[Protective effect of early application of lytic cocktail on small intestine of severely scalded rats].
OBJECTIVE
To study the protective effect of early application of lytic cocktail on small intestine of severely scalded rats.


METHODS
Sixty-six male SD rats were divided into sham injury group (SI, n=6), scald group (S, n=30) and scald+lytic cocktail group (SL, n=30) according to the random number table. After anesthesia, rats in the latter 2 groups were inflicted with 30% full-thickness scald, while rats in S group were sham scalded with 37 degrees C water. Resuscitation was carried out by intraperitoneal injection with 2 mLxkg(-1)x%TBSA(-1) lactated Ringer's solution in all rats; meanwhile 12 mL/kg lytic cocktail [1 mL pethidine (50 mg/mL)+1 mL chlorpromazine (25 mg/mL)+1 mL promethazine (25 mg/mL)+125 mL saline] was hypodermically injected to rats in SL group, while 12 mL/kg saline was injected into rats in the other 2 groups. Samples of blood and small intestine were harvested from S and SL groups at post scald hour (PSH) 3, 6, 12, 24, 48 and from SI group at PSH 3, with 6 rats in each group at each time point. Pathological changes in intestine were observed, and the expression of intercellular adhesion molecule 1 (ICAM-1) and CD68 were determined with immunohistochemistry at PSH 24 for S and SL groups and at PSH 3 for SI group. Plasma levels of D-lactate, diamine oxidase (DAO), IL-1beta, TNF-alpha, IL-10 were determined with ELISA. Data were processed with one-way analysis of variance.


RESULTS
(1) At PSH 24, mild hemorrhage, inflammatory cell infiltration and epithelial cell shedding were observed in small intestinal mucosa of rats in S group. Compared with S group, the intestinal villi of SL group were arranged regularly without obvious hyperemia and edema. (2) Expression levels of ICAM-1 and CD68 [(1.69+/-0.27)%, (0.80+/-0.09)%] in S group were significantly higher than those in SI group [(0.77+/-0.10)%, (0.30+/-0.05)%, with F value respectively 77.303 and 66.933, P<0.05 or P < 0.01] and SL group [(0.53+/-0.09)%, (0.32+/-0.06)%, with F value respectively 77.303 and 66.933, P values all below 0.01]. (3) D-lactate levels of rats in SL group were significantly lower than those of rats in S group at PSH 12, 24 (with F value respectively 20.936 and 19.854, P values all below 0.01), while DAO levels of rats in SL group were significantly lower than those of rats in S group at PSH 3, 12 (with F value respectively 21.930 and 11.342, P values all below 0.05). (4) The levels of IL-1beta and TNF-alpha in S group were significantly higher than those of SI group at each time point (P values all below 0.01). The levels of IL-1beta and TNF-alpha in SL group were significantly higher than those of S group at PSH 6, 12 and 24 (with F value respectively 96.517, 17.365, 79.715 and 21.328, 17.682, 28.424, P<0.05 or P<0.01). IL-10 level in SL group was higher than that in S group at each time point, and the differences were statistically significant at PSH 6 and 24 (with F value respectively 8.668, 19.634, P < 0.05 or P<0.01).


CONCLUSIONS
Early administration of lytic cocktail can attenuate edema and injury of intestinal mucosa in severely scalded rats. The mechanism may lie in that it can reduce the expression of ICAM-1 in intestinal mucosa, decrease the number of intestinal inflammatory cells and regulate the levels of inflammatory cytokines.
Shao
Qing-bo
QB
Department of Burns and Plastic Surgery, Ruijin Hospital, Medical College of Shanghai Jiao Tong University, Shanghai 200025, China.
Zhang
Xiong
X
Chen
Xue-lian
XL
Liu
Yan
Y
Zhang
Qin
Q
Liao
Zhen-jiang
ZJ
D000818:Animals; D002056:Burns / Q000628:therapy*; D002746:Chlorpromazine / Q000494:pharmacology; D004338:Drug Combinations; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology*; D007421:Intestine, Small / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008614:Meperidine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D004338:Drug Combinations; D014409:Tumor Necrosis Factor-alpha; D008614:Meperidine; D002746:Chlorpromazine