目的：探讨高原缺氧环境对大鼠视网膜损伤的影响及氧化应激相关指标水平的变化。

方法：将24只健康雄性SD大鼠随机分为平原组和高原组，每组12只24眼。平原组饲养于常氧环境SPF级动物实验中心，高原组置于特殊环境人工舱(模拟海拔6 000 m)7 d。采用光学相干断层扫描(OCT)检测视网膜结构层次并量化视网膜厚度； 苏木精-伊红(HE)染色观察视网膜病理形态变化； 免疫荧光(IF)检测视网膜组织低氧诱导因子-1α(HIF-1α)表达； 透射电子显微镜(TEM)扫描观察视网膜神经节细胞(RGCs)超微结构； 酶联免疫吸附法(ELISA)检测大鼠视网膜组织内丙二醛(MDA)、总超氧化物歧化酶(T-SOD)和还原型谷胱甘肽(GSH)水平； 采用2，7-二氯荧光素二乙酸酯(DCFH-DA)荧光探针法检测大鼠视网膜组织内活性氧(ROS)强度。

结果：高原组大鼠OCT显示视网膜结构紊乱，内、中环厚度增加，外环厚度减少(均P<0.05)； HE染色显示视网膜各层结构出现不同程度损伤，层次界限模糊，RGCs排列疏松并见部分细胞坏死； IF提示高原组内核层HIF-1α表达升高(P<0.01)； TEM显示高原组RGCs线粒体肿胀、嵴紊乱、基质电子密度减低； ELISA及荧光探针法结果显示，高原组大鼠视网膜组织中MDA含量和ROS荧光强度显著升高，T-SOD及GSH水平则降低(均P<0.05)。

结论：暴露高原环境下大鼠视网膜出现明显的形态结构损伤和超微结构变化，氧化应激水平显著升高，提示氧化应激可能在高原缺氧所致视网膜损伤中发挥重要作用。

METHODS: Twenty-four healthy male Sprague-Dawley(SD)rats were randomly divided into a plain group and a high-altitude group, with 12 rats(24 eyes)in each group. Rats in the plain group were housed under normoxic conditions in an SPF-grade animal facility, whereas rats in the high-altitude group were placed in a special environmental chamber simulating an altitude of 6 000 m for 7 d. Optical coherence tomography(OCT)was used to assess retinal layer architecture and quantify retinal thickness. Hematoxylin-eosin(HE)staining was performed to observe retinal histopathological changes. Immunofluorescence(IF)was used to detect the expression of hypoxia-inducible factor-1α(HIF-1α)in retinal tissue. Transmission electron microscopy(TEM)was applied to examine the ultrastructure of retinal ganglion cells(RGCs). Enzyme-linked immunosorbent assay(ELISA)was used to measure the levels of malondialdehyde(MDA), total superoxide dismutase(T-SOD), and reduced glutathione(GSH)in retinal tissue. In addition, intracellular reactive oxygen species(ROS)levels in retinal tissue were assessed using the 2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA)fluorescent probe.

RESULTS: OCT examination revealed disorganized retinal architecture in the high-altitude group, with increased inner and middle ring thickness and decreased outer ring thickness compared with the plain group(all P<0.05). HE staining showed varying degrees of retinal layer damage, blurred layer boundaries, loosely arranged RGCs, and partial cellular necrosis in the high-altitude group. IF analysis demonstrated significantly increased HIF-1α expression in the inner nuclear layer of the high-altitude group(P<0.01). TEM revealed mitochondrial swelling, disrupted cristae, and reduced matrix electron density in RGCs of the high-altitude group. ELISA and fluorescence probe assays showed significantly elevated MDA levels and ROS fluorescence intensity, accompanied by decreased T-SOD and GSH levels in the retinal tissue of the high-altitude group(all P<0.05).

CONCLUSION: Exposure to a high-altitude hypoxic environment induces marked morphological and ultrastructural damage in the rat retina and significantly enhances oxidative stress, suggesting that oxidative stress may play a critical role in retinal injury induced by high-altitude hypoxia.