曲安奈德对自发性高血压大鼠视网膜P2X7R/NLRP3通路及眼底血管病变的影响  

Effects of triamcinolone acetonide on P2X7R/NLRP3 pathway and fundus angiopathy in spontaneously hypertensive rats

作　　者：田甜[1] 吴凌 徐丽[1] TIAN Tian;WU Ling;XU Li(Department of Ophthalmology,the Fourth People’s Hospital of Shenyang,Shenyang 110031,Liaoning Province,China)

机构地区：[1]沈阳市第四人民医院眼科,辽宁省沈阳市110031

出　　处：《眼科新进展》2020年第12期1125-1129,共5页Recent Advances in Ophthalmology

基　　金：沈阳市卫生健康委员会2018年科研课题计划项目(编号19-112-4-070)。

摘　　要：目的探讨曲安奈德(TA)对自发性高血压(spontaneously hypertensive,SHR)大鼠视网膜嘌呤能2X7受体(purinergic 2X7 receptor,P2X7R)/核苷酸结合寡聚化结构域受体蛋白3(nucleotide-binding and oligomerization domain-like receptor protein 3,NLRP3)通路蛋白表达及对眼底血管病变的影响。方法将40只双眼均有视网膜病变的SHR京都维斯特(WKY)大鼠随机分为模型组(SHR组)及TA低(20 g·L-1)、中(40 g·L-1)、高(80 g·L-1)剂量组,另取10只健康WKY大鼠作为空白组(Control组);TA低、中、高剂量组球结膜下四个方向分别注射相应剂量TA各10μL,Control组和SHR组注射等体积生理盐水,每7 d 1次;给药2周后,检测各组大鼠血压、左眼眼压及各组大鼠眼底视网膜形态,利用彩色超声多普勒检查大鼠视网膜中央动脉(central retinal artery,CRA)血流速度和视网膜中央静脉(central retinal vein,CRV)血流速度。观察各组大鼠视网膜结构、微血管变化,并检测视网膜毛细血管密度;行Western blot检测视网膜通路P2X7、NLRP3、肿瘤坏死因子α(TNF-α)、白细胞介素-6(IL-6)蛋白相对表达水平。结果与Control组相比,SHR组大鼠视网膜毛细血管闭塞及黄斑水肿等病理损伤明显,收缩压、舒张压、平均血压、眼压及P2X7、NLRP3、TNF-α、IL-6各蛋白相对表达水平均升高(均为P<0.05),毛细血管密度及CRA、CRV血流速度均降低(均为P<0.05);与SHR组相比,TA低、中、高剂量组视网膜毛细血管闭塞及黄斑水肿等病理损伤程度有所减轻,P2X7、NLRP3、TNF-α、IL-6各蛋白相对表达水平均降低(均为P<0.05),毛细血管密度及CRA、CRV血流速度均升高(均为P<0.05),且TA各剂量组呈剂量依赖性;与SHR组相比,TA各剂量组大鼠收缩压、舒张压、平均血压、眼压均无明显变化(均为P>0.05)。结论TA可能通过P2X7R/NLRP3通路抑制炎症反应,进而改善SHR大鼠眼底血管病变。Objective To investigate the effects of triamcinolone acetonide(TA)on the expression of retinal purinergic 2X7 receptor(P2X7R)/nucleotide binding oligomerization domain-like receptor pathway(3NLRP3)protein in the spontaneously hypertensive(SHR)rats and fundus angiopathy.Methods Forty SHR Wistar-Kyoto(WKY)rats with retinopathy in both eyes were randomly divided into model group(SHR),low TA(20 g·L-1),medium TA(40 g·L-1)and high TA(80 g·L-1)dose groups,and another 10 healthy WKY rats were taken as Control group.The low,medium and high TA dose groups were injected with 10μL of corresponding dose of TA through subconjunctival,respectively,and the Control group and SHR group were injected with the same amount of normal saline,once every 7 days.After 2 weeks of administration,the blood pressure of each group was measured,the intraocular pressure in the left eye was measured with tonometer,and the retinal morphology of each group was examined by slit lamp.The mean flow velocity of central retinal artery(CRA)and central retinal rein velocity(CRV)in rats were examined by color Doppler ultrasonography.Rats were killed,and the retina of the left eye was taken out,and then the changes of retinal structure and microvasculature were observed by hematoxylin eosin staining(HE)and the density of retinal capillary was measured.The relative expression levels of P2X7,NLRP3,tumor necrosis factor-α(TNF-α)and interleukin 6(IL-6)proteins in the retinal pathway was detected by Western blot.Results Compared with the Control group,systolic pressure,diastolic pressure,mean blood pressure,intraocular pressure,the pathological damage degrees of retinal capillary occlusion and macular edema,the relative expression levels of P2X7,NLRP3,TNF-αand IL-6 proteins in SHR group were higher(all P<0.05),and the capillary density,CRA and CRV were lower(all P<0.05).Compared with SHR group,the pathological damage degrees of capillary occlusion and macular edema,the relative expression levels of P2X7,NLRP3,TNF-αand IL-6 proteins in low,medium and hig

关 键 词：曲安奈德 自发性高血压 视网膜嘌呤能2X7受体/核苷酸结合寡聚化结构域样受体通路 眼底血管病变 

分 类 号：R774[医药卫生—眼科]