蛋白酶抑制剂对内毒素致大鼠肾功能损害的保护作用  

Protective effect of protease inhibitor on renal function of rat challenged by lipopolysaccharide

作　　者：汪波[1] 陈旭岩[1] 熊辉[1] 李秀清[1] 田亚男[1] 高雨松[1] 刘新民[1] 

机构地区：[1]北京大学第一医院急诊科,100034

出　　处：《中国危重病急救医学》2005年第10期603-605,F0005,共4页Chinese Critical Care Medicine

基　　金：国家自然科学基金资助项目(30471915)

摘　　要：目的探讨蛋白酶抑制剂对内毒素所致大鼠肾功能损伤的作用及其可能机制。方法健康雄性Wistar大鼠32只,随机分为对照组(n=6),内毒素(LPS)组(n=10,静脉注射LPS5mg/kg),大剂量乌司他丁(UT)干预组(n=8,腹腔注射UT100kU/kg和LPS5mg/kg),小剂量UT干预组(n=8,腹腔注射UT50kU/kg和LPS5mg/kg)。给予LPS2h后用乌拉坦麻醉大鼠,测定动脉血气、血浆内皮素1(ET1)、乳酸、肌酐(Cr)水平;行肾组织病理学检查;穿刺膀胱取尿,测定N乙酰氨基葡萄糖苷酶(NAG)。结果LPS组动脉血pH值、动脉血氧分压(PaO2)、动脉血二氧化碳分压(PaO2)、剩余碱(BE)均明显低于对照组(P均<0.01);两个UT干预组动脉血pH值、PaO2、PaCO2和BE均明显高于LPS组(P<0.05或P<0.01)。LPS组血浆ET1水平明显高于对照组(P<0.01),两个UT干预组均明显低于LPS组(P均<0.01),两个UT干预组之间差异无显著性(P>0.05)。LPS组乳酸水平明显高于对照组(P<0.001);两个UT干预组均明显低于LPS组(P均<0.01);两个UT干预组间比较差异无显著性(P>0.05)。LPS组血浆Cr及尿NAG均较对照组明显升高(P均<0.01);两个UT干预组血浆Cr及尿NAG水平均较LPS组明显降低(P均<0.01),两个UT干预组间比较差异均无显著性(P均>0.05)。肾脏病理检查可见LPS组肾小球大致正常,而肾小管上皮细胞空泡变性,部分上皮细胞崩解、脱落,管腔扩张,两个UT干预组肾小管病理变化均较LPS组减轻,不同剂量组间形态差异无显著性。结论蛋白酶抑制剂UT能够减轻LPS所致的大鼠肾脏损伤。Objective To investigate the protective effects of protease inhibitor on lipopolysaccharide （LPS） -induced kidney injury in rats and its possible mechanism. Methods Thirty -two male Wistar rats were divided into four groups randomly： normal control （n= 6）; LPS group （n= 10）, receiving intravenous endotoxin （LPS, 055： BS, 5 mg/kg）; low-dose ulinastatin （UT） intervention group （n=8）, receiving intraperitoneal UT 50 000 U/kg and LPS 5 mg/kg as above; high -dose UT intervention group （n= 8）, UT 100 000 U/kg and LPS 5 mg/kg. The following examinations were carried out： blood gas analysis, kidney pathological changes, plasma endothelin - 1, plasma lactic acid, N - acetylglucosaminidase （NAG） in urine, and plasma creatinine （Cr） level. Results Blood gas analysis showed that pH, partial pressure of oxygen in artery （PaO=） and base excess （BE） lowered significantly （all P〈0. 01） in LPS group compared with normal control group, and elevated in low -dose and large dose UT intervention groups compared with LPS group, the differences were statistically significant （P 〈0.01 ） . The plasma endothelin- 1 increased significantly （P,〈0. 01） in LPS group compared with normal control group and intervention groups. Plasma lactate increased significantly in LPS group compared with normal control group （P=0. 001）, decreased significantly in intervention groups compared with LPS group （P〈0. 01）. No significant difference was found between two intervention groups （P〉0. 05）. Plasma Cr and urine NAG level increased in LPS groups, and the difference was significant compared with normal control groups and intervention groups （P 〈 0. 01 ）. Pathohistologic examination revealed normal glomeruli but vacuolar degeneration of tubular epithelial cells, and part of them disrupted and desquamated, and also tubular dilatation. Only mild pathological changes were seen in the intervention groups. There was no obvious difference in morphology between two interventio

关 键 词：蛋白酶抑制剂 内毒素 大鼠 肾功能损害 保护作用 用药剂量 

分 类 号：R96[医药卫生—药理学]