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[Study of the change and role of protein C system in ulcerate colitis.] [Article in Chinese]

LIN Xu-Hong, WANG Hui-Chao, WEI Dan-Dan, WANG Bin, GE Quan-Xing, BAI Chun-Yang, WANG Ya-Qiang, REN Xue-Qun

Department of Clinical Laboratory, Huaihe Hospital Affiliated to Henan University, Kaifeng 475000, China； Department of Nephrology, the First Hospital Affiliated to Henan University, Kaifeng 475000, China； Department of Digestive Medicine, Huaihe Hospital Affiliated to Henan University, Kaifeng 475000, China； Department of General Surgery, Huaihe Hospital Affiliated to Henan University, Kaifeng 475000, China

Abstract

Hypercoagulable state and thrombosis are major lethal causes of ulcerate colitis (UC). The aim of the present study is to explore the change and role of protein C (PC) system in UC thrombosis. 4% dextran sulfate sodium (DSS) was used to induce the UC model, and the body weight, the length of colon, and the weight of spleen were measured after intake of DSS as drinking water for 1 week. The macroscore and microscore were examined. The quantity of macrophage in colon smooth muscle was observed by immunofluorescence, and TNF-α and IL-6 levels in plasma were evaluated by ELISA. Intravital microscopy was applied to observe colonic mucosal microvascular circulation, activities of PC and protein S (PS) were determined by immunoturbidimetry, endothelial cell protein C receptor (EPCR) and thrombomodulin (TM) expressions were detected by immunohistochemistry. In vitro, TNF-α and IL-6 levels were tested in supernatant of macrophage separated from colonic tissue. After stimulation of mouse colonic mucosa mocrovascular endothelial cells by TNF-α and IL-6 respectively, the activities of PC, PS, activated protein C (APC) were evaluated, and the expressions of EPCR and TM were detected by Western blotting. The results revealed that the DSS mouse showed weight loss (P < 0.05), a shorten colon (P < 0.05), and swelled spleen (P < 0.05), accompanied by higher histological score (P < 0.05), as well as infiltration of macrophages, elevated TNF-α and IL-6 levels in plasma (P < 0.01). The intravital microscopy results revealed that compared with control, DSS mice showed significantly enhanced adhesion of leukocytes and colonic mucosal microvascular endothelial cells (P < 0.01), meanwhile, activity of PC and PS decreased obviously in plasma (P < 0.01 or P < 0.05), and expression of EPCR was down regulated. The degree of inflammation was negatively correlated with the PC activity. In vitro, TNF-α and IL-6 level were increased in the supernatant of macrophages from DSS mice colonic tissue (P < 0.05), and after incubation of TNF-α or IL-6 with colonic mucosal microvascular endothelial cells, the APC activity was decreased (P < 0.05 or P < 0.01), and expression of EPCR was down regulated (P < 0.05). These results suggest that PC system is inhibited in UC mouse. Presumably, the mechanism may be due to the secretion of cytokines from macrophages and subsequential influence on the function of endothelia cells. Furthermore, enhancement of PC system activity may serve as a new target for the treatment of UC.

Key words: protein C system; ulcerate colitis; thrombosis

Received: 2014-10-09　　Accepted: 2014-12-24

Corresponding author: 任学群　　E-mail: hhyyrxq@126.com

Citing This Article：

LIN Xu-Hong, WANG Hui-Chao, WEI Dan-Dan, WANG Bin, GE Quan-Xing, BAI Chun-Yang, WANG Ya-Qiang, REN Xue-Qun. [Study of the change and role of protein C system in ulcerate colitis.] [Article in Chinese]. Acta Physiol Sin 2015; 67 (2): 201-206 (in Chinese with English abstract).