论文部分内容阅读
超极化激活的环核苷酸门控通道(HCN通道)有四个亚型,分别为HCN1-4。HCN通道各亚型之间的基本结构相似,在许多组织中均有表达,其中以大脑和心脏组织中表达最为丰富。HCN通道既参与所在组织的正常生理功能,也与所在组织的病理状态密切相关。如神经损伤引起的神经源性疼痛常检测到HCN1通道表达量的增加,肥厚性心肌病和终末期心力衰竭等病理状态下常检测到心室肌细胞HCN4 mRNA及HCN2 mRNA表达增加。鉴于HCN通道与许多疾病密切相关,因此,以其为靶点来治疗相关疾病成为可能,但是由于HCN通道分布广泛,而目前该通道阻滞剂均为非选择性亚型抑制剂,临床应用时不可避免的引起副反应,因此发展选择性HCN通道亚型抑制剂就显得刻不容缓。本文就HCN通道抑制剂的研究发展做进一步探讨。
There are four subtypes of hyperpolarization-activated cyclic nucleotide gated channels (HCN channels), HCN1-4. The basic structure of each subtype of HCN channel is similar and expressed in many tissues, of which the most abundant is in brain and heart tissue. HCN channel both involved in the normal physiological function of the organization, but also closely related to the pathological state of the organization. Such as nerve injury caused by neuropathic pain HCN1 channel expression is often detected increased, hypertrophic cardiomyopathy and end-stage heart failure and other pathological conditions often detected in ventricular myocytes HCN4 mRNA and HCN2 mRNA expression increased. Given that HCN channels are closely related to many diseases, it is possible to treat these diseases as their targets. However, due to the wide distribution of HCN channels, the current blockers are all nonspecific subtype inhibitors. In clinical application Inevitably cause side effects, so the development of selective inhibitors of HCN channel subtype appears to be urgent. In this paper, HCN channel inhibitor research and development to further explore.