不同海拔高度对大鼠肾功能及生物标志物的影响

Effects of different altitudes on renal function and biomarkers in rats

目的:通过低压氧舱分别模拟海拔3500、4500及5500 m缺氧环境,探究在不同海拔高度SD大鼠肾脏的损伤程度及潜在新型肾损伤标志物的灵敏度。方法:采用低压氧舱模拟高原缺氧,设3500、4500和5500 m三个海拔高度组及平原对照组,每组各16只大鼠,均处理72 h。实验结束后取血及肾组织,测外周血象、血清肌酐(SCr)、血尿素氮和血清尿酸水平,以及肾组织中超氧化物歧化酶(SOD)、肿瘤坏死因子(TNF-α)、肝型脂肪酸结合蛋白(L-FABP)、金属蛋白酶组织抑制因子2(TIMP-2)和胰岛素样生长因子结合蛋白7(IGFBP7)水平,肾组织进行HE染色及Masson染色。结果:与对照组相比,高原缺氧组大鼠SCr水平有不同程度升高(P<0.05或P<0.01),肾组织SOD活性有不同程度降低(P<0.05或P<0.01);TNF-α、L-FABP、TIMP-2和IGFBP7含量有显著升高(P<0.01);HE染色显示随海拔高度升高,大鼠肾脏损伤逐渐加重,主要表现为肾小管上皮细胞及肾小球的变化;Masson染色显示缺氧组大鼠肾脏出现纤维化。结论:海拔3500、4500及5500 m缺氧72 h均能对大鼠肾脏造成一定损伤,其中以5500 m缺氧72 h对大鼠造成的肾脏损伤最为明显,可作为高原肾脏损伤的稳定模型;除SCr外,肾组织LFABP、TIMP-2和IGFBP7也可作为高原急性肾损伤的评价指标。

AIM:To evaluate the severity of renal injury and the sensitivity of new renal injury biomarkers in SD rats exposed to simulated altitudes of 3500,4500 and 5500 m.METHODS:Hypobaric chamber was used to simulate high-altitude hypoxia environment.The rats were divided into control group,3500 m group,4500 m group and 5000 m group(n=16 in each group).The rats in 3500 m,4500 m and 5000 m groups were treated with mimicking altitudes of 3500,4500 and 5000 m in a hypobaric chamber for 72 h.The rats in control group were treated under the same condition except hypoxia intervention.Blood and kidney were collected after the hypoxia exposure.The peripheral hemogram,the levels of serum creatinine(SCr),blood urea nitrogen and serum uric acid,and the levels of superoxide dismutase(SOD),tumor necrosis factor-α(TNF-α),liver-type fatty acid-binding protein(L-FABP),tissue inhibitor of metalloproteinase-2(TIMP-2)and insulin-like growth factor binding protein 7(IGFBP7)in the kidney were measured.The histological changes of the kidney were examined by HE and Masson staining.RESULTS:Compared with control group,the SCr in high-altitude hypoxia groups was increased(P<0.05 or P<0.01),while the activity of SOD in the kidney was decreased(P<0.05).The renal levels of TNF-α,L-FABP,TIMP-2 and IGFBP7 in high-altitude hypoxia groups were significantly higher than those in control group(P<0.01).The results of HE staining showed that renal injury was gradually aggravated with the elevation of altitude,especially in renal tubular epithelial cells and glomeruli.Renal fibrosis was observed in high-altitude hypoxia groups according to the results of Masson staining.CONCLUSION:Exposure to simulated altitudes of 3500,4500 and 5500 m for 72 h induces renal injury in rats,especially at 5500 m,which can be used as a stable model of high-altitude kidney injury.Besides SCr,renal L-FABP,TIMP-2 and IGFBP7 levels can be used as evaluation indicators of acute kidney injury at high altitude.