The effect of ulinastatin on the small intestine injury and mast cell degranulation in a rat model of sepsis induced by CLP.
BACKGROUND
Sepsis could be initiated by the gastrointestinal tract injury and subsequent bacterial translocation. In the present experiment, we aimed to investigate effect of ulinastatin (UTI) on the small intestinal injury and bacterial translocation in septic rats and role of mast cells degranulation in its action.


METHODS
Fifty-four male Wistar rats were randomly divided into three groups: sham laparatomy, cecal ligation and puncture (CLP), and CLP plus UTI. CLP was used to develop septic rat model and UTI was administered to rats intraperitoneally (50,000 U/kg) 30 min prior to CLP operation. After CLP or sham operation, variable parameters were investigated in three subsets of animals. One subset was used for measurements of nitrite and nitrate (NO(x)) concentration in plasma at 1, 6, 12, 18, and 24h and levels of NO(x) and iNOS mRNA in the small intestine, RMCP-II released into the small intestinal lumen, bacterial translocation and morphologic changes at 24h. The other subsets were used for the small intestinal motility and microvascular in vivo at 24h.


RESULTS
Bacterial translocation, barrier injury, impaired motility and blood flow, mast cells degranulation of the small intestine in the CLP group were found more severe than that in the sham group. Elevated RMCP-II, NO(x), and iNOS mRNA levels were also detected in the CLP group. Application of UTI not only protected the small intestine from sepsis but also diminished changes of intestinal mast cells.


CONCLUSIONS
UTI can significantly ameliorate the small intestinal injury and subsequent bacterial translocation by inhibiting mast cells degranulation in septic rats.
Zhang
Yi-Jing
YJ
Department of Gastroenterology, Shandong Provincial Hospital of Shandong University, Jinan, PR China.
Li
Ming
M
Meng
Mei
M
Feng
Mei
M
Qin
Cheng-Yong
CY
D000818:Animals; D015550:Cell Degranulation / Q000187:drug effects*; D053818:Chymases / Q000378:metabolism; D004195:Disease Models, Animal; D005769:Gastrointestinal Motility / Q000187:drug effects; D006023:Glycoproteins / Q000494:pharmacology*; D007421:Intestine, Small / Q000187:drug effects* / Q000293:injuries / Q000473:pathology; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018805:Sepsis / Q000188:drug therapy* / Q000473:pathology; D019108:Tight Junctions / Q000648:ultrastructure; D014361:Trypsin Inhibitors / Q000494:pharmacology*
D006023:Glycoproteins; D012333:RNA, Messenger; D014361:Trypsin Inhibitors; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C083294:chymase 2; D053818:Chymases; C028665:urinastatin