乌司他丁对内毒素休克大鼠器官功能的保护作用

The Protective Effects of Ulinastatin on Organ Dysfunction induced by Lipopolysaccharide in Rat Shock

目的探讨蛋白酶抑制剂对于内毒素所致大鼠休克时器官功能的保护作用及其可能的机制。方法健康雄性Wistar大鼠共48只,分为两部分,每一部分24只,分为三组。其中第一部分设:生理盐水对照组(C组,n=6);内毒素组(E组,n=10),尾静脉注射内毒素5mg/kg(lipopolysaccharide,LPSO55:B5);蛋白酶抑制剂组(U组,n=8),尾静脉给与LPS5mg/kg,同时分别给予腹腔注射蛋白酶抑制剂乌司他丁10万U/kg。第二部分三组给药方法相同,不取组织和血标本,仅观察2h血压及24h死亡率。第一部分三组动物2h采集血、尿标本及肺组织,分别测定肺组织湿/干重比值及髓过氧化物酶(MPO)、脂质过氧化代谢产物水平(丙二醛MDA和共轭二烯C-diense),测定动脉血气、血乳酸(Lactic acid)和内皮素(ET)水平、血浆肌酐(SCr)及尿N-乙酰氨基葡萄糖苷酶(NAG)水平。结果U组血压低于C组〔(99.16±6.91vs120.5±3.41)mmHg〕(P<0.001)而高于E组〔(99.16±6.91vs75±4.16)mmHg〕(P<0.001);血气分析示PaO2U组高于E组〔(112.8±4.83vs82.8±4.03)mmHg〕(P<0.01);肺湿/干重U组明显低于E组(5.0±0.05vs5.41±0.06)(P<0.001);肺组织MPO活性,U组明显低于E组〔(119.40±11.32vs152.90±8.41)u/g.w.w〕(P<0.001),肺组织脂质过氧化物水平U组较E组明显降低〔(MDA51.26±5.56vs73.95±4.62;C-diense7.59±0.84vs10.96±0.81)nmol/g.w.w〕(P<0.01);尿NAG与血浆肌酐水平U组明显低于E组分别为〔(122.56±14.33vs337.67±16.52)IU/L及(56.21±4.77vs115.67±5.95)μmol/L〕(P<0.001);血浆乳酸水平U组较E组降低〔(4.03±0.11vs5.90±0.14)mmol/L〕(P<0.001);血浆内皮素水平U组较E组降低〔(633.27±93.27vs948.23±103.45)pg/ml〕(P<0.05),U组大鼠死亡率有下降趋势。结论蛋白酶抑制剂乌司他丁对内毒素所致休克大鼠的多器官功能损害具有一定的保护作用。

Objective To investigate the efffects of protease inhibitor Ulinastatin on lipopolysaccharide-induced multiple organ dysfunction in rats and its possible mechanisms. Methods 48 male Wistar rats were divided into two parts, first divided into three groups randomly: C: control group (n=6); E: endotoxin group (n=10), receiving intravenous endotoxin (lipopolysaccharide O55:B5, LPS 5mg/kg); U: Ulinastatin intervention group (n=8), receiving intraperitoneal Ulinastatin10万U/kg and LPS 5mg/kg. the same with the second part for dividing groups but only observed the mortality without given any medicaments. Collect specimens at 2 hour in first part, We observed the following changes: blood gas analysis, the lung wet/dry weight ratio, lung tissue myeloperoxidase activity, plasma endothelin-1, lung tissue lipid-peroxide, serum lactic acid , Serum creatinine (Scr)and N-acetyl-β-glucosaminidase (NAG)in urine, the mortality rate at 24 hour. Results BP of E and U group decreased significantly than C group, U group higher than E group(respectively, P<0.001); Blood gas analysis showed that PaO2 decreased significantly in E than U group(P<0.01). The lung wet/dry weight ratio increased significantly in E than U group (P<0.001). Lung tissue myeloperoxidase (MPO)activity increased significantly in E group than U group (P<0.001). The plasma endothelin-1 (ET-1)decreased significantly in U group than E group (P<0.05), Lipid peroxide(malonaldehyde and C-diense) in lung tissue decreased significantly in U group than E group (P<0.01). The blood lactic acid decreased significantly in U group than E group (P<0.001). Serum creatinine and NAG in urine decreased significantly in U group than E group (P<0.001).Mortality decreased but not significantly. Conclusion The protease inhibitor, Ulinastatin, may develop protective on multiple organ dysfunction in sepsis.