乌司他丁对严重烧伤后多脏器功能的保护作用

目的观察乌司他丁对严重烧伤后多个重要脏器功能的保护作用。方法贵州三系雄性小型猪12只,随机分为A组(烧伤对照组,n=6)、B组(UTI治疗组,n=6)两组,造成35%Ⅲ度烧伤,其中A、B两组动物于烧伤前各随机选取4只抽取静脉血作为正常对照。B组动物于伤后1h给予UTI5000U/kg,A组动物给予等量生理盐水,3次/d。分别于动物烧伤前、伤后6、24、48、72h抽血进行血清DAO活性、TNF-α、IL-6、D-乳酸、MDA、SOD、ALT、AST、CK、CKMB、LDH、BUN、Cr含量检测;北京积水潭医院烧伤科2002年5月至2004年12月期间收治的烧伤面积50%~70%深Ⅱ度~Ⅲ度,Ⅲ度>30%患者40例,随机分为常规治疗组(n=16)和UTI治疗组(n=24),16名青壮年志愿者为正常对照组。两组病人均进行常规抗休克、创面处理和营养治疗。UTI组病人经静脉滴注UTI40万U,2次/d,常规组病人给予等容量的生理盐水,连续用药7d。观察伤后48h平均体温、脉搏、呼吸、血压(收缩压)、伤后48h总补液量、每小时尿量、并发症、死亡率;伤后第1、3、7天进行血清LPS、TNF-α、MPO、NE及ALT、AST、CK、CKMB、LDH、BUN、Cr含量检测。结果严重烧伤后动物血清TNF-α、IL-6、D-乳酸、MDA、ALT、AST、CK、CKMB、LDH、BUN、Cr含量明显升高,SOD显著减少。以A组尤为明显(P<0·05)。伤后6、24、48、72h,A组血清TNF-α(pg/L)分别为137±14、254±10、202±28、183±15,B组分别为86±15、177±19、152±15、138±20,A组血清IL-6(pg/L)分别为296±25、524±42、422±57、373±17,B组分别为180±32、388±45、332±40、296±42。A组血清MDA(nmol/ml)分别为5·6±0·7、6·4±0·4、4·9±0·5、4·8±1·0,B组分别为3·6±0·4、3·4±0·5、3·1±0·3、3·0±0·3。A组血清SOD(nU/ml)分别为53±13、54±7、36±7、36±8,B组分别为81±11、71±14、55±9、63±9。A组动物血清ALT、AST、CK、CKMB、LDH、BUN、Cr、D-乳酸含量和DAO活性于各时间点均较B组显著升高(P<0·05)。所有患者烧伤后血LPS、TNF-α、NE、MPO、ALT、AST、CK、CK-MB、BUN、Cr明显增高,UTI治疗组各指标显著下降。伤后1、3、7d,常规组血LPS(μg/L)分别为26±12、94±35、44±17,UTI组分别为23±10、68±22、39±16,常规组血TNF-α(μg/L)分别34±5、114±13、66±7,UTI组分别为24±5、93±13、57±6,常规组血NE(pg/L)分别为637±100、1052±33、809±88,UTI组分别为429±48、888±99、602±68。UTI组患者全部治愈,无并发症发生。常规治疗组有2例脓毒症,1例因MOF死亡。结论乌司他丁能显著抑制炎性介质及中性粒细胞蛋白酶的释放和氧自由基产生,减轻烧伤后脏器功能损害程度。

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. CONCLUSION: UTI can significantly lessen the production of inflammatory mediators and oxygen free radical and protect the functions of multiple organs after severe burn.