- 作者: Jia Y Guo, Tong Yang, Xiang G Sun, Ni Y Zhou, Fu S Li, Dan Long, Tao Lin, Ping Y Li and Li Feng
- 作者服務機構: Key Laboratory of Transplant Engineering and Immunology of Health Ministry of China, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, Mainland China
- 中文摘要: --
- 英文摘要:
Background: Ischemic postconditioning (IPO) has been demonstrated to attenuate
ischemia/reperfusion (I/R) injury in the heart and brain, its roles to liver remain to be defined. The
study was undertaken to determine if IPO would attenuate liver warm I/R injury and its protective
mechanism.
Methods: Mice were divided into sham, I/R, IPO+I/R (occlusing the porta hepatis for 60 min,
then treated for three cycles of 10 sec brief reperfusion consecutively, followed by a persistent
reperfusion); L-NAME+ sham (L-NAME, 16mg/kg, i.v., 5 min before repefusion); L-NAME+I/R;
and L-NAME+ IPO. Blood flow of caudate and left lobe of the liver was blocked. Functional and
morphologic changes of livers were evaluated. Contents of nitric oxide, eNOS and iNOS in serum
were assayed. Concentration of eNOS, iNOS, malondialdehyde (MDA) and activity of superoxide
dismutase (SOD) in hepatic tissue were also measured. Expressions of Akt, p-Akt and HIF-1α
protein were determined by western blot. Expressions of TNF-α and ICAM-1 were measured by
immunohistochemistry and RT-PCR.
Results: IPO attenuated the dramatically functional and morphological injuries. The levels of ALT
was significantly reduced in IPO+I/R group (p<0.05). Contents of nitric oxide and eNOS in serum
were increased in the IPO+I/R group (p<0.05). IPO also up-regulated the concentration of eNOS,
activity of SOD in hepatic tissue (p<0.05), while reduced the concentration of MDA (p<0.05).
Moreover, protein expressions of HIF-1α and p-Akt were markedly enhanced in IPO+I/R group.
Protein and mRNA expression of TNF-α and ICAM-1 were markedly suppressed by IPO (p
<0.05). These protective effects of IPO could be abolished by L-NAME.
Conclusions: We found that IPO increased the content of NO and attenuated the overproduction
of ROS and I/R-induced inflammation. Increased NO contents may contribute to increasing
HIF-1α level, and HIF-1α and NO would simultaneously protect liver from I/R injury. These
findings suggested IPO may have the therapeutic potential through Akt-eNOS-NO-HIF pathway
for the better management of liver I/R injury. - 中文關鍵字: --
- 英文關鍵字: --