[Isoflurane produces delayed preconditioning against renal ischemia/reperfusion injury via hypoxia inducible factor 1 alpha activation].
OBJECTIVE
Isoflurane has an acute preconditioning effectiveness against ischemia in kidney, but this beneficial effectiveness can only last for 2-3 hours. To investigate whether isoflurane produces delayed preconditioning against renal ischemia/reperfusion (I/R) injury, and whether this process is mediated by hypoxia inducible factor 1 alpha (HIF-1 alpha).


METHODS
A total of 52 male C57BL/6 mice were randomly assigned to 4 groups (n=13 in each group): the control group (group A), PBS/isoflurane treated group (group B), scrambled small interference RNA (siRNA)/isoflurane treated group (group C), and HIF-1 alpha siRNA/isoflurane treated group (group D). In groups C and D, 1 mL RNase-free PBS containing 50 microg scrambled siRNA or HIF-1 alpha siRNA was administered via tail vein 24 hours before gas exposure, respectively. Equivalent RNase-free PBS was given in groups A and B. Then the mice in groups B, C, and D were exposed to 1.5% isoflurane and 25% O2 for 2 hours; while the mice in group A received 25% O2 for 2 hours. After 24 hours, 5 mice in each group were sacrificed to assess the expressions of HIF- 1 alpha and erythropoietin (EPO) in renal cortex by Western blot. Renal I/R injury was induced with bilateral renal pedicle occlusion for 25 minutes followed by 24 hours reperfusion on the other 8 mice. At the end of reperfusion, the serum creatinine (SCr), the blood urea nitrogen (BUN), and the histological grading were measured.


RESULTS
The expressions of HIF-1 alpha and EPO in groups B and C were significantly higher than those in group A (P < 0.01). The concentrations of SCr and BUN in groups B and C were significantly lower than those in group A, as well as the scores of tubules (P < 0.01), and the injury of kidney was ameliorated noticeably in groups B and C. The expressions of HIF-1 alpha and the concentrations of SCr and BUN in group D were significantly lower than those in group A (P < 0.01). Compared with groups B and C, the expression of HIF-1 alpha and EPO in group D decreased markedly (P < 0.01), the concentrations of SCr and BUN were increased obviously, as well as the scores of tubules (P < 0.01), and the renal injury was aggravated significantly.


CONCLUSIONS
Isoflurane produces delayed preconditioning against renal I/R injury, and this beneficial effectiveness may be mediated by HIF-1 alpha.
Cheng
Jian
J
Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P.R. China.
Zhang
Lei
L
Huang
Han
H
Ma
Daqing
D
Liu
Jin
J
D000818:Animals; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D019194:Ischemic Preconditioning; D007530:Isoflurane / Q000494:pharmacology*; D007668:Kidney / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015427:Reperfusion Injury / Q000517:prevention & control*
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007530:Isoflurane