- 作者: Asma Mahfoudh-Boussaid, Mohamed Amine Zaouali, Kaouther Hadj-Ayed, Abdel-Hedi Miled, Dalila Saidane-Mosbahi, Joan Rosello-Catafau and Hassen Ben Abdennebi
- 作者服務機構: Laboratory of human physiology, faculty of pharmacy, university of Monastir, Tunisia.
- 中文摘要: --
- 英文摘要:
Background: Although recent studies indicate that renal ischemic preconditioning (IPC)
protects the kidney from ischemia-reperfusion (I/R) injury, the precise protective mechanism
remains unclear. In the current study, we investigated whether early IPC could upregulate
hypoxia inducible transcription factor-1α (HIF-1α) expression and could reduce endoplasmic
reticulum (ER) stress after renal I/R and whether pharmacological inhibition of nitric oxide
(NO) production would abolish these protective effects. Methods: Kidneys of Wistar rats
were subjected to 60 min of warm ischemia followed by 120 min of reperfusion (I/R group),
or to 2 preceding cycles of 5 min ischemia and 5 min reperfusion (IPC group), or to
intravenously injection of NG-nitro-L-arginine methylester (L-NAME, 5 mg/kg) 5 min before
IPC (L-NAME+IPC group). The results of these experimental groups were compared to those
of a sham-operated group. Sodium reabsorption rate, creatinine clearance, plasma lactate
dehydrogenase (LDH) activity, tissues concentrations of malonedialdehyde (MDA), HIF-1α
and nitrite/nitrate were determined. In addition, Western blot analyses were performed to
identify the amounts of Akt, endothelial nitric oxide synthase (eNOS) and ER stress
parameters.
Results: IPC decreased cytolysis, lipid peroxidation and improved renal function. Parallely,
IPC enhanced Akt phosphorylation, eNOS, nitrite/nitrate and HIF-1α levels as compared to
I/R group. Moreover, our results showed that IPC increased the relative amounts of glucoseregulated
protein 78 (GRP78) and decreased those of RNA activated protein kinase (PKR)-
like ER kinase (PERK), activating transcription factor 4 (ATF4) and TNF-receptor-associated
factor 2 (TRAF2) as judged to I/R group. However, pre treatment with L-NAME abolished
these beneficial effects of IPC against renal I/R insults.
Conclusion: These findings suggest that early IPC protects kidney against renal I/R injury via
reducing oxidative and ER stresses. These effects are associated with phosphorylation of Akt, eNOS activation and NO production contributing thus to HIF-1α stabilization. The beneficial
impact of IPC was abolished when NO production is inhibited before IPC application. - 中文關鍵字: --
- 英文關鍵字: kidney; ischemia-reperfusion; ischemic preconditioning; Akt; eNOS, HIF1-α; ER stress;