Protective Effects of Remote Limb Preconditioning on Ischemia Reperfusion Injury in Rats Liver
Abstract
Keywords
References
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blinded review of ten representative slides (×400) (Table 2). The AI
values were higher in the IR, HIPC, and LIPC groups than in the SO
group (P<0.05). The highest AI was in the IR group, and there was
no significant difference between the HIPC and LIPC groups.
Table 2 Hepatocellular Apoptosis Index (%).
Group
SO
IR
HIPC
LIPC
F
P
N
AI (%)
92±0.16
64±1.57 1
94±0.4212
02±0.44 123
498
<0.0001
P<0.05,compared with the SO group; 2 P<0.05, compared with the IR
group; 3 P>0.05, compared with the HIPC group.
DISCUSSION
Recent studies have demonstrated that remote ischemic
preconditioning, a process for the use of a non-vital distant organ
temporarily rendered to short sublethal ischemic preconditioning, is
able to protect other organs from the subsequent ischemia reperfusion
injury. Transient remote vascular occlusion has been shown to
be protective of IR injury in the heart, kidney[9], and brain[10], the
most commonly used preconditioning vascular is femoral artery.
The mechanisms accounting for remote preconditioning have been
investigated extensively in the field of myocardial ischemia, such as
neural and humoral pathway[11,12], inflammatory mediator[13], and etc.
However, they have received much less attention in the field of liver.
In this study, we hypothesized that it may modulate hepatocellular
apoptosis to attenuate the hepatocyte injury.
The results of this study showed that serum alanine tranaminase
(ALT) and aspartate tranaminase (AST) increased significantly
after 30 min of ischemia which indicated hepatocyte function
was impaired, and much lower degree of these parameters in both
HIPC and LIPC groups showed protective effects of these two
interventions.
On the basis of previous studies, we knew that during reperfusion
large numbers of oxygen free radicals were generated and NF-
κB was activated afterwards which could increase the gene
transcription of many pro-inflammatory cytokines (such as TNF-α
and IL-1)[14,15]. TNF-α and other mediators activated many of the
proteins involved in apoptosis, such as the proteases caspase-3
and caspase-8, along with mitochondria cytochrome-C released
to the cytoplasm[16,17]. The cascade of events that started with
these substances led to DNA destruction and cell death. With
this in mind, we observed the liver tissue apoptosis by means of
TUNEL assay to confirm the DNA injury. The results affirmed our
hypothesis, but the protective pathway of remote preconditioning
needed investigating further.
In our studies, hindlimb preconditioning was induced by three
cycles of 10 min occlusion of the bilateral femoral arteries followed
with 10 min reperfusion; this was consistent with all previous
studies[18,19]. This was based on evidence that three cycles of 10 min
LIPC was more effective than a single cycle and a study indicated a
single cycle IPC did not reduce liver damage in patients undergoing
major liver resection[20].
In some previous animal experiments, external tourniquet was
used to occlude blood flow to the limb, but this method was much
commonly applied in big animals. Moreover, some researchers
found that the pressure of tourniquet needed to occlude the femoral
vessels could cause neuromuscular paralysis[21]. In this study, because
the limb artery of rat was very thin and the femoral pulse was not
© 2013 ACT. All rights reserved. 794
Zhang WX et al . Protective effects of remote limb preconditioning on ischemia reperfusion injury in rats liver
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