不同剂量乌司他丁对脂多糖致新生大鼠急性肺损伤MMP-2表达的影响-东南大学学报医学版

不同剂量乌司他丁对脂多糖致新生大鼠急性肺损伤MMP-2表达的影响

单位：东南大学

分类号：

出版年·卷·期（页码）：2011·30·第五期（737-741）

摘要：

[摘要] 目的探讨不同剂量乌司他丁（ulinastatin，UTI）对脂多糖（LPS）诱导的新生大鼠急性肺损伤MMP-2表达的影响，并分析该变化是否具有剂量依赖性。方法选择40只新生7日龄SD大鼠，随机分为生理盐水对照组、急性肺损伤模型组、乌司他丁小剂量组（2.5万U/kg）、乌司他丁中剂量组（5.0万U/kg）、乌司他丁大剂量组（10.0万U/kg），每组8只。以5mg/kg 脂多糖腹腔注射制作急性肺损伤模型，同时予以乌司他丁腹腔注射进行干预，4h后观察新生大鼠肺组织的病理改变，用免疫组织化学和逆转录-聚合酶链反应（RT-PCR）方法检测肺组织中MMP-2的蛋白和mRNA的表达。结果乌司他丁中、大剂量组的MMP-2水平明显低于急性肺损伤模型组（＜0.05，0.01），乌司他丁小剂量组虽低于急性肺损伤模型组，但差异无统计学意义（ ﹥0.05）。结论乌司他丁对LPS致新生大鼠急性肺损有保护作用，是通过抑制肺组织MMP-2的表达水平实现的，且其抑制作用呈剂量依赖性。

Abstract: Objective To investigate the effect of ulinastatin (UTI) of different dosages on MMP-2 expression in lipopolysaccharide (LPS)-induced acute lung injury (ALI) of neonatal rats and analyze whether the changes having dosage-depend or not. Methods Forty neonatal rats of 7-days were randomly divided into saline control group, acute lung injury group, low（25，000U/kg），middle（50，000U/kg）, and high（100，000U/kg） dosage of UTI groups(n=8). The neonatal rats of the ALI and UTI treated were established by intraperitoneal injection LPS, meanwhile, the neonatal rats of low, middle, and high groups were treated with different dosages UTI. The pathological changes of lung tissues were observed. The expression MMP-2 protein and mRNA in the lung tissues were detected by using immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR). Results The level of MMP-2 mRNA and protein in middle and high dosage of UTI groups were lower than in LPS-induced ALI group ( ＜0.05，0.01); the level in low dosage of UTI group was lower than in LPS-induced ALI group, but there was not significantly different ( ﹥0.05). Conclusions UTI can decrease the levels of MMP-2 in LPS-induced ALI of neonatal rats and has dosage-dependence.

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