Sprague-Dawley大鼠肾脏急性缺血再灌注损伤的代谢组学研究

Metabolomics analysis of renal acute ischemia/reperfusion injury in Sprague-Dawley rats

目的系统分析急性肾损伤动物模型体内代谢产物,以评估代谢组学能否早期发现急性肾损伤,进一步寻找新的诊断生物标记物及治疗方法。方法建立肾脏急性缺血再灌注损伤动物模型,收集不同时间点的动物血清,利用高分辨率液相色谱/四级杆-飞行时间-质谱串联的方法对动物血清标本进行代谢产物的分析。结果术后4 h手术组大鼠的血清肌酐、尿素氮显著高于假手术组(P值均<0.01)。代谢组学能在2～72 h各时间点区分手术组与假手术组。差异代谢产物主要有卡尼汀及其衍生物和磷脂酰胆碱分解代谢产物两类,卡尼汀及短链脂酰卡尼汀在缺血再灌注损伤模型血清中含量降低,而后一类物质的血清浓度则有不同程度的升高。结论代谢组学能够早于血清肌酐、尿素氮的变化而发现肾脏损伤,可用于急性肾损伤的早期诊断。

Objective To systematically analyze the metabolites in animal model of acute kidney injury （AKI） and to evaluate whether metabolomic technology can detect AKI at an early stage, so as to further search for new biomarkers and therapy target of AKI. Methods The acute kidney injury model of IRI （ischemia/reperfusion injury） was established in Sprague-Dawley rats. The blood samples were taken at different time points and the metabolites in the samples were subjected to high resolution liquid chromatography/quadrupole-time of flight-mass spectrometer （HPLC-MS）-based metabonamic analysis. Results Serum creatinine and blood urea nitrogen in the operation group were significantly higher than those of the sham operation group （both P〈0.01 ）. Metabolomics measurements could differentiate the reperfusion injury between the operation group and the sham operation group within 2- 72 h after operation. The metabolite profile could detect the renal injury earlier than the changes of serum creatinine and urea nitrogen. The differential metabolites mainly included carnitines and phosphatidylcholines. The carnitines were down- regulated and the phosphatidylchelines were up-regulated in the IRI model. Conclusion The metabolite profile can detect AKI earlier than the changes of serum creatinine and blood urea nitrogen. （Shanghai Med J, 2009, 32..184-187）