摘要
目的探究芍药二酮对链脲佐菌素诱导的糖尿病视网膜病变中视网膜血管炎性和血管通透性的影响及分子机制。方法采用腹腔注射链脲佐菌素(STZ)建立糖尿病视网膜病变大鼠模型,随机将SD大鼠分为对照组、模型组、芍药二酮低剂量组(25 mg/kg)、中剂量组(50 mg/kg)、高(100 mg/kg)剂量组。给药结束后,摘眼球取视网膜组织,通过HE染色观察视网膜组织形态,荧光素血管造影和伊文思蓝法分析视网膜血管通透性的改变,免疫组织化学检测大鼠视网膜组织中NLRP3的表达,qRT-PCR和Western blot检测大鼠视网膜组织中NLRP3炎症小体激活标志物Caspase-1、IL-1β、ASC和血管生成介质PECAM-1、ICAM-1、VEGF表达。结果芍药二酮抑制了糖尿病大鼠视网膜厚度和视网膜神经节细胞数量的减少,改善了视网膜结构疏松和细胞排列紊乱,降低了视网膜微血管的渗漏,减少了视网膜组织中NLRP3表达,下调炎症小体激活标志物和血管生成介质表达,抑制NLRP3炎症小体活化。结论芍药二酮能够减轻链脲佐菌素诱发的糖尿病视网膜血管炎性和血管通透性损伤,可能是通过抑制NLRP3炎症活性实现的。
Objective To explore the effect of paeoniflorin on retinal vascular inflammation and vascular permeability in diabetic retinopathy induced by streptozotocin and the molecular mechanism.Methods Intraperitoneal injection of streptozotocin(STZ)was used to establish a diabetic retinopathy rat model.SD rats were randomly divided into a control group,a model group,paeoniflorin low(25 mg/kg)and medium(50 mg/kg),high(100 mg/kg)-dose group.After the administration,the retinal tissues were removed from the eyeballs,and the retinal tissue morphology was observed by HE staining.Fluorescein angiography and Evans blue method were used to analyze the changes of retinal vascular permeability.The qRT-PCR and Western blot were used to detect the expression of NLRP3 inflammasome activation markers(Caspase-1,IL-1β,ASC)and angiogenesis mediators(PECAM-1,ICAM-1 and VEGF)in rat retina.Results Paeoniflorin inhibited the reduction of retinal thickness and the number of retinal ganglion cells in diabetic rats,improved retinal structural looseness and disordered cell arrangement,reduced retinal microvascular leakage,reduced the expression of NLRP3 in retinal tissue,down-regulated the expression of inflammation corpuscles activation markers and angiogenesis mediators,and inhibited the activation of NLRP3 inflammatory corpuscles.Conclusion Paeoniflorin can relieve the retinal vasculitis and vascular permeability damage induced by streptozotocin,possibly by inhibiting the inflammatory activity of NLRP3.
作者
冯雪艳
张慧芹
李幸
范玉香
刘时文
FENG Xue-yan;ZHANG Hui-qin;LI Xing;FAN Yu-xiang;LIU Shi-wen(Department of Ophthalmology,Cangzhou Central Hospital,Cangzhou 061000,China;School of Basic Medical Sciences,Hebei Medical University,Shijiazhuang 061000,China)
出处
《实用药物与临床》
CAS
2021年第7期585-590,共6页
Practical Pharmacy and Clinical Remedies
基金
河北省医学科学研究重点课题计划(20181500)。