关键词: 模拟失重, 角膜, 氧化应激, 炎性反应

Abstract: Objective　To observe the effects of long-term simulated weightlessness induced by tail suspension on the rat cornea, and to explore the molecular mechanisms underlying corneal injury. Methods　Twenty-four SD rats were randomly divided into control group, 4-week tail suspension group and 8-week tail suspension group, with 8 rats per group. After model establishment, tear secretion was measured by the phenol red thread test. Corneal fluorescein staining was used to observe corneal injury. Hematoxylin-eosin (HE) staining of pathological sections was performed to detect pathological changes of corneal tissue, and TUNEL staining was applied to assess corneal cell apoptosis. Molecular biological techniques were utilized to detect the levels of reactive oxygen species (ROS), malondialdehyde (MDA) and superoxide dismutase (SOD) in corneal tissue, as well as the expression of apoptosis-related proteins and inflammatory cytokines.Results　After 4 weeks of tail suspension, tear secretion volume in rats decreased. Edema was observed in the corneal epithelial and stromal layers, accompanied by disorganized collagen fibers and inflammatory cell infiltration. TUNEL staining revealed obvious apoptosis of corneal epithelial cells, and the expression trend of apoptosis-related proteins detected by Western blot in the cornea was consistent with the TUNEL staining results. The levels of ROS and MDA in rat corneal tissues were significantly higher than those in the control group (P<0.05), while the SOD level was markedly lower. Meanwhile, the expression levels of IL-1β and TNF-α in the corneal tissues of tail suspended rats were upregulated (P<0.05). Furthermore, All corneal pathological lesions were further aggravated after 8 weeks of tail suspension. Compared with the age-matched control group, the indicators including tear secretion, apoptosis-related proteins, oxidative stress markers and pro-inflammatory cytokines in the TS8W group showed extremely significant differences (P<0.01), and statistically significant differences were also observed when compared with the TS4W group (P<0.05).Conclusion Tail suspension simulating weightlessness can jointly mediate pathological damage to rat corneal tissues by inducing corneal oxidative stress imbalance and activating local inflammatory responses, and the severity of lesions increases progressively with the extension of tail suspension intervention duration. This study preliminarily elucidates the pathogenesis of corneal injury under microgravity exposure, and provides potential intervention targets and novel strategies for the prevention and treatment of microgravity-related corneal lesions.

Key words: simulated weightlessness, cornea, oxidative stress, inflammation