芍药苷通过调控NLRP3炎症小体保护视网膜缺血性损伤  

The protective effect of paeoniflorin in retina ischemia animal model through regulation of NLRP3 inflammasomes

作　　者：杨佩瑶 赵军[2] 张娟美[2] 高云霞[2] 战伟娇 王赟[2] 王强[2] 薛友余 Yang Peiyao;Zhao Jun;Zhang Juanmei;Gao Yunxia;Zhan Weijiao;Wang Yun;Wang Qiang;Xue Youyu(Qingdao University Medical College,Qingdao 266075,China;Department of Ophthalmology,Linyi People's Hospital,Linyi 266071,China)

机构地区：[1]青岛大学医学院,266075 [2]山东省临沂市人民医院眼科,266071

出　　处：《中华实验眼科杂志》2018年第12期920-924,共5页Chinese Journal Of Experimental Ophthalmology

摘　　要：目的 通过视网膜缺血性损伤动物模型探讨芍药苷保护视网膜的作用机制.方法 无特定病原体动物(SPF)级雄性Wistar大鼠54只,按照随机数字表法分为正常对照组、模型对照组和芍药苷组.模型对照组和芍药苷组采用右眼前房灌注方法建立大鼠视网膜缺血动物模型,左眼为对照眼不作处理;芍药苷组造模后每日大鼠腹腔内注射芍药苷5mg/kg.分别采用OCT及视网膜电图(ERG)检测各组大鼠视网膜神经纤维层+视网膜神经节细胞层+内丛状层(NGI)厚度和电生理改变.于造模后7 d采用荧光金逆行标记视网膜神经节细胞(RGCs),并在造模后14 d取出大鼠视网膜行RGCs铺片和RGCs计数.Western blot法检测各组视网膜NLRP3、凋亡相关微粒蛋白(ASC)、cleaved caspase.1(c.caspase1)、白细胞介素(IL).18、IL.1β蛋白表达.结果 3个组大鼠造模后14 d视网膜NGI厚度总体比较,差异有统计学意义(F=45.85,P<0.01).其中模型对照组视网膜NGI厚度为(58.2±1.7)μm,显著低于正常对照组的(84.8±1.9)μm和芍药苷组的(71.1±2.4)μm,差异均有统计学意义(均P<0.05).造模后14 d,各组a波、b波振幅总体比较,差异均有统计学意义(F=48.87、71.07,均P<0.001).芍药苷组和正常对照组a、b波振幅较模型对照组明显升高,差异均有统计学意义(均P<0.05).模型对照组RGCs计数显著低于芍药苷组和正常对照组,差异均有统计学意义(均P<0.05).各组NLRP3、ASC、c.caspase1、IL.18和IL.1β总体比较,差异均有统计学意义(F=78.94、197.5、67.77、132.2、49.33,均P<0.01).模型对照组NLRP3、ASC、c.caspase1、IL.18和IL.1β的相对表达量显著高于正常对照组和芍药苷组,差异均有统计学意义(均P<0.01).结论 芍药苷可以通过抑制NLRP3炎症小体信号通路延缓视网膜损伤,为缺血性视网膜病变的治疗提供新的途径.Objective To investigate the mechanisms of paeoniflorin in protection of retinal ischemia injury. Methods Fifty-four male specefic pathogen free (SPF)degree Wistar rats were randomly divided into normal control group,model control group and paeoniflorin group.Retinal ischemia injury was induced by raising the intraocular pressure of right eyes of rats to 110 mmHg for 30 minutes.The rats of paeoniflorin group were administrated through intraperitoneal injection of 5mg/kg paeoniflorin each day for 14 days.OCT and electroretinogram (ERG)were performed to detect the thickness of retinal nerve fiber layer+retinal ganglion cell layer+inner plexiform layer (NGI) and electrophysiological changes of retina,respectively.Retrograde labelling of retinal ganglion cells (RGCs)was used to evaluate the survival number of RGCs.Western blot analysis was used to detect NLRP3,apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC),cleaved caspase 1(c-caspase 1), IL-18,and IL-1β expression.The use and care of animals complied with the statement of the Association for Research in Vision and Ophthalmology (ARVO)and Regulations for the Administration of Affair Concerning Experimental Animals by State Science and Technology Commission.Results The thickness of retinal NGI in model control group was (58.2±1.7)μm,which was significantly lower than (84.8±1.9)μm in normal control group and (71.1±2.4)μm in paeoniflorin group (both at P<0.05).The amplitudes of A and B waves in paeoniflorin group and normal control group were significantly higher than those in model control group (both at P<0.05).The number of RGC in model control group was significantly lower than that in paeoniflorin group and normal control group (both at P<0.05).The relative expressions of NLRP3,ASC,c-caspase 1,IL-18and IL-1β in model control group were significantly higher than those in normal control group and paeoniflorin group (all at P<0.05).Conclusions The paeoniflorin can prevent retinal ischemia induced injury of t

关 键 词：芍药苷 视网膜缺血 高眼压 NLRP3炎症小体 

分 类 号：R77[医药卫生—眼科]