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目的:静脉应用蛋白酶抑制剂以了解其对内毒素所致的大鼠肺损伤的保护作用及其机制。方法:雄性Wistar大鼠32只,体重(250~270g),分为对照组(C,n=8)、内毒素组(A,n=8)、大剂量治疗组(U,n=8)及小剂量治疗组(V,n=8),除对照组外,其他组均给予内毒素(5mg/kg),治疗组同时给予内毒素和乌司他丁注射(U组100000u/kg,V组50000u/kg)。2h后测定血清内皮素,进行动脉血气分析,取肺组织观察大体标本形态和光镜下的组织病理形态,测定肺组织血管通透性变化、湿/干质量比值、髓过氧化物酶活性、脂质过氧化产物[丙二醛(malonaldehyde,MDA)和共轭二烯(conjugated-diene,C-diene)]。结果:光镜下可见对照组肺组织学正常,内毒素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,而乌司他丁治疗组上述病理表现明显减轻。肺组织湿/干质量比值和每克肺组织伊文思蓝含量在内毒素组分别为(5.41±0.06)和(27.64±2.48)μg,对照组分别为(4.95±0.08)和(12.99±2.83)μg,组间比较差异有统计学意义;U组为(5.0±0.05)和(19.47±2.09)μg;V组为(4.98±0.06)和(21.44±3.12)μg,明显低于内毒素组,U组和V组间差异无统计学意义。血清内皮素及髓过氧化物水平内毒素组分别为(948.23±103.45)u/g和(152.90±8.41)u/g,高于对照组的(729.38±88.64)u/g和(54.62±15.49)u/g,U组为(633.27±93.27)u/g和(119.40±11.32)u/g,V组为(671.87±105.45)u/g和(129.55±9.57)u/g,则低于内毒素组,U组和V组间差异无统计学意义。肺组织脂质过氧化产物水平内毒素组[(MDA(73.95±4.62)nmol/g;C-diene(10.96±0.81)nmol/g]明显高于对照组[MDA(39.65±6.21)nmol/g;C-diene(3.34±0.51)nmol/g],治疗组[U组:MDA(51.26±5.56)nmol/g,C-diene(7.59±0.84)nmol/g;V组:MDA(59.87±4.62)nmol/g,C-diene(8.79±0.45)nmol/g]则较内毒素组明显降低,MDA水平U组低于V组。结论:乌司他丁明显降低肺组织的炎症反应,减轻肺组织的损害,对内毒素所致大鼠肺损伤具有一定的保护作用。
OBJECTIVE: To study the protective effect of intravenous protease inhibitors on endotoxin-induced lung injury in rats and its mechanism. Methods: Thirty two male Wistar rats weighing 250-270g were divided into control group (C, n = 8), endotoxin group (A, n = 8) and high dose treatment group And low-dose treatment group (V, n = 8). In addition to the control group, the other groups were given endotoxin (5mg / kg), and the treatment group were given endotoxin and ulinastatin injection Group 50000u / kg). Serum endothelin was measured after 2 hours, arterial blood gas analysis was performed, and the morphology of lung tissue and the histopathology under light microscope were observed. The changes of vascular permeability, wet / dry mass ratio, myeloperoxidase activity, Peroxidation products [malonaldehyde (MDA) and conjugated-diene (C-diene)]. Results: Under the light microscope, the lung tissue of the control group was normal, diffuse hemorrhage was found in the pulmonary interstitial of endotoxin group, a large number of granulocytes were aggregated and infiltrated in the alveolar cavity, and diffuse alveolar septum thickening was seen. In the ulinastatin group The pathological manifestations significantly reduced. The lung wet / dry mass ratio and Evans blue content per gram of lung tissue were (5.41 ± 0.06) and (27.64 ± 2.48) μg in the endotoxin group and (4.95 ± 0.08) and (12.99 ± 2.83) μg, the difference between the two groups was statistically significant; U group was (5.0 ± 0.05) and (19.47 ± 2.09) μg; V group was (4.98 ± 0.06) and (21.44 ± 3.12) μg, significantly lower than the endotoxin group, There was no significant difference between U group and V group. Serum levels of endothelin and myeloperoxide were (948.23 ± 103.45) u / g and (152.90 ± 8.41) u / g, respectively, higher than that of the control group (729.38 ± 88.64) u / g and (54.62 ± 15.49 ) in the U group were (633.27 ± 93.27) u / g and (119.40 ± 11.32) u / g in the U group and (671.87 ± 105.45) u / g and (129.55 ± 9.57) u / g in the V group There was no significant difference between endotoxin group, U group and V group. The level of lipid peroxidation in lung tissue of endotoxin group [(MDA (73.95 ± 4.62) nmol / g and C-diene (10.96 ± 0.81) nmol / g] ; C-diene (3.34 ± 0.51) nmol / g] in treatment group [U group: MDA (51.26 ± 5.56 nmol / ) was significantly lower than that in the endotoxin group and the level of MDA in the U group was lower than that in the V group.Conclusion: Ulinastatin can significantly reduce the inflammatory reaction in the lung tissue and reduce the lung Tissue damage, endotoxin-induced lung injury in rats has a protective effect.