| 高丽梅,张紫怡,覃志成.Klotho在大鼠缺血性急性肾损伤中的动态变化意义研究[J].安徽医药,2025,29(7):1406-1410. |
| Klotho在大鼠缺血性急性肾损伤中的动态变化意义研究 |
| Implications of dynamic changes of Klotho in rats with ischemic acute kidney injury |
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| DOI：10.3969/j.issn.1009-6469.2025.07.028 |
| 中文关键词: 克老素基因 缺血再灌注 急性肾损伤 动态变化 生物学标志物 |
| 英文关键词: Klotho gene,KL gene Ischemia-reperfusion Acute renal injury Dynamic change Biological marker |
| 基金项目:山西省卫生健康委员会科研课题项目( 2022004) |
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| 中文摘要: |
| 目的观察 Klotho蛋白在急性肾损伤( acute kidney injury，AKI)中的动态变化及意义。方法 2022年 1月至 2023年 10月将 30只健康雄性 SD大鼠采用随机数字表法分为假手术组( Sham组)、缺血再灌注( ischemia/reperfusion，I/R)6h、12 h、 24 h、48 h组，每组 6只， I/R组大鼠摘除右肾后，用无创动脉夹夹闭左肾蒂， 45 min后解除，建立 I/R AKI模型， Sham组不给予夹闭，余步骤同前，各组于造模成功后分批处死，收集相应的血和肾组织标本。比色法分别检测血清尿素氮、血肌酐、肾组织丙二醛和超氧化物歧化酶( SOD)水平， HE染色观察肾组织病理改变，蛋白质印迹法检测肾组织 Klotho蛋白表达，免疫组化观察 Klotho肾组织表达情况。结果与 Sham组相比， I/R组大鼠分别于 6h、12 h血清尿素氮、血肌酐浓度及肾组织丙二醛含量开始升高［( 5.13±0.35)mmol/L比( 7.39±0.38)mmol/L比( 10.24±0.54)mmol/L；(49.39±4.34)μmol/L比( 82.77±5.85)μmol/ L比( 120.89±3.40)μmol/L；(2.79±0.27)nmol/mg比( 4.37±0.34)nmol/mg比( 5.57±0.27)nmol/mg，均 P<0.01］于 24 h达顶峰，肾小管上皮细胞明显变性、坏死， 48 h较 24 h下降但仍高于 Sham组( P<0.05)；而肾组织 SOD活性及 Klotho表，达随缺血再灌注时间延长呈阶梯性下降(均 P<0.05)于 24 h达到最低值，至 48 h未恢复正常。结论随着肾损伤的加重， Klotho蛋白在大鼠缺血再灌注 AKI中表达显著下调，于2，4 h降至最低，在 AKI病理生理机制中具有重要意义。 |
| 英文摘要: |
| Objective To observe the dynamic changes and implications of Klotho protein in acute kidney injury (AKI) induced by ischemia-reperfusion.Methods This study was conducted from January 2022 to October 2023. Thirty healthy male SD rats were ran-domly assigned, using a random number table method, into the following groups: Sham operation group (Sham group), ischemia-reperfu-sion (I/R) 6 h, 12 h, 24 h and 48 h groups, with 6 rats in each group. After the right kidney was removed in I/R groups, the left renalpedicle was clipped with non-invasive artery clamp for 45 min and subsequently released to establish an ischemia-reperfusion AKImodel. The rats of Sham group were not clipped, and the remaining steps were the same as those of I/R groups. After successful estab-lishment of the models, the rats in each group were killed in batches, and the corresponding blood and renal tissue samples were taken.The levels of blood urea nitrogen (BUN), serum creatinine (Scr), malondialdehyde (MDA) and superoxide dismutase (SOD) in renal tis-sue were measured by colorimetry. HE staining was used to observe the pathological changes of renal tissue. The expression of Klothoprotein in renal tissue was detected by Western blotting, and its expression was observed by immunohistochemistry. Results Com-pared with the Sham group, the I/R group showed that the concentrations of BUN and Scr in serum, as well as MDA in renal tissue, be-gan to increase at 6 h and 12 h respectively [(5.13±0.35) mmol/L vs. (7.39±0.38) mmol/L vs. (10.24±0.54) mmol/L;(49.39±4.34) μmol/L vs. (82.77±5.85) μmol/L vs. (120.89±3.40) μmol/L;(2.79±0.27) nmol/mg vs. (4.37±0.34) nmol/mg vs. (5.57±0.27) nmol/mg, all P<0.01],and reached the peak at 24 h. Renal tubular epithelial cells were observed to be obviously degenerated and necrotic. These indexes de-creased at 48 h compared with those at 24 h, but were still higher than the indexes in Sham group (P<0.05). However, SOD activity and Klotho expression in renal tissue decreased step by step with the prolongation of ischemia-reperfusion time (both P<0.05), reaching the lowest value at 24 h and not returning to normal at 48 h.Conclusion With the aggravation of renal injury, the expression of Klotho pro-tein is significantly down-regulated in rats with ischemia-reperfusion AKI, and reaches its lowest level at 24 h, which is of critical im- |
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