姜黄素对视网膜缺血再灌注损伤大鼠IL-17、IL-23、IL-1β、TNF-α及NF-κB表达的影响

Effects of Curcumin on the Expression of IL-17, IL-23, IL-1β and TNF-αin Rats with Retinal Ischemia-reperfusion Injury and the Expression of NF-κB

目的:研究不同剂量姜黄素对视网膜缺血再灌注损伤(RIRI)大鼠白细胞介素-17(IL-17)、白细胞介素-23(IL-23)、白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)及核转录因子-κB(NF-κB)表达的影响。方法:选取60只健康的SPF级雄性SD大鼠,将大鼠随机分为正常对照组(NC组)、模型组(M组)、姜黄素低剂量组(LC组)和姜黄素高剂量组(HC组),均为15只。M组、LC组和HC组大鼠的右眼均利用前房灌注法制备成RIRI模型,NC组进行正常喂养。模型制备前30 min和造模成功后每日定时给LC组和HC组腹腔分别注射30 mg/kg和120 mg/kg的姜黄素进行干预,NC组和M组则在同一时间腹腔注射适量的生理盐水。建模72h后显微镜下观察四组大鼠视网膜的组织形态,采用酶联免疫吸附法检测四组大鼠视网膜组织中IL-17、IL-23、IL-1β和TNF-α的水平,利用免疫组化法分析四组大鼠视网膜组织中NF-κB的表达情况。结果:NC组大鼠视网膜组织形态正常,M组、LC组和HC组大鼠视网膜组织形态均呈现出不同程度的病理性损伤,损伤程度排序为HC组<LC组<M组。M组IL-17、IL-23、IL-1β和TNF-α水平均高于HC组、LC组和NC组,LC组IL-17、IL-23、IL-1β和TNF-α水平均高于HC组和NC组,而HC组高于NC组(P<0.05)。M组NF-κB表达的OD值高于HC组、LC组和NC组,LC组NF-κB表达的OD值高于HC组和NC组,而HC组高于NC组(P<0.05)。结论:RIRI与炎症反应的增强及NF-κB的激活有关,姜黄素可有效降低RIRI的炎性因子水平,抑制NF-κB的激活,从而减轻RIRI的病理损伤和保护视网膜,且其保护作用在一定范围内与姜黄素的剂量呈正相关。

Objective: To study the effects of curcumin on the expression of interleukin-17 (IL-17), interleukin-23 (IL-23), interleukin-lp (IL-ip), tumor necrosis factor-a (TNF-a) and the expression of nuclear transcription factor-kB (NF-kB) in rats with retinal ischemia-reperfusion injury (RIRI). Methods: 60 healthy SPF male SD rats were selected, and they were randomly divided into normal control group (NC group), model group (M group), low-dose curcumin group (LC group) and high-dose curcumin group(HC group) according to random number table method, each group had 15. In M group, LC group and HC group, the RIRI model was built by the method of anterior chamber perfusion in the right eye, but the NC group was received normal feeding. Both LC group and HC group were given intraperitoneal injection of 30 mg/kg and 120 mg/kg cureumin for intervention at 30 minutes before model preparation and after successful modeling, NC group and M group were given the same amount of normal saline by intraperitoneal injection. After 72 hours of modeling, the morphology of retina in 4 groups of rats was observed under microscope. The levels of IL-17, IL-23, IL-lp and TNF-a in retinal tissue in 4 groups of rats were detected by enzyme-linked immunosorbent assay. The expression of nuclear factor-kB (NF-kB) in 4 groups of retina tissues was analyzed by immunohistochemistry. Result: The morphology of retina in NC group was nomial, but the morphology of retina in M group, LC group and HC group showed different degrees of pathological damage. The degree of injury was in the order of HC group<LC group<M group. The levels of IL-17, IL-23, IL-lp and TNF-a in M group were higher than those in HC group, LC group and NC group.The levels of IL-17, IL-23, IL-lp and TNF-a in LC group were higher than those in HC group and NC group, while those in HC group were higher than those in NC group (Pv0.05). The OD values of expression of NF-kB in M group were higher than those in HC group, LC group and NC group. The OD values of expression of N-kB in LC group were higher than those in HC group and NC group, while that of HC group was higher than that of NC group (P<0.05). Conclusion: The development of RIRI is related to the enhancement of inflammation and the activation of NF-kB. Curcumin could effectively reduce the level of inflammatory factors in RIRI, inhibit the activation of NF-kB, thus alleviate the pathological damage of RIRI and protect the retina. The protective effect of curcumin was positively related to the dosage of curcumin.