The mechanisms of LPS-induced cardiac dysfunction in septic mice

Objective To study about the cardiac function of the mice suffering from sepsis induced by lipopolysaccharide (LPS) so as to probe the physiopathologic mechanism of the cardiac dysfunction of the mice. Method Sixty male C57BL/6 mice of eight weeks old were randomly (random number) divided into four groups: one control group (n=15) and three experimental groups (n=15 in each group). The mice of control group received intra-peritoneal injection of normal saline (10 mg/kg) while the mice of experimental groups got intra-peritoneal injection of LPS (10 mg/kg). The cardiac function of mice (n=12) was determined by echocardiography 6 h, 12 h and 24 h later, respectively. The heart, kidney and lung tissues of mice (n=6) were stained with Haematoxylin-Eosin (HE) staining after embedding with paraffin for observing the histopathological changes under optic microscopy. The expressions of PECAM-1 and α-SMA of the heart tissue of mice (n=3) in three groups determined by immunohistochemical method. The RT-PCR method was used to test the expressions of VEGF (vascular endothelial growth factor) and HIF-α (hypoxia-inducible factor) of the myocardium of mice. In addition, the Western blot method was employed to test the levels of p53 and HIF-1α proteins in myocardium of mice, while ELISA was utilized to detect the level of tumor necrosis factor-α (TNF-α) and the interleukin-6 (IL-6). The data were analyzed by independent samples of t-test and one-way ANOVA respectively. Results The experiment result proved that the thickness of anterior wall of left ventricle of mice during systolic and diastolic periods increased and the inner diameter of the left ventricle also increased during the diastolic period in mice of the experimental group, while the stroke volume decreased compared with the control group (P<0.05). The immunohistochemical method showed that the new vessels of the mice's heart in experimental groups increased compared with the control group (P<0.05). RT-PCR showed the expressions of VEGF and HIF-1α of the mice heart of experimental group increased (P<0.05) and Western blot showed the levels of HIF-1α and p53 proteins in experimental groups increased significantly compared with the control group. The experimental group had higher levels of VEGF, HIF-1α, and IL-6 were evidenced by using ELISA than those of the control group (P<0.05). Conclusions The lipopolysaccharide can lead to cardiac dysfunction. In this process, myocardium angiogenesis and apoptosis phenomenon coexists, as VEGF and HIF-1α participating in angiogenesis, whereas BAX and p53 playing a role in the process of apoptosis. Key words: Sepsis; Pathophysiological mechanism; Cardiac dysfunction; Angiogenesis; Apoptosis