergoing plastic surgery and cultured. ADSCs were treated with different doses of Y-27632 and observed morphological changes under microscope. The expression of nestin, neuron specific enolase (NSE) and microtubule-associated protein-2 (MAP-2) in ADSCs treated with Y-27632 was detected by immunocytochemistry and Western blotting analysis.</p><p><b>RESULTS</b>Y-27632 had the potency to induce neuronal-like differentiation in ADSCs in a dose-dependent manner. Moreover, the differentiation induced by Y-27632 was recovered upon drug withdraw. ADSCs treated with Y-27632 expressed neuronal markers such as NSE, MAP-2 and nestin while untreated ADSCs did not express these markers.</p><p><b>CONCLUSION</b>Selective ROCK inhibitor Y-27632 could potentiate the neuronal-like differentiation of ADSCs, suggesting that Y-27632 could be utilized to induce the differentiation of ADSCs to neurons and facilitate the clinical application of ADSCs in tissue engineering.</p>