Göransson Viktoria, Johnsson Cecilia, Jacobson Annica, Heldin Paraskevi, Hällgren Roger, Hansell Peter
Division of Integrative Physiology, Department of Medical Cell Biology, Uppsala University, BMC, PO Box 571, SE-751 23 Uppsala, Sweden.
Nephrol Dial Transplant. 2004 Apr;19(4):823-30. doi: 10.1093/ndt/gfh003.
Hyaluronan (HA) is a connective tissue component with unique water binding and pro-inflammatory properties. It has been suggested that HA is involved in normal renal water handling but also in several pathological conditions such as organ rejection and ischaemia-reperfusion (IR) injury.
In anaesthetized normal rats we investigated if renal cortical HA accumulation and the intrarenal distribution and expression of HA synthases (Has 1, 2 and 3) correlate with renal dysfunction after renal IR injury. After 20, 30 or 45 min of unilateral renal ischaemia and 72 h of reperfusion, renal function and cortical HA content were measured. Has 1, 2 and 3 mRNA were determined in control and IR kidneys subjected to 45 min ischaemia and 72 h reperfusion.
IR kidneys had reduced urine concentrating ability, potassium excretion, glomerular filtration rate (GFR) and renal blood flow. On average, IR kidneys had more than 10 times higher amounts of cortical HA than the contralateral control kidney and their water content was elevated while medullary HA was largely unaffected. Has 2 expression in the cortex was heavily up-regulated in IR kidneys while Has 3 remained at control levels. Has 1 could never be detected. There was a direct correlation between the amount of cortical HA and the time period of ischaemia and also between the cortical amount of HA and depression of functional parameters.
IR injury depresses parameters of renal function, which coincides with an elevated cortical HA content and Has 2 expression. The enhanced Has 2 expression indicates that the cortical HA accumulation is primarily dependent on increased HA synthesis and not impaired degradation/elimination. The water binding and pro-inflammatory properties of HA may contribute to renal dysfunction after IR.
透明质酸（HA）是一种结缔组织成分，具有独特的水结合和促炎特性。有人提出，HA不仅参与正常的肾脏水代谢，还与多种病理状况有关，如器官排斥和缺血再灌注（IR）损伤。
在麻醉的正常大鼠中，我们研究了肾脏IR损伤后肾皮质HA积累、HA合成酶（Has 1、2和3）的肾内分布及表达是否与肾功能障碍相关。在单侧肾脏缺血20、30或45分钟并再灌注72小时后，测量肾功能和皮质HA含量。测定对照肾脏和经历45分钟缺血及72小时再灌注的IR肾脏中的Has 1、2和3 mRNA。
IR损伤的肾脏尿浓缩能力、钾排泄、肾小球滤过率（GFR）和肾血流量降低。平均而言，IR损伤的肾脏皮质HA含量比对侧对照肾脏高出10倍以上，其含水量升高，而髓质HA基本未受影响。IR损伤的肾脏中皮质Has 2表达显著上调，而Has 3保持在对照水平。从未检测到Has 1。皮质HA量与缺血时间以及皮质HA量与功能参数降低之间存在直接相关性。
IR损伤会降低肾功能参数，这与皮质HA含量升高和Has 2表达增加相吻合。Has 2表达增强表明皮质HA积累主要依赖于HA合成增加，而非降解/清除受损。HA的水结合和促炎特性可能导致IR损伤后的肾功能障碍。
