Melin Jan, Hellberg Olof, Funa Keiko, Hällgren Roger, Larsson Erik, Fellström Bengt C
Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Nephron Exp Nephrol. 2006;103(3):e86-94. doi: 10.1159/000092193. Epub 2006 Mar 22.
BACKGROUND/AIMS: Unilateral renal ischemia during 30 min causes severe, non-reversible renal damage in diabetic (DM) rats, but not in nondiabetic rats. Hyaluronan (HA) is a glycosaminglycan involved in various forms of renal injury. We examined the role of HA and CD44, a major receptor for HA, in the development of postischemic renal injury in DM rats.
The left renal artery of streptozotocin diabetic Wistar rats was clamped for 30 min. The HA content in the kidneys was measured. A biotinylated HA-binding probe was used to localize HA. Inflammatory cells and other cells expressing CD44 were identified by immunohistochemistry.
In ischemic DM kidneys the renal HA-content started to increase already after 24 h and significantly so after 1-8 weeks after ischemia/reperfusion (I/R). The relative water content of the kidneys increased in parallel. HA started to appear in the cortex of ischemic DM kidneys 1 week after I/R. In contrast, the non-DM ischemic kidneys showed no increase of HA and water content after 1-8 weeks after I/R. The tubular cells in the cortex and outer medulla demonstrated increased staining for CD44. In the same compartments the increased numbers of infiltrating inflammatory cells also expressed CD44.
HA-accumulation in the renal cortex might contribute to the renal damage seen after transient ischemia in DM rats by promoting inflammation through interaction between HA and CD44 expressing inflammatory cells. Furthermore, HA accumulation may contribute to an interstitial renal edema.
背景/目的：30分钟的单侧肾缺血会导致糖尿病（DM）大鼠出现严重的、不可逆的肾损伤，但不会导致非糖尿病大鼠出现这种情况。透明质酸（HA）是一种参与多种形式肾损伤的糖胺聚糖。我们研究了HA及其主要受体CD44在糖尿病大鼠缺血后肾损伤发展中的作用。
将链脲佐菌素诱导的糖尿病Wistar大鼠的左肾动脉夹闭30分钟。测量肾脏中的HA含量。使用生物素化的HA结合探针定位HA。通过免疫组织化学鉴定表达CD44的炎症细胞和其他细胞。
在缺血的糖尿病肾脏中，肾HA含量在缺血/再灌注（I/R）后24小时就开始增加，在1-8周后显著增加。肾脏的相对含水量也随之平行增加。I/R后1周，HA开始出现在缺血糖尿病肾脏的皮质中。相比之下，非糖尿病缺血肾脏在I/R后1-8周HA和含水量没有增加。皮质和外髓质的肾小管细胞CD44染色增加。在相同区域，浸润性炎症细胞数量增加，这些细胞也表达CD44。
肾皮质中HA的积累可能通过HA与表达CD44的炎症细胞之间的相互作用促进炎症反应，从而导致糖尿病大鼠短暂缺血后出现肾损伤。此外，HA的积累可能导致肾间质水肿。
