| Summary: | 碩士 === 國立臺灣大學 === 生理學研究所 === 92 === Abstract
Heme oxygenase (HO), is the rate-limiting enzyme for heme degradation. There are three isoforms of HO: an inducible form, HO-1, and two constitutive isoforms HO-2 and HO-3. The HO-1 isoform is induced by a variety of stimuli, including hypoxia, hyperoxia, oxidative stress etc. Induction of HO-1 occurs as an adaptive and beneficial response to injurious stimuli, including acute renal injury such as renal ischemia reperfusion (I/R).
The protective mechanism of HO-1 has been implicated in the removal of potentially toxic heme molecules and a lipid- soluble iron from intracellular space, in generation of antioxidant bile pigments and vasodilative carbon monoxide (CO). Metalloporphyrins which inhibit HO decrease renal medullary blood flow in normal rats and total blood flow in hypoxic adapted (HA) rats. Vascular HO-1 expression is enhanced by HA and HA elicits reduced systemic responsiveness to vasoconstrictors. The vasodilatory effect on renal blood flow of HA rats may be influenced by the formation and actions of HO-1 derived CO.
Ischemic precondition (IP) describes the phenomenon wherein pretreatment with brief ischemia and a short period of reperfusion showed a beneficial effect on the damage caused by prolonged ischemia. Remote ischemic preconditioning means “precondition at a distance” derived from the idea of protection of the myocardium by making a remote organ such as small intestine. It suggests that substances are stored in peripheral organs that when given the proper stimulus are released and exert their activity on the target organ. Though stress in remote organs has been shown to produce a protective effect in target organ, the mediators that facilitate this response are under studies. In the present study we test the hypothesis that short periods of limb ischemia induced remote precondition could reduce renal I/R injury that is mediated via the induction of HO-1.
The present study investigated the role of HO-1 in the renal function of renal I/R. Female Wistar rats were divided into four groups: sea level (SL); hypoxic preconditioning (HA, 4wk at 380 Torr, 5500 m); remote ischemic preconditioning (SLR) by 4 cycles of 10 min femoral artery occlusion and 10 min reperfusion; remote ischemic preconditioning in hypoxic rats (HAR). Each group was randomized into two subgroups: control and renal I/R (45 min occlusion of left renal artery subsequent 4 hr reperfusion). Western blotting of HO-1 protein expression and HO activity measurement revealed significant increases in HA, SLR and HAR groups compared with the SL group. HO-1 antagonist, ZnPP Ⅸ was administered to check the changes of renal function. Renal functions were assessed by urine flow rate, urine sodium excretion, glomerular filtration rate (GFR) and renal blood flow. Renal function of rats undergoing I/R in SLR, HA and HAR were better than SL.
The data suggest that HA and remote ischemic precondition enhanced renal HO-1 protein production and HO activity. The increase of HO-1 may play a role to protecting the rat kidney from I/R injury.
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