中文摘要
缺血性视网膜病变伴发的视网膜水肿是造成患者视力损害的重要因素,而Müller细胞上水通道蛋白4(AQP4)与内向整流钾通道(Kir4.1)水钾转运功能失调是视网膜水肿形成的重要病理机制。本课题组经长期临床实践提出"目络瘀阻"病机理论假说,在此理论指导下研发出活血通络利水方,并在该复方治疗缺血性视网膜水肿有效的基础上,体内外实验相结合,从AQP4/Kir4.1失衡角度探讨缺血性视网膜水肿形成机理,研究对AQP4具有调控作用的PKC-MAPK信号通路中关键蛋白的变化;分析视网膜病变组织中Na+-K+-ATP酶、兴奋性氨基酸、炎性因子、氧化应激与AQP4之间的内在联系。从多角度、多层次阐释"目络瘀阻"病机理论的微观辨证特征,探索能够反映虚、瘀、毒、水等病理因素之间相互兼杂的微观证侯指标群,进一步探讨活血通络利水中药复方治疗缺血性视网膜疾病和视网膜水肿的作用靶点和可能作用机制,为新药开发奠定基础。
英文摘要
The retinal edema associated with ischemic retinal diseases play an important role in severe visual impairment. Modern researchs find that the transport dysfunction of the water and potassium of müller cell is one of the important pathophysiological mechanisms for the formation of the retinal edema. Based on years of experience on clinical practice, the workgroup put forward a pathogenesis theory of ocular collateral stasis syndrome. Therefore in virtue of the guidance of theory, an effective Chinese herbal compound (i.e. Huoxuetongluolishui recipe) was developed. Based on excellent therapeutic effect of the herbal compositions, we conduct this study to investigate the formation mechanism of ischemic retinal edema through the malfunction of aquaporin 4 and Kir 4.1, and the role of their signal transduction pathways (i.e. PKC-ERK1/2 and p38 MAPKs pathway) involved in retinal edema. The study also analyzes the inter-relationships among the aquaporin 4, Na/K-ATPase, inflammatory factors, oxidative stress and excitatory amino acids in the ischemicl retinal tissues. Based on researches mentioned above, the analysis is carried on in multi-angles and multi-levels so as to characterize the micro syndrome of "ocular collateral stasis syndrome" theory, and explore setting up the auxiliary microcosmic diagnostic index system which reflects the complex interaction and transformation between deficiency, blood-stasis, toxin and fluid retention. Furthermore, we investigate the protective effects of Huoxuetongluolishui recipe on ischemic retinal disease and further explore its possible acting mechanism and underlying targets in order to develop new drugs for the treatment of ischemic eye disease.
