RESUMO
Aim To investigate whether pioglitazone has protective effect against glutamate induced neurotoxicity in cultured cortical neurons and its possible molecular mechanisms underlying pioglitazone's neuroprotective effects.Methods The cortical neurons were taken from newborn rats and used for experiments 7 days after culture.The neurons were randomly divided into control group;glutamate group; glutamate+piogli-tazone group;glutamate+SP600125 group;SP600125 group.Cell viability was determined by MTT.The morphology change of neurons was observed under a fluorescence microscope with fluorescence dye Hoechst 33258.Immunostaining was used to investigate the expression of phospho-ATF2 in neuronal cells.Western blot was performed to investigate the protein level of phospho-JNK1 and total JNK1.Results Pioglitazone markedly reduced the damage of cortical neurons caused by glutamate.Pioglitazone also significantly inhibited glutamate induced up-regulation of phospho-JNK1 protein level and phospho-ATF2 expression.SP600125, an inhibitor of JNK, antagonized the toxicity induced by glutamate.Conclusions Pioglitazone can protect cultured cortical neurons from glutamate induced damage.The protective effect of pioglitazone appears to be associated with inhibiting the c-Jun N-terminal protein kinase signaling pathway.
RESUMO
AIM To study the relation between the antiarrthymic effect and the inhibition of slow reaction cardiomyocyte of ethacizine(EC). METHODS The beating rate and action potentials of cultured slow response cardiomyocyte from neonatal rats was recorded. RESULTS EC 0 1～5 0 ?mol?L -1 produced a concentration dependent suppressing effect on spontaneous beating rate of cultured cardiac cells with IC 50 of 0 17 ?mol?L -1 and the maximal inhibitory rate was 52%.The steady state of inhibition to beating rate was achieved after adding EC for 15～30 min. The effective inhibition of beating rate by EC lasted for over 1 h.As EC 2 5 ?mol?L -1 depressed beating rate to the steady state ,effects of CaCl 2 2 mmol?L -1 and Iso 1 ?mol?L -1 on beating rate were partially reduced,and the effect of aconitine 0 2 mg?L -1 was abolished. EC 0 3～2 5 ?mol?L -1 pruduced the concentration dependent depression on APA,V max ,OS,SP 4 and MDP,and prolongation of SCL of the slow response action potentials.APD 90 was also lengthened at the concentration of EC 0 9～2 5 ?mol?L -1 . CONCLUSIONS The effective depression of EC on abnormal automaticity and conductance of the slow response cardiomyocyte in heart ischemic zone may be an important mechanism for its effective termination on some arrhythimas.EC may depress Ca 2+ ,especially Na + currents on slow response cardiomyocyte.