[Isoflurane produces delayed preconditioning against renal ischemia/reperfusion injury via hypoxia inducible factor 1 alpha activation].

Abstract

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.

CONCLUSION:

Isoflurane produces delayed preconditioning against renal I/R injury, and this beneficial effectiveness may be mediated by HIF-1 alpha.

• Authors: Jian Cheng, Lei Zhang, Han Huang, Daqing Ma, Jin Liu
• Journal: Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery (Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi) Vol. 24 Issue 4 Pg. 477-81 (Apr 2010) ISSN: 1002-1892 [Print] China
• PMID: 20459015 (Publication Type: English Abstract, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Hypoxia-Inducible Factor 1, alpha Subunit
• Isoflurane

Topics

• Animals
• Hypoxia-Inducible Factor 1, alpha Subunit (metabolism)
• Ischemic Preconditioning
• Isoflurane (pharmacology)
• Kidney (metabolism, physiopathology)
• Male
• Mice
• Mice, Inbred C57BL
• Reperfusion Injury (prevention & control)