Effect of Efferent Vagus Nerve Excitation by Electrical Stimulation on Acute Liver Injury in Rabbits with Endotoxemia

Objective:To study the effect of electrical stimulation of efferent vagus nerve on the acute liver injury induced by endotoxemia in rabbits. Methods:Sixteen rabbits were randomly divided into stimulation group(Group A,n=8) and control group (Group B,n=8).They were subjected to bilateral cervical vagotomy and intravenously challenged by lipopolysaccharide (LPS) (E.coli 0111:B4,DIFCO,USA) at a dose of 100 μg/kg injected within 30 min.The distal end of the left vagus nerve trunk was placed across bipolar electrodes connected to a stimulation module and controlled by an acquisition system.Stimuli with constant voltage (10V,5Hz,5ms) were applied twice to the nerve for 10 min before and after the administration of LPS in Group A.At the time 30,60,120,180,240,300 min before and after infusion of LPS respectively in each animal,blood samples were taken for late measurement of the serum Alanine aminotransferase (ALT),Aspartate aminotransferase (AST),tumor necrosis factor-α(TNF-α) and interleukin-10 (IL-10).Immediately after the experiment was finished,autopsy was performed and liver samples were taken to pathologic study. Results:Compared with Group B,the electrical stimulation of efferent vagus nerve could significantly decrease the contents of ALT,AST and TNF-α,but increase the contents of IL-10,in serum of Group A.It could also alleviate inflammation of liver tissue after LPS attack. Conclusion:The results suggest that excitation of the efferent vagus nerve can inhibit the inflammation cascade in liver after LPS challenge.Thus,it might have a protective effect on acute liver damage caused by endotoxemia.

Effect of NS-398 on colon cancer cells

AIM: To study the effect of NS-398, a selective cydooxygenase 2 (COX-2) inhibitor, on invasion of colon cancer cell line HT-29 in vitro and to explore its mechanisms. METHODS: Invasive behaviors of the malignant colon cancer cell line HT-29 were investigated in this study. Expressions of COX-2 and CD44v6 in HT-29 cells were detected by flow cytometry. Cellular survival rate was determined by MTT assay. The invasive capacity was quantified by a modified Boyden chamber model. Alterations of cytoskeleton component F-actin were observed by confocal laser scanning microscope. RESULTS: Flow cytometry analysis showed that COX-2 was highly expressed in HT-29 cells. The invasive capability of HT-29 cells could be greatly inhibited by NS-398 at the experimental concentrations of 0.1,1.0 and 10 μmol/L with an inhibitory rate of 22.74%, 42.35% and 58.61% (P<0.01), respectively. MTT assay showed that NS-398 at the experimental concentrations had no significant influence on cellular viability, indicating that such anti-invasive effects had no relationship with cytotoxicity. F-actin was mainly distributed around nuclei forming annular structure in HT-29 cells. After exposure to NS-398 of 10 μmol/L, the annular structure around nuclei disappeared and the fluorescence intensity of F-actin decreased obviously. Treatment with NS-398 could down-regulate the expression of CD44v6 as well. CONCLUSION: NS-398 has anti-invasive effects on colon cancer HT-29 cells in vitro, which may be mediated by a novel mechanism of disruption of cytoskeleton. Down-regulation of CD44v6 expression may be related to alterations of cytoskeleton.