[Protective effects of ulinastatin against multiple organic damage after severe burn injury: experimental and clinic studies].
OBJECTIVE
To study the protective effects of ulinastatin (UTI), a human trypsin inhibitor, on the damage to the functions of multiple organs at the early stage of severe burn.


METHODS
(1) Twelve male mini-pigs, inflicted with III degrees burn with 35% total body surface area (TBSA), were randomly divided into two equal groups: Group A (control group, treated with fluid resuscitation immediately after injury and normal saline by intravenous drip tid) and Group B (UTI-treated group, in addition to fluid resuscitation UTI 5000 U/kg was given one hour after injury, 3 times/day). Blood samples were taken for the determination of serum TNF-alpha, IL-6, malonyldiadehyde (MDA), superoxide dismutase (SOD), alanine transaminase (ALT), aspartate transaminase (AST), creatine kinase (CK), MB isoenzyme of CK (CK-MB), blood urea nitrogen (BUN), creatinine (Cr), diamine oxidase (DAO), and D-lactate before and 6, 24, 48, and 72 hours after injury. (2) Forty hospitalized patients with 50%-70% TBSA partial and full thickness burn, 28 males and 12 females, aged 18-60, were randomly divided into routine treatment group (n = 16, receiving routine fluid resuscitation and wound management and normal saline IV drop bid for 7 days) and UTI treatment group (n = 24, in addition to the routine treatment UTI 400,000 U was given IV drop bid for 7 days). Sixteen healthy volunteers served as controls to undergo blood examination. The average body temperature (T), respiratory rate (R), systole blood pressure (BP) were detected 48 hours after burn. Blood samples were taken to determine the plasma lipopolysaccharide (LPS), and serum TNF-alpha, norepinephrine (NE), myeloperoxidase (MPO), ALT, AST, CK, CK-MB, lactic dehydrogenase (LDH), BUN, and Cr 1, 3, and 7 days after burn.


RESULTS
(1) The serum TNF-alpha, IL-6, and MDA levels significantly increased, and the serum SOD level significantly decreased 6 hours after burn in the mini-pings in both groups (all P < 0.05), and the changes in Group A were more significant than in Group B (all P < 0.05). The serum AST, CK, CK-MB, BUN, Cr, DAO, and D-lactate levels increased in the mini-pigs of both groups after severe burn in comparison with those before burn (all P < 0.05), especially in Group A in comparison with Group B (all P < 0.05). However, the serum levels of ALT and LDH of Group B did not increase significantly in comparison with those before burn. (2) The serum LPS, TNF-alpha, NE, ALT, AST, CK, CKMB, LDH, BUN, Cr, and MPO significantly increased after burn and began to decrease since the 7th day after burn, and the decrease levels in the UTI group were more significant than in the routine treatment group (all P < 0.05). In the routine treatment group 2 cases of sepsis were found and one case died of multiple organ failure; no complication was found in the UTI treatment group.


CONCLUSIONS
UTI can significantly lessen the production of inflammatory mediators and oxygen free radical and protect the functions of multiple organs after severe burn.
Hu
Xiao-hua
XH
Department of Burns, Beijing Jishuitan Hospital, Beijing 100035, China.
Zhang
Hui-ying
HY
Ge
Yan-ling
YL
Chen
Zhong
Z
Qin
Feng-jun
FJ
Jiang
Hai-yan
HY
Chen
Da-fu
DF
Sun
Yong-hua
YH
D000293:Adolescent; D000328:Adult; D000818:Animals; D002056:Burns / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D005260:Female; D006023:Glycoproteins / Q000627:therapeutic use*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides / Q000097:blood; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000097:blood / Q000517:prevention & control*; D020011:Protective Agents / Q000627:therapeutic use; D013482:Superoxide Dismutase / Q000097:blood; D013552:Swine; D013556:Swine, Miniature; D014361:Trypsin Inhibitors / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D006023:Glycoproteins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D020011:Protective Agents; D014361:Trypsin Inhibitors; D014409:Tumor Necrosis Factor-alpha; D013482:Superoxide Dismutase; C028665:urinastatin