姜黄素对视网膜缺血再灌注损伤大鼠视网膜组织结构及IL-23和IL-17表达的影响

Effects of curcumin on structure and the expression of interleukin-23 and interleukin-17 in rat retinal ischemia-reperfusion injury

目的:通过建立视网膜缺血再灌注损伤(retinal ischemiareperfusion injury,RIRI)模型,观察姜黄素对SpragueDawley(SD)大鼠视网膜组织结构及白细胞介素-23(interleukin-23,IL-23)和白细胞介素-17(interleukin-17,IL-17)表达的影响。方法:采用随机数字法将60只雄性SD大鼠随机分为正常对照组(normal control group,NCG)、模型组(model group,MG)、姜黄素低剂量组(low-dose curcumin group,LDCG)和姜黄素高剂量组(high-dose curcumin group,HDCG),每组15只。MG、LDCG、HDCG组SD大鼠右眼均采用前房灌注生理盐水升高眼压法建立RIRI模型。LDCG、HDCG组均于建模前30min和建模后每24h定时分别以20、100mg/kg的剂量腹腔注射姜黄素溶液。建模后72h作视网膜石蜡切片,采用HE染色观察各组视网膜组织结构及炎症细胞浸润程度。同时,提取视网膜分别作Westernblot、ELISA法检测和分析各组视网膜IL-23和IL-17的表达水平及变化情况。结果:光学显微镜观察发现NCG组视网膜结构正常,层次清楚,细胞排列均匀整齐,视网膜厚度正常,无炎症细胞浸润。MG、LDCG组视网膜组织水肿,各层排列紊乱,可见细胞空泡、核浓缩和炎症细胞浸润等病理改变。HDCG组视网膜组织结构与NCG组相似,视网膜组织结构完整,炎症反应相对较轻。Western-blot、ELISA法检测和分析均显示IL-23、IL-17在MG组的表达明显增强,与NCG组相比差异均具有显著统计学意义(P<0.01),但LDCG、HDCG组中IL-23、IL-17的表达较MG组明显降低,差异均有显著统计学意义(P<0.01)。结论:姜黄素可以减轻视网膜的炎症反应,保护视网膜组织结构;抑制视网膜IL-23、IL-17的表达,且呈剂量依赖性,这为姜黄素在亚急性期治疗RIRI提供了新的理论依据。

AIM： To observe the effect of curcumin on the retinal structure and the expressions of interleukin-23 （IL-23） and interleukin-17（IL-17） in the rat retina after retinal ischemia-reperfusion injury （RIRI）.METHODS：A total of 60 male Sprague-Dawley（SD） rats were randomly divided into normal control group（NCG）,model group（MG）,low-dose curcumin group （LDCG） and high-dose curcumin group （HDCG） （n=15 per group）.RIRI was generated by anterior chamber perfusion of normal saline to the right eye.Rats in LDCG and HDCG received an intraperitoneal injection of 20mg/kg/d and 100mg/kg/d curcumin respectively,at 30min before RIRI and once daily after RIRI.Retinal structure and inflammation were evaluated after hematoxylin and eosin-stained （HE） staining.Western-blot and enzyme-linked immunosorbent assay （ELISA） were used to measure the level of IL-23 and IL-17 expressions after RIRI.RESULTS： The retinal structure of NCG was normal.Retinal edema,empty spaces or loosely packed cells and inflammatory cell infiltration were observed in MG and LDCG groups,whereas the morphological changes in HDCG group were improved as compared to MG and LDCG groups.Western-blot assay and ELISA showed that IL-23 and IL-17 expressions increased significantly after RIRI （vs NCG,P〈0.01）.Moreover,curcumin reduced IL-23 and IL-17 expressions significantly （vs MG,P〈0.01）.CONCLUSION： Curcumin can inhibit leukocytes infiltration and improve the retinal pathologic changes.Furthermore,curcumin can reduce retinal IL-23 and IL-17 expressions significantly in a dose-dependent manner.