Role of Renal Heme Oxygenase-1 in Response to Ischemia/Reperfusion in Rats Preconditioned By Hypoxia and/or Remote Ischemia

低氧預處理和／或遠端缺血預處理中第一型血基質氧化酶對於缺血再灌流腎臟之保護角色

趙玉雯(Yu-Wen Chao) ； 楊芝青(Jing-Ying Huang) ； 黃菁英(Chih-Ching Yang) ； 張朝富(Chau-Fu Chang) ； 陳達隆(Dar-Long Cheng) ； 范俊雄(Jung-Siong Fan) ； 鄭劍廷(Chiang-Ting Chien) ； 陳朝峰(Chau-Fong Chen)

《Acta Nephrologica》 24卷2期 (2010/06) Pp. 101-108

摘要

背景：血基質氧化酶(heme oxygenase, HO)，為血基質代謝分解過程中之速率決定步驟酵素，其中第一型血基質氧化釀(HO-1)為誘發表現型。HO-1可受到缺氧的刺激而產生，並可以對具傷害性之刺激產生適應性，降低組織的傷害，包括了腎臟缺血再灌流(renal ischemia reperfusion, I/R)之傷害。因此在本研究探討遠端缺血預處理和／或低氧預處理，對腎臟缺血再灌流傷害的影響，以及HO-1在其中所扮演的角色。
方法：本實驗將所使用的雌性Wistar大鼠分成四組：分別為海平面組（sea level, SL; 101.3千帕）；遠端缺血預處理組(remote ischemic preconditioning, SLR)：低氧預處理組（hypoxia adapted, HA; 50.7千帕之低氧艙四週）；低氧預處理後進行遠端缺血預處理組(HAR)。各組動物再隨機分為對照亞組及接受腎臟缺血再灌流（I/R：將腎動脈夾閉四十五分鐘隨後再灌流四小時）亞組。
結果：以西方墨點法觀察HO-1的蛋白質表現與酵素活性測定，在SLR、HA和HAR組都明顯的較SL組增加。在腎功能測定方面，則給予HO抑制劑－鋅前吡喀紫質(zinc-protoporphyrin IX, ZnPP IX)後，觀察腎小球過濾率(glomerular filtration rate, GFR)和腎血流量的變化。本實驗在接受腎臟缺血再灌流亞組中，SLR、HA和HAR組在腎小球過濾率和腎血流的表現皆優於SL組。
結論：低氧預處理和／或遠端缺血預處理可誘發大鼠腎臟內HO-1的增加，對於腎臟缺血再灌流所造成的傷害具有緩和的效果。

關鍵字

血基質氧化酶 ； 缺血預處理 ； 低氧預處理 ； 缺血再灌流 ； 遠距缺血預處理

並列摘要

Background: Heme oxygenase (HO) is the rate-limiting enzyme for heme degradation, curd HO-1 is the inducible isoform. Induction of HO-1 is an adaptive response to injurious stimuli such as renal ischemia reperfusion (I/R). We examined the effect of preconditioning on response to renal I/R injury and the role of HO-1 in this response.
Methods: Female Wistar rats were divided into four groups: sea level (SL, I atm=101.3 kPa): hvpoxic preconditioning (HA, 4 wks at 50.7 kPu); remote surgical ischemic preconditioning (SLR); and preconditioning by hypoxia and remote surgical ischemia (HAR). Each group was randomized into control curd renal I/R subgroups.
Results: HO-1 protein expression and enzymatic activity was singificantly higher in the HA, SLR, and HAR groups than in the SL group. ZnPP IX (HO inhibitor) was administered to assess changes in renal function, as determined by glomerular filtration rate (GFR) and renal blood/low. The renal function of undergoing I/R in the SLR, HA, and HAR groups were better than that of rats in the SL group.
Conclusion: Renal preconditioning by hypoxia or a remote surgical procedure increased renal HO-1 expression and enzymatic activity. This appears to have a protective effect on the kidney in response to renal I/R injury.

並列關鍵字

Heme oxygenase ； hypoxic preconditioning ； ischemic preconditioning ； ischemic reperfusion ； remote ischemic preconditioning