【摘要】 目的分析在不同缺氧状态下大鼠肾组织中缺氧诱导因子-1αmRNA(HIF-1αmRNA)水平表达和血清超氧化物歧化酶(SOD)及丙二醛(MDA)含量变化,探讨阻塞性睡眠呼吸暂停低通气综合征(OSAHS)肾损伤的特点。方法 30只大鼠,采用随机数字表法分为正常对照组、间歇性缺氧组和持续性缺氧组,每组10只。正常对照组大鼠不予任何处理,剩余两组分别放入间歇性缺氧/再氧合动物舱建立慢性间歇性缺氧(CIH)和持续性缺氧大鼠模型。造模15 d后,收集三组大鼠24 h尿液,检测尿蛋白定量,酶联免疫吸附试验(ELISA)方法检测各组血清SOD及MDA水平,苏木精—伊红染色法(HE)染色观察肾组织形态学改变做肾小管损伤评分,实时荧光定量聚合酶链反应(PCR)检测肾组织HIF-lαmRNA的表达量。比较三组一般情况、血清SOD、MDA、24 h尿蛋白定量、肾小管损伤程度评分、HIF-1αmRNA水平,分析HIF-1αmRNA和血清MDA与24 h尿蛋白定量、肾小管损伤程度的相关性。结果正常对照组大鼠反应敏捷,毛发光亮,精神状况良好。持续性缺氧组和间歇性缺氧组大鼠行动迟缓,毛发稀疏,消瘦。正常对照组体重(210.03±15.71)g明显高于间歇性缺氧组的(185.94±6.79)g和持续性缺氧组的(169.18±10.23)g,间歇性缺氧组体重高于持续性缺氧组,差异均有统计学意义(P<0.05)。正常对照组血清SOD水平明显高于间歇性缺氧组和持续性缺氧组, 24 h尿蛋白定量、血清MDA、肾小管损伤程度评分均明显低于间歇性缺氧组和持续性缺氧组,差异均有统计学意义(P<0.05)。间歇性缺氧组血清MDA、肾小管损伤程度评分均明显高于持续性缺氧组,血清SOD水平明显低于持续性缺氧组,差异均有统计学意义(P<0.05)。间歇性缺氧组和持续性缺氧组24 h尿蛋白定量比较差异无统计学意义(P>0.05)。正常对照组HIF-1αmRNA水平(0.23±0.18)明显低于间歇性缺氧组的(0.78±0.33)、持续性缺氧组的(0.52±0.13),而间歇性缺氧组HIF-1αmRNA水平高于持续性缺氧组,差异均有统计学意义(P<0.05)。HIF-1αm RNA与24 h尿蛋白定量、肾小管损伤程度呈正相关(r=0.65、0.78, P<0.05);血清MDA与24 h尿蛋白定量、肾小管损伤程度呈正相关(r=0.68、0.72, P<0.05)。结论慢性缺氧抑制大鼠生长发育,出现肾功能损伤, CIH以肾小管的损伤更加明显, CIH与持续性缺氧相比较高水平的HIF-1αmRNA表达提示机体处于缺氧应激状态, CIH肾损害可能与氧化应激状态及高水平的HIF-1αmRNA表达有关。更多还原

【Abstract】 Objective To analyze the expression of hypoxia-inducible factor-1 α mRNA(HIF-1 α mRNA) and the changes of superoxide dismutase(SOD) and malondialdehyde(MDA) in rats under different hypoxia conditions, and to discuss the characteristics of renal injury in obstructive sleep apnea hypopnea syndrome(OSAHS). Methods A total of 30 rats were randomly divided into normal control group, intermittent hypoxia group and persistent hypoxia group according to random numerical table, with 10 rats in each group. The rats in the normal control group were not treated, and the remaining two groups were put into intermittent hypoxia/reoxygenation animal cabins to establish chronic intermittent hypoxia(CIH) and persistent hypoxia rat models. After 15 d of modeling, the 24 h urine of the three groups of rats was collected, and the urine protein was measured. The enzyme-linked immunosorbent assay(ELISA) method was used to detect the serum SOD and MDA levels in each group. Hematoxylin-Eosin(HE) staining was used to observe the morphological changes of renal tissues to score renal tubular damage, and real-time fluorescent quantitative polymerase chain reaction(PCR) to detect the expression of HIF-1α mRNA in renal tissues. The general condition, serum SOD, MDA, 24-h urinary protein quantification, renal tubular injury score, HIF-1 α mRNA level were compared among the three groups, and the correlation between HIF-1 α mRNA, serum MDA and 24-h urinary protein quantification, renal tubular injury degree was analyzed. Results The rats in the normal control group had quick response, bright hair and good mental condition. The rats in the persistent hypoxia group and the intermittent hypoxia group were slow, with sparse hair and weight loss. The weight(210.03±15.71) g of normal control group was obviously higher than(185.94±6.79) g of persistent hypoxia group and(169.18±10.23) g of intermittent hypoxia group, and intermittent hypoxia group was higher than persistent hypoxia group, and the difference was statistically significant(P<0.05). The serum SOD of normal control group was obviously higher than intermittent hypoxia group and persistent hypoxia group, and 24-h urinary protein quantification, renal tubular injury score were obviously lower than intermittent hypoxia group and persistent hypoxia group, and the difference was statistically significant(P<0.05). The serum MDA and renal tubular injury score of intermittent hypoxia group were obviously higher than persistent hypoxia group, and serum SOD was obviously lower than persistent hypoxia group, and the difference was statistically significant(P<0.05). There was no statistically significant difference in 24-h urinary protein quantification between intermittent hypoxia group and persistent hypoxia group(P>0.05). HIF-1αmRNA(0.23±0.18) of normal control group was obviously lower than(0.78±0.33) of intermittent hypoxia group and(0.52±0.13) of persistent hypoxia group, and HIF-1αmRNA of intermittent hypoxia group was higher than persistent hypoxia group, and the difference was statistically significant(P<0.05). HIF-1α mRNA was positively correlated with 24-h urinary protein quantification and renal tubular injury(r=0.65, 0.78, P<0.05). Serum MDA was positively correlated with 24-h urinary protein quantification and renal tubular injury(r=0.68, 0.72, P<0.05). Conclusion Chronic hypoxia inhibits the growth and development of rats, resulting in renal function injury. The injury of renal tubules in CIH was more obvious. Compared with persistent hypoxia, the higher level of HIF-1αmRNA expression in CIH suggests that the body is in a state of hypoxic stress. CIH renal damage may be related to oxidative stress and high levels of HIF-1αmRNA expression.更多还原