Background Ouabain is a mammalian adrenocortical hormone that is involved in the pathogenesis of hypertension by inhibiting Na-K ATPase activity.It also participates in a variety of kinase-mediated signaling pathways associated with Na-K ATPase.Previous studies have shown that ouabain can cause cardiac remodeling independent of elevated blood pressure and that proliferating cell nuclear antigen （PCNA） plays a coordinating role for numerous proteins involved in multiple processes associated with DNA synthesis.Therefore,we hypothesized that ouabain might play a role in the cerebral cortex through signaling pathways independent of hypertension.And PCNA might be involved in this process.Methods Male Sprague-Dawley rats were treated with ouabain or with 0.9% nitric sodium as the control group.Systolic blood pressure was recorded weekly.After four weeks of treatment,morphological changes in the cerebral cortex were analyzed using light and transmission electron microscopy.The expression of PCNA in the cerebral cortex was evaluated by immunohistochemistry,real time quantitative PCR,and Western blotting.Results After 4-week treatment,there was no significant difference in systolic blood pressure compared with the control group,but both structural deterioration and up-regulated expression of PCNA in the brain was induced by ouabain treatment.Conclusions These results suggest that ouabain induces alterations in the brain structure,and this effect is independent of blood pressure.PCNA might be involved in the repair process of ouabain-induced brain damage.
You Beian Shen Lin Qiu Jie Liu Xiangju Zhao Shaohua Ji Xiang Wang Yan Gao Haiqing
Cardiac ischemia/reperfusion（I/R） injury is a critical condition,often associated with high morbidity and mortality.The cardioprotective effect of grape seed proanthocyanidin extracts（GSPE） against oxidant injury during I/R has been described in previous studies.However,the underlying molecular mechanisms have not been fully elucidated.This study investigated the effect of GSPE on reperfusion arrhythmias especially ventricular tachycardia（VT） and ventricular fibrillation（VF）,the lactic acid accumulation and the ultrastructure of ischemic cardiomyocytes as well as the global changes of mitochondria proteins in in vivo rat heart model against I/R injury.GSPE significantly reduced the incidence of VF and VT,lessened the lactic acid accumulation and attenuated the ultrastructure damage.Twenty differential proteins related to cardiac protection were revealed by isobaric tag for relative and absolute quantitation（iTRAQ） profiling.These proteins were mainly involved in energy metabolism.Besides,monoamine oxidase A（MAOA） was also identified.The differential expression of several proteins was validated by Western blot.Our study offered important information on the mechanism of GSPE treatment in ischemic heart disease.
LU Wei-daQIU JieZHAO Gai-xiaQIE Liang-yiWEI Xin-bingGAO Hai-qing
