广西医学

目的探讨不同海拔高度对大鼠肠道屏障功能的影响，分析血液及尿液中肠型脂肪酸结合蛋白（I⁃FABP）水平与肠道屏障功能损伤的相关性。方法将18只健康雄性SD大鼠随机分为对照组、3 500 m高原组和5 000 m高原组，每组6只。构建大鼠急性高原肠道屏障功能损伤模型，通过光学及电子显微镜观察3组大鼠空肠绒毛结构变化情况，检测并比较3组大鼠空肠绒毛高度和空肠隐窝深度；采用Western blot检测并比较3组大鼠空肠组织中Claudin⁃1、闭合蛋白（Occludin）及闭锁小带蛋白1（ZO⁃1）表达水平；采用ELISA检测并比较3组大鼠血清中肠道屏障通透性指标［二胺氧化酶（DAO）、D⁃乳酸（D⁃LA）、磷酸脂多糖（LPS）］和血清及尿液中的I⁃FABP水平。采用Pearson相关性分析血清及尿液中I⁃FABP水平与肠道屏障功能损伤相关指标的相关性。结果光学和扫描电子显微镜下显示，3 500 m高原组和5 000 m高原组大鼠空肠绒毛结构损伤，绒毛高度缩短，隐窝变浅。3 500 m高原组和5 000 m高原组大鼠的空肠绒毛高度、空肠隐窝深度及空肠组织中Claudin⁃1、Occludin、ZO⁃1表达水平较对照组大鼠减小或降低，且5 000 m高原组大鼠的上述指标较3 500 m高原组大鼠减小或下降（P<0.05）。3 500 m高原组和5 000 m高原组大鼠的血清DAO、D⁃LA、LPS、I⁃FABP水平和尿液I⁃FABP水平高于对照组大鼠，且5 000 m高原组大鼠上述指标高于3 500 m高原组大鼠（P<0.05）。相关性分析结果显示，血清I⁃FABP水平与血清DAO、LPS水平呈正相关（P<0.05），尿液I⁃FABP水平与血清I⁃FABP、DAO、LPS、D⁃LA水平呈正相关（P<0.05），血清和尿液I⁃FABP水平与空肠组织中Claudin⁃1、Occludin、ZO⁃1表达水平呈负相关（P<0.05）。结论急性高原环境可导致大鼠肠道屏障功能损伤，表现为空肠绒毛病理结构受损、紧密连接蛋白表达水平下降及通透性增加，血清和尿液中I⁃FABP水平与肠道屏障功能损伤呈正相关，提示I⁃FABP是反映肠道黏膜损伤的重要生物标志物。

Objective To investigate the effects of different altitudes on intestinal barrier function in rats, and to analyze the correlation between intestinal fatty acid binding protein (I⁃FABP) levels in blood and urine and intestinal barrier dysfunction. Methods Eighteen healthy male SD rats were randomly divided into control group, 3500 m plateau group, or 5000 m plateau group, with 6 rats in each group. A rat model of acute high⁃altitude intestinal barrier dysfunction was established. The structural changes of jejunal villi in the three groups were observed using light and electron microscopy. The jejunal villus height and crypt depth were measured and compared between rats in the three groups. Western blot was used to detect and compare the expressions of Claudin⁃1, Occludin, and zonula occludens 1 (ZO⁃1) in jejunal tissue. ELISA was used to measure and compare serum levels of intestinal permeability markers including diamine oxidase (DAO), D⁃lactate acid (D⁃LA), lipopolysaccharide (LPS) and I⁃FABP levels in serum and urine. Pearson correlation analysis was performed to assess the correlation between serum/urine I⁃FABP levels and intestinal barrier dysfunction⁃associated indices. Results Light and scanning electron microscopy revealed that structural damage to jejunal villi in rats from both the 3500 m and 5000 m plateau groups, characterized by shortened villus height and shallower crypts. Compared to the control group, the 3500 m and 5000 m plateau groups showed decreased jejunal villus height, crypt depth, and expressions of Claudin⁃1, Occludin, and ZO⁃1 in jejunal tissue; in addition, these decreases were more pronounced in the 5000 m plateau group compared to the 3500 m plateau group (P<0.05). Serum levels of DAO, D⁃LA, LPS, I⁃FABP, and urine I⁃FABP level were higher in both 3500 m and 5000 m plateau groups compared to the control group, with the 5000 m plateau group showing higher levels than the 3500 m plateau group (P<0.05). Correlation analysis indicated that serum I⁃FABP level positively correlated with serum DAO and LPS levels (P<0.05). Urine I⁃FABP level positively correlated with serum I⁃FABP, DAO, LPS, and D⁃LA levels (P<0.05). Both serum and urine I⁃FABP level negatively correlated with the expressions of Claudin⁃1, Occludin, and ZO⁃1 in jejunal tissue (P<0.05). Conclusion Acute high⁃altitude exposure can lead to intestinal barrier dysfunction in rats, manifested as pathological damage to jejunal villi structure, decreased expression of tight junction proteins, and increased permeability. Serum and urine I⁃FABP levels positively correlates with intestinal barrier dysfunction, suggesting that I⁃FABP is an important biomarker reflecting intestinal mucosal injury.