肾损伤分子-1在急性缺血缺氧再灌注大鼠肾组织中的表达及意义

The expression and signification of kidney injury molecule-1 on renal ischemia reperfusion injury in rat

目的 观察肾损伤分子-1（kidney injury molecule-1，KIM-1）在急性缺血缺氧再灌注肾损伤（acute ischemia reperfusion kidney injury，AIKI）大鼠肾组织中的表达及分布规律，探讨其在诊断急性肾损伤（acute kidney injury，AKI）中的价值。方法 采用清洁级SD大鼠128只，随机分为对照组和模型组，模型组按国际标准建立大鼠AIKI模型，分别于2 h、6 h、24 h、48 h、72 h、1周、2周、4周处死（n＝8），取肾组织，常规HE染色，参照Sayhan等标准对肾小管间质损伤进行半定量评分；免疫组织化学、Western blot法检测KIM-1蛋白的表达及分布；生化法测定血清肌酐（serum creatinine，Scr）水平。结果 （1）大鼠缺血再灌注后2 h即出现明显肾小管间质损伤，随着再灌注时间延长损伤加重，48 h达高峰后逐渐减轻，但仍高于对照组（P〈0.01）；（2）Western blot和免疫组织化学检测发现，缺血再灌注后2 h肾组织KIM-1的表达明显升高，KIM-1表达水平与肾小管间质损伤评分呈显著正相关（r＝0.887，P＝0.003）；（3）大鼠缺血再灌注后2 h Scr明显升高，48 h达到最高值后降至正常，其升高与肾小管间质损伤评分无相关性（r＝0.280，P＝0.502）。结论 AIKI模型中大鼠肾组织KIM-1蛋白表达水平显著增加，其表达水平与肾小管间质损伤评分呈正相关，与Scr相比，KIM-1可能为更准确地反映肾损伤情况的指标。

Objective To observe the expression levels of kidney injury molecule-1（KIM-1） in renal tissues of ischemia-reperfusion rats, and to explore the value in the diagnosis of acute kidney injury. Methods Rats were randomly divided into two groups, control（CON） group （n=64） and acute kidney ischemia reperfusion injury （AIKI） group （n=64）. Rats were sacrificed following reperfusion 2 h, 6 h, 24 h, 48 h, 72 h, 1 week （w）, 2 w, and 4 w. The changes of morphology were checked on HE staining sections under light microscope.The extent of tubulointerstitial injury was determined by Sayhan classification.The distribution and expression of KIM-1 in renal tissue were observed by immunohistochemistry and Western blotting.Serum samples were collected and serum creatinine measurement was performed at different reperfusion time points. Results （1） Compared with the CON group, the renal tubulointerstitial injury scores of AIKI group were significantly higher at all times after reperfusion （P〈0.01）. （2） The expression of KIM-1 was consistent with the tubulointerstitial injury.The positive correlation between KIM-1 and the tubulointerstitial injury scores was significant（r=0.887, P=0.003）. （3） Compared with the CON group, serum creatinine in AIKI group was significant higher at 2 h, 6 h, 24 h, 48 h, 72 h after reperfusion （P〈0.05）. Serum creatinine had no correlation with the damage of renal tubulointerstitial. Conclusion The expression of KIM-1 increases significantly in renal ischemia reperfusion injury, and it is consistent with the tubulointerstitial injury.Compared with serum creatinine, KIM-1 may be a more accurate biomarker of renal damage.