NLRP3信号通路相关抑制剂在眼病治疗中的应用

Application study of NLRP3 signalling pathway-related inhibitors in the treatment of ophthalmic diseases

炎症在众多疾病的发展中起着重要作用,而核苷酸结合寡聚化域样受体蛋白3(nucleotide binding oligomerization domain like receptors protein 3,NLRP3)信号通路是其中关键的一环。NLRP3可通过自组装后形成炎性小体激活半胱氨酸天冬氨酸蛋白水解酶-1,进而激活IL-1β和IL-18前体引发炎症;而马来酸胺乙基青蒿素、骨化三醇、非诺贝特、MCC950、白藜芦醇等药物则可通过抑制NLRP3信号通路的不同位点(如促进核转录因子κB、半胱氨酸天冬氨酸蛋白水解酶-1、NLRP3等)的表达以降低IL-18和IL-1β的表达,进而实现控制氧化应激和慢性炎症进展,最终实现治疗干眼、糖尿病视网膜病变和AMD等眼病的目的。目前NLRP3信号通路抑制剂治疗眼病的相关研究尚停留在较为早期的动物模型及体外实验,其于眼科疾病的应用研究有待进一步拓展。

Inflammation plays an important role in the development of numerous diseases,of which nucleotide binding oligomerization domain like receptors protein 3(NLRP3)signaling-pathway is a key component.NLRP3 can trigger inflammation by self-assembling to form inflammasome to activate casepase-1,which then activates IL-1βand IL-18 precursors.SM934,osteopontin,fenofibrate,MCC950 and resveratrol can reduce the expression of IL-18 and IL-1βby inhibiting the expression of different sites of the NLRP3 signaling pathway(e.g.NF-κB,casepase-1,NLRP3,etc.),thereby achieving the control of oxidative stress and the aim is to control oxidative stress and chronic inflammation,and ultimately to treat ophthalmic diseases such as dry eye,diabetic retionpathy and AMD.The research on NLRP3 signalling pathway inhibitors for ophthalmic diseases is still in the early stages of animal models and in vitro experiments,and its application in ophthalmic diseases needs to be further researcheded.