摘要目的:探讨高迁移率族蛋白B1（HMGB1）、半胱氨酸天冬氨酸蛋白酶1（caspase-1）、消皮素D在高海拔视网膜病变（HAR）发病机制中的作用。方法:实验研究。将12只8~10周龄雄性无特定病原体级c57BL/6J小鼠，采用随机数字表法均分为HAR组（构建HAR模型）和对照组（在常压常氧环境下）。采用苏木精-伊红（HE）染色方法观察小鼠视网膜的组织病理学形态，采用免疫荧光染色法检测HMGB1、caspase-1、消皮素D在小鼠视网膜中的分布及表达情况，采用免疫印迹法检测小鼠视网膜中HMGB1、caspase-1、消皮素D蛋白的相对表达量。采用独立样本 t检验进行统计学分析。 结果:HE染色结果显示，HAR组较对照组视网膜神经纤维层增厚，神经节细胞层细胞肿胀明显，内核层细胞间水肿，外核层层距明显增加，外丛状层疏松。免疫荧光染色结果显示，HAR组小鼠视网膜中HMGB1表达高于对照组，主要表达于神经节细胞层、内核层、外核层，HAR组小鼠视网膜中caspase-1、消皮素D表达高于对照组，主要表达于神经节细胞层、内丛状层、外丛状层。HAR组小鼠视网膜中HMGB1、caspase-1、消皮素D的免疫荧光值［（116.8±62.92）、（104.7±13.81）、（95.43±10.72）荧光强度单位（AFU）］高于对照组［（52.93±30.08）、（66.00±15.19）、（62.54±16.36）AFU］，差异均有统计学意义（均 P<0.05）。免疫印迹法检测结果显示，HAR组小鼠视网膜中HMGB1、caspase-1、消皮素D的条带灰度值（1.134±0.060、1.598±0.165、1.422±0.142）高于对照组（1.000±0.021、1.000±0.155、1.000±0.218），差异均有统计学意义（均 P<0.05）。 结论:HMGB1、caspase-1、消皮素D在HAR小鼠视网膜中表达显著增加，HMGB1通过caspase-1/消皮素D信号通路引起HAR小鼠视网膜组织细胞焦亡，导致视网膜结构破坏和HAR发生或发展。

abstractsObjective:To investigate the role of high mobility group protein B1 (HMGB1), cysteine aspartic protease 1 (caspase-1) and gasdermin D in the pathogenesis of high altitude retinopathy (HAR).Methods:This study is an experimental research. Twelve 8- to 10-week-old male c57BL/6J mice without a specific pathogen grade were randomly divided into the HAR group (HAR model) and control group (normal pressure and oxygen environment) according to the random number table method. Hematoxylin-eosin staining was used to observe the histopathological morphology of the mouse retina, and immunofluorescence staining was used to detect the distribution and expression of HMGB1, caspase-1 and gasdermin D in the mouse retina. The relative expression levels of HMGB1, caspase-1 and gasdermin D proteins in the mouse retina were detected by Western blot. Independent sample t test was used for statistical analysis.Results:Hematoxylin-eosin staining showed that compared with the control group, the retinal nerve fiber layer in the HAR group was thickened, the ganglion cell layer was swollen significantly, the intercellular edema in the inner nuclear layer was increased significantly, and the outer nuclear layer distance was loosened. Immunofluorescence staining results showed that HMGB1 expression in the retina of mice in the HAR group was higher than that in the control group, and it was mainly in the ganglion cell layer, inner nuclear layer and outer nuclear layer. Caspase-1 and gasdermin D expressions in the retina of mice in the HAR group were higher than those in the control group, and they were mainly in the ganglion cell layer, inner plexiform layer and outer plexiform layer. The immunofluorescence values of HMGB1, caspase-1 and gasdermin D in the HAR group [(116.8±62.92), (104.7±13.81) and (95.43±10.72) arbitrary fluorescence units] were higher than those in the control group [(52.93±30.08), (66.00±15.19) and (62.54±16.36) arbitrary fluorescence units]. The differences were statistically significant (all P<0.05). The results of the Western blot test showed that the gray band values of HMGB1, caspase-1 and gasdermin D proteins in the retina of HAR group (1.134±0.060, 1.598±0.165 and 1.422±0.142) were higher than those in the retina of control group (1.000±0.021, 1.000±0.155 and 1.000±0.218), with statistically significant differences (all P<0.05). Conclusions:The expressions of HMGB1, caspase-1 and gasdermin D were significantly increased in the retina of HAR mice. HMGB1-mediated pyroptosis in the retinal tissue of HAR mice through the caspase-1/gasdermin D signaling pathway led to retinal structure destruction and the occurrence or development of HAR.