Study on the expression and roles of nucleolin in cardiac injury in septic mice

Abstract

Objective: To explore the expression and roles of nucleolin in cardiac injury in septic mice. Methods: C57BL/6 mice (WT mice) and myocardium-specific expression of nucleolin transgenic mice (TG mice) were randomly divided into sham group (n=10, sham-operated) and sepsis group (n=15, animal model). Cecal ligation and puncture (CLP) was adopted to produce animal models of sepsis. The expression of nucleolin was detected by Western blotting analysis at 0, 12, 24, 48 hours after the operation. The 7-day survival rate, haemodynamic measurement, levels of isoenzyme of creatinekinase-MB (CK-MB) and cardiac troponin I (cTnI) in serum and levels of reactive oxygen species (ROS) and malondlaldehyde (MDA) in myocardium were evaluated 24 hours after the operation. The data were compared between groups with t test. Results: The expression of nucleolin in myocardium up-regulated significantly in WT+CLP group when compared with that in the WT+Sham group(2.57±0.34 vs 1.00±0.15, t=7.468, P<0.01). Compared with those in the WT+Sham group, the survival rate decreased (33.3% vs 100%, χ(2)=13.375, P<0.01), maximal rate of pressure development (+dp/dtmax) declined (t=4.993, P<0.01), but the serum levels of CK-MB and cTnI and the levels of ROS and MDA in myocardium increased in the WT+CLP group(t=5.031, 4.335, 3.365, 2.375, all P<0.05). Compared with that in WT+CLP group, the 7-day survival rate of mice increased in TG+CLP group (60.0% vs 33.3%, χ(2)=8.227, P=0.004), and the cardiac function improved (t=2.337, P=0.019), but the serum levels of CK-MB and cTnI and the levels of ROS and MDA in myocardium in TG+CLP group reduced significantly (t=2.127, 3.347, 2.115, 2.224,P<0.05). Conclusion: The expression of nucleolin is up-regulated in the myocardium of septic mice, and the overexpression of nucleolin can inhibit oxidative stress injury, attenuate the cardiac injury and dysfunction, and reduce mortality in septic mice.