Objective: To investigate the effects of intermittent hypoxia (IH) exposure on renal tubular epithelial cell injury and autophagy in rats. Methods: A total of 12 Sprague Dawley (SD) rats were randomly divided into two groups: normal control (NC) group and IH group, with 6 rats in each group. An IH animal model was established to observe the effects of IH on renal tubular epithelial cell damage and autophagy in rats. Microalbumin (mAlb) was detected by immunoturbidimetry. Neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1(KIM-1)in urine were assessed by enzyme-linked immunosorbent assay (ELISA) test. The pathological damage of renal tubules was observed by hematoxylin-eosin (HE) staining. The expression of autophagy marker protein light chain 3 (LC3) and Beclin-1 were detected by immunohistochemistry and immunoblotting. Results: At the end of the test, the levels of mAlb [(34.7±6.7) mg/L vs (11.1±3.3) mg/L, P=0.011], NGAL [(17.3±3.9) ng/ml vs(4.0±1.7)ng/ml, P=0.011] and KIM-1 [ (10.8±2.7) ng/ml vs (2.6±1.0) ng/ml, P=0.016] in urine of IH group were higher than those of control group, and the differences were statistically significant (all P<0.05). Pathological injury was showed by HE staining in IH group. The increase of autophagy in IH group was more obvious than that in NC group. Besides, the expression level of autophagy markers (protein LC3 and Beclin-1) was significantly higher in IH group than that in NC group (P<0.05). Conclusions: IH can not only cause renal tubular injury, but also induce increased autophagy in renal tubular epithelial cells. Autophagy activation might participate in renal tubular epithelial cell injury induced by IH.
目的： 探讨间歇低氧暴露对大鼠肾小管上皮细胞损伤及自噬的影响。 方法： 选取12只成年雄性SD大鼠，随机分为正常对照组和间歇低氧组，每组6只，建立间歇低氧动物模型，观察其对大鼠肾小管上皮细胞损伤及自噬的影响。免疫比浊法检测尿微量白蛋白，酶联免疫吸附试验(ELISA)检测两组大鼠尿中性粒细胞明胶酶相关脂质运载蛋白(NGAL)及尿肾损伤因子1(KIM－1)水平，苏木精－伊红(HE)染色观察肾小管病理损伤，免疫组化及Western印迹检测两组大鼠肾小管上皮细胞自噬标记蛋白LC3和Beclin－1的表达。 结果： 实验第6周时，间歇低氧组大鼠尿微量白蛋白[(34.7±6.7)mg/L比(11.1±3.3)mg/L，P＝0.011]、尿NGAL[(17.3±3.9)ng/ml比(4.0±1.7)ng/ml, P＝0.011]及KIM－1[ (10.8±2.7)ng/ml比(2.6±1.0)ng/ml, P＝0.016]较对照组水平升高，差异均有统计学意义(均P<0.05)；HE染色法显示间歇低氧组大鼠肾小管上皮细胞出现病理损伤；免疫组化和Western印迹结果显示间歇低氧组大鼠肾小管上皮细胞比对照组自噬标记蛋白表达明显增多。 结论： 间歇低氧暴露可导致肾小管上皮细胞损伤，同时伴有肾小管上皮细胞自噬标记蛋白表达增多，提示自噬增多可能参与了间歇低氧诱导的肾小管上皮细胞损伤。.
Keywords: Anoxia; Autophagy; Renal tubular epithelial cells; Sleep apnea, obstructive.