蛋白酶抑制剂和激素对肺损伤保护作用的比较

目的 探讨并比较蛋白酶抑制剂和激素对内毒素性急性肺损伤的保护作用,为临床药物的选择提供依据.方法 新西兰大白兔32只,随机(随机数字法)分为对照组(C组)、内毒素组(L组)、乌司他丁组(U组)和地塞米松组(D组),每组8只.除C组外,其他组均经耳缘静脉给予内毒素(600μg/kg),U、D组在给予内毒素同时分别静脉注射乌司他丁(100000 U/kg)、地塞米松(5 mg/kg).4h后测定血清肿瘤坏死因子α(TNF-α)及一氧化氮(NO)水平,行动脉血气分析,取肺组织观察大体标本形态和光镜下的组织病理形态,测定肺组织湿/干质量比值(W/D)、髓过氧化物酶(MPO)活性、脂质过氧化产物丙二醛(MDA)及超氧化物歧化酶(SOD)活性.数据采用单因素方差分析(SNK-q检验),以P<0.05为差异有统计学意义.结果 光镜下见C组肺组织学正常,L组肺间质弥漫性出血、肺泡腔内可见大量粒细胞聚集、浸润,并可见弥漫性肺泡间隔增厚,而U,D组上述病理表现明显减轻.U,D组与L组相比较兔肺组织湿/干质量比[(5.02±0.11),(4.93 ±0.13)vs.(5.37±0.29)],MPO[(0.51±0.05),(0.54 ±0.07)vs.(0.82±0.09)],MDA[(0.82±0.05),(0.81±0.04)vs.(0.96±0.05)]以及血清NO水平[(296.2±11.7),(291.7±15.8)vs.(351.8±19.6)]和TNF-α[D组(2.021±0.122)vs.L组(4.999±0.139)]明显降低、SOD活性[(120.3±6.1),(122.6±3.5)vs.(105.1±8.5)]明显增强、动脉血气中pH[(7.30 ±0.23),(7.30±0.17)vs.(7.22±0.45)]和PaO_2[(101.9±6.8),(102.5±4.7)vs.(80.3±3.3)]明显升高,差异有统计学意义(P<0.05);而U组与D组上述指标相比较,差异无统计学意义(P>0.05);U,D组与L组相比较PaCO_2[(37.0±3.3),(37.6±3.0)vs.(34.8±2.3)],差异无统计学意义(P>0.05).结论 乌司他丁对内毒素性急性肺损伤的保护作用与地塞米松相当,在临床上可替代地塞米松以减少其副作用.

Comparison of effects between protease inhibitor and corticosteroid on lung injury

Objective To study and compare the protective effects of pmtease inhibitor and corticosteroid on endotoxin-indueed acute lung injury in order to guide the choice of appropriate drugs. Method Thirty-two New Zealand rabbits were randomly divided(random number) into four groups with 8 rabbits in each, namely normal controls(C) ; lipopolysaecharide(LPS) group(L) ; ulinastatin(UTI) group(U) and dexamcthasone(DEX) group (D) .Except group C, all rabbits were injected with a dose of LPS 600 μg/kg iv. Meanwhile the rabbits in group U,group D received UTI(100 000 μ/kg), DEX(5 mg/kg), respectively. The specimens were collected 4 hours later for detecting the levels of TNF-α and NO in serum, and blood gas analysis, histological manifestations, the lung wet/dry weight ratio, lung tissue MPO and SOD activity, lung tissue MDA. Data were analyzed by ANOVA (SNK- q test), and P < 0.05 was considered as significantly different. Results Compared with group C, the lungs of the rabbits in group L had inflammatory granulocyte infdtration, diffused alveolar septum thickening and hemorrhagic spots were observed in pathological examinations. The histological changes of group U and group D were much lessened than those in group L. As groups U and D were compared with group L, there were significant differences inmany biomarkers including lung wet/dry weight ratio[(5.02±0.11),(4.93±0.13) vs.(5.37 ±0.29)],lung tissue MPO activity[(0.51 ± 0.05),(0.54±0.07) vs.(0.82 ± 0.09)] and MDA[(0.82 ±0.05),(0.81 ±0.04) vs.(0.96±0.05)], NO[(296.2± 11.7),(291.7 ± 15.8) vs.(351.8±19.6)] and TNF-α[group D(2.021 ± 0.122) vs. group L(4.999 ± 0.139)],lung tissue SOD activity[(120.3 ± 6.1),(122.6±3.5) vs.(105.1 ± 8.5)] and blood gas analysis[pH(7.30±0.23),(7.30±0.17) vs.(7.22±0.45) and PaO_2( 101.9 ± 6.8).( 102.5 ± 4.7) vs.(80.3 ± 3.3)] ; but there were no differences of above mentioned biomarkers between group U and D( P > 0.05). And there were no significant differences in PaCO_2 betweeu group U and D and group L[(37.0 ± 3.3),(37.6 ± 3.0) vs.(34.8 ± 2.3)]( P > 0.05). Conclusions The protective effects of ulinastatin on endotoxin-induced acute lung injury is comparable to those of dexamethasone, thus the former may be a clinical substitute for the latter with less side effects.