目的:探讨氯氨酮减轻高血糖加重脑缺血损伤的机制.方法:在正常血糖、高血糖以及氯氨酮干预条件下,制作大鼠全脑缺血15 m in,再灌注0.5,1和3 h模型.通过免疫组化和免疫印迹技术对比研究细胞外信号调节激酶1/2(ERK1/2)的磷酸化,同时采用...目的:探讨氯氨酮减轻高血糖加重脑缺血损伤的机制.方法:在正常血糖、高血糖以及氯氨酮干预条件下,制作大鼠全脑缺血15 m in,再灌注0.5,1和3 h模型.通过免疫组化和免疫印迹技术对比研究细胞外信号调节激酶1/2(ERK1/2)的磷酸化,同时采用末端脱氧核苷酸转移酶介导的dUTP原位切口末端标记方法观察神经细胞凋亡.结果:正常血糖组大鼠全脑再灌注0.5 h扣带皮质和海马CA1及CA3区的ERK1/2磷酸化明显增加;在高血糖组缺血再灌注后0.5 h,扣带皮质和海马CA3区的ERK1/2磷酸化明显高于正常血糖组,持续到再灌注后的3 h;氯氨酮组可见由高血糖诱导的ERK1/2磷酸化被抑制.同时,磷酸化ERK1/2的程度与脑组织损伤结果一致.结论:高血糖可通过ERK1/2信号转导通路加重缺血性脑损伤,氯氨酮通过阻断NMDA受体,改善钙离子异常而抑制高血糖介导的ERK1/2磷酸化,从而减轻高血糖加重缺血性脑损伤.展开更多
Intrahepatic cholangiocarcinomas (ICC) are neoplasms that originate from cholangiocytes and can occur at any level of the biliary tree. Surgical resection is the current therapy of choice for this highly aggressive ca...Intrahepatic cholangiocarcinomas (ICC) are neoplasms that originate from cholangiocytes and can occur at any level of the biliary tree. Surgical resection is the current therapy of choice for this highly aggressive cancer. However, the 5-year survival still is poor, with high recurrence rates. Due to the intrahepatic growth a signifi cant proportion of patients present with advanced disease and are not candidates for curative surgery or transplantation. The existing palliative options are of limited benefit and there is a great necessity for novel therapeutic options. In this article we review the role of the phosphoinositide 3-kinase(PI3K)/ AKT and extracellular regulated kinase (ERK) signaling pathways in ICC and present new data on the prognostic value of these protein kinases. Finally, we discuss future upcoming therapeutic options based on targeting these signaling pathways.展开更多
文摘Intrahepatic cholangiocarcinomas (ICC) are neoplasms that originate from cholangiocytes and can occur at any level of the biliary tree. Surgical resection is the current therapy of choice for this highly aggressive cancer. However, the 5-year survival still is poor, with high recurrence rates. Due to the intrahepatic growth a signifi cant proportion of patients present with advanced disease and are not candidates for curative surgery or transplantation. The existing palliative options are of limited benefit and there is a great necessity for novel therapeutic options. In this article we review the role of the phosphoinositide 3-kinase(PI3K)/ AKT and extracellular regulated kinase (ERK) signaling pathways in ICC and present new data on the prognostic value of these protein kinases. Finally, we discuss future upcoming therapeutic options based on targeting these signaling pathways.
