ABSTRACT
Objective:
To evaluate the
role of
cold-inducible
RNA-binding protein (CIRP) in
acute renal injury in a
mouse model of
myocardial ischemia-
reperfusion (I/R) and the relationship with
nuclear factor kappa B (NF-κB) signaling pathway.
Methods:
Twenty-four SPF-grade healthy
male C57BL/6
mice,
aged 6-8 weeks, with
body mass index of 24-28 g, were divided into 3 groups ( n=8 each) using a random number table
method:
sham operation group (Sham group), myocardial I/R group (I/R group) and myocardial I/R + CIRP-derived
peptide C23 group (I/R+ C23 group). The model of myocardial I/R was developed by
ligation of the left anterior descending
coronary artery for 30 min followed by 120-min
reperfusion in anesthetized
animals. CIRP-derived
peptide C23 8 mg/kg was intraperitoneally injected before
myocardial ischemia and
reperfusion in I/R+ C23 group, while Sham group was only threaded without
ligation.
Blood samples were collected from the right
internal carotid artery at 120 min of
reperfusion for
determination of the
serum creatine kinase isoenzymes (CK-MB), lactic
dehydrogenase (LDH),
creatinine (Cr) and
blood urea nitrogen (
BUN) concentrations. Renal
tissues were obtained for examination of the pathological changes, and the tubular
injury score was assessed. The expression of NF-κB, phosphorylated NF-κB (p-NF-κB),
Nod-like receptor protein 3 (NLRP3),
interleukin-1beta (
IL-1β) and
IL-18 in renal
tissues was detected by
Western blot. The expression of
Toll-like receptor 4 (TLR4), NLRP3,
IL-1β, TNF-α and
IL-6 mRNA was determined by
real-time polymerase chain reaction.
Results:
Compared with Sham group, the levels of
serum CK-MB, LDH, Cr and
BUN and renal tubule
injury score were significantly increased, the expression of p-NF-κB, NLRP3,
IL-1β and
IL-18 was up-regulated, the expression of TLR4, NLRP3,
IL-1β, TNF-α and
IL-6 mRNA was up-regulated ( P<0.05), and the pathological
injury to renal
tissues was aggravated in I/R group. Compared with I/R group, the
serum CK-MB, LDH, Cr,
BUN and renal tubular
injury score were significantly decreased, and the expression of p-NF-κB, NLRP3,
IL-1β and and
IL-18 was down-regulated, the expression of TLR4, NLRP3,
IL-1β, TNF-α and
IL-6 mRNA was down-regulated ( P<0.05), and the pathological
injury to renal
tissues was alleviated in I/R+ C23 group.
Conclusions:
CIRP is involved in the process of
acute renal injury in a
mouse model of myocardial I/R, which is associated with activation of NF-κB signaling pathway and promotion of inflammatory responses.