Quercetin protects the retina by reducing apoptosis due to ischemia-reperfusion injury in a rat model

Purpose: This study aimed to investigate the effect of quercetin on apoptotic cell death induced by ischemia-reperfusion (I/R) injury in the rat retina. Methods: Twenty-four rats were divided into four equal groups: control, ischemic, solvent, and quercetin. I/R injury was achieved by elevating the intraocular pressure above the perfusion pressure. Intraperitoneal injections of 20 mg/kg of quercetin and dimethyl sulfoxide (DMSO) were performed in the quercetin and solvent groups, respectively, immediately prior to I/R injury, and the researchers allowed for the retinas to be reperfused. Forty-eight hours after injury, the thicknesses of the retinal ganglion cell layer (RGCL), inner nuclear layer (INL), inner plexiform layer (IPL), outer plexiform layer (OPL), and outer nuclear layer (ONL) were measured in all groups. Moreover, the numbers of terminal deoxynucleotidyl transferase dUTP nick-end-labeled [TUNEL (+)] cells and caspase-3 (+) cells in both INL and ONL were evaluated in all groups. Results: The administration of quercetin was found to reduce the thinning of all retinal layers. The mean thickness of INL in the quercetin and ischemic groups was 21 ± 5.6 µm and 16 ± 6.4 µm, respectively (P<0.05). Similarly, the mean thickness of ONL in the quercetin and ischemic groups was 50 ± 12.8 µm and 40 ± 8.7 µm, respectively (P<0.05). The antiapoptotic effect of quercetin in terms of reducing the numbers of both TUNEL (+) cells and caspase-3 (+) cells was significant in INL. The mean number of TUNEL (+) cells in INL in the ischemic and quercetin groups was 476.8 ± 45.6/mm2 and 238.72 ± 251/mm2, respectively (P<0.005). The mean number of caspase-3 (+) cells in INL of ischemic and quercetin groups was 633.6 ± 38.7/mm2 and 342.4 ± 36.1/mm2, respectively (P<0.001). Conclusion: The use of quercetin may be beneficial in the treatment of retinal I/R injury because of its antiapoptotic effect on the retinal layers, particularly in INL.

研究目的：本研究旨在探讨槲皮素（quercetin）对大鼠视网膜缺血再灌注（ischemia-reperfusion, I/R）损伤诱导的细胞凋亡的影响。
方法：将24只大鼠均分为四组：对照组、缺血组、溶剂对照组与槲皮素干预组。通过升高眼内压至灌注压以上的方式构建视网膜I/R损伤模型。槲皮素干预组与溶剂对照组分别于I/R损伤术前即刻腹腔注射20 mg/kg槲皮素与二甲基亚砜（dimethyl sulfoxide, DMSO），随后恢复视网膜血流灌注。造模48小时后，对所有组别大鼠的视网膜神经节细胞层（retinal ganglion cell layer, RGCL）、内核层（inner nuclear layer, INL）、内丛状层（inner plexiform layer, IPL）、外丛状层（outer plexiform layer, OPL）以及外核层（outer nuclear layer, ONL）的厚度进行测量。此外，对所有组别内核层与外核层中末端脱氧核苷酸转移酶dUTP缺口末端标记阳性（terminal deoxynucleotidyl transferase dUTP nick-end-labeled positive, TUNEL(+)）细胞与半胱氨酸天冬氨酸蛋白酶-3阳性（caspase-3(+)）细胞的数量进行计数分析。
结果：槲皮素干预可减轻所有视网膜层的变薄程度。槲皮素干预组与缺血组的内核层平均厚度分别为21 ± 5.6 µm与16 ± 6.4 µm（P<0.05）。同理，槲皮素干预组与缺血组的外核层平均厚度分别为50 ± 12.8 µm与40 ± 8.7 µm（P<0.05）。槲皮素的抗凋亡作用在降低内核层中TUNEL(+)细胞与caspase-3(+)细胞数量方面效果显著。缺血组与槲皮素干预组内核层的TUNEL(+)细胞平均数量分别为476.8 ± 45.6/mm²与238.72 ± 251/mm²（P<0.005）；缺血组与槲皮素干预组内核层的caspase-3(+)细胞平均数量分别为633.6 ± 38.7/mm²与342.4 ± 36.1/mm²（P<0.001）。
结论：槲皮素可通过对视网膜各层发挥抗凋亡作用，尤其作用于内核层，因此有望用于视网膜I/R损伤的治疗。