Renal L-type fatty acid-binding protein in acute ischemic injury
Renal L-type fatty acid-binding protein in acute ischemic injury
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DOI：
10.1681/asn.2007010097
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发表时间：
2007-11-01
影响因子：
13.6
通讯作者：
Sugaya, Takeshi
中科院分区：
文献类型：
--
作者：
Yamamoto, Tokunori;Noiri, Eisei;Sugaya, Takeshi
在组织缺氧损伤过程中，脂肪酸结合蛋白(FABP)与不饱和脂肪酸和脂质过氧化产物结合。在人类肾移植患者和动物模型中，我们评估了L型FABP(L-FABP)作为肾缺血生物标志物的潜在作用。检测12例亲属活体肾移植患者移植肾再灌注后即刻首次尿液中L-FABP水平，同时进行肾小管周围毛细血管血流活体视频分析。尿L-FABP水平与肾小管周围毛细血管血流量、移植肾缺血时间及住院时间均呈显著正相关(P均<0.0001)。在人-L-FABP转基因小鼠的缺血再灌注损伤中，免疫组织化学分析显示L-FABP从近端肾小管细胞胞浆过渡到管腔。此外，在受伤后，这些转基因小鼠表现出比受伤的野生型小鼠更低的血液尿素氮水平和更少的组织损伤，这可能是由于组织缺氧的减少。体外实验表明，与未转染细胞相比，转导h-L-FABP基因的小鼠近端肾小管上皮细胞株在低氧条件下氧化应激程度降低。综上所述，这些数据表明，脑缺血再灌注损伤后尿L-FABP升高可能成为急性脑缺血损伤的一种生物标志物。
Fatty acid-binding proteins (FABPs) bind unsaturated fatty acids and lipid peroxidation products during tissue injury from hypoxia. We evaluated the potential role of L-type FABP (L-FABP) as a biomarker of renal ischemia in both human kidney transplant patients and animal models. Urinary L-FABP levels were measured in the first urine produced from 12 living-related kidney transplant patients immediately after reperfusion of their transplanted organs, and intravital video analysis of peritubular capillary blood flow was performed simultaneously. A significant direct correlation was found between urinary L-FABP level and both peritubular capillary blood flow and the ischemic time of the transplanted kidney (both P < 0.0001), as well as hospital stay (P < 0.05). In human-L-FABP transgenic mice subjected to ischemia-reperfusion injury, immunohistological analyses demonstrated the transition of L-FABP from the cytoplasm of proximal tubular cells to the tubular lumen. In addition, after injury, these transgenic mice demonstrated lower blood urea nitrogen levels and less histological injury than injured wild-type mice, likely due to a reduction of tissue hypoxia. In vitro experiments using a stable cell line of mouse proximal tubule cells transfected with h-L-FABP cDNA showed reduction of oxidative stress during hypoxia compared to untransfected cells. Taken together, these data show that increased urinary L-FABP after ischemic-reperfusion injury may find future use as a biomarker of acute ischemic injury.