目的:探讨L-精氨酸对大鼠急性肺损伤的影响及机理.方法:采用尾静脉注射脂多糖(lipopolysaccharide,LPS)制备大鼠急性肺损伤模型.将45只大鼠随机分为三组:生理盐水对照组(NS组)、急性肺损伤模型组(LPS组)和L-精氨酸预处理组(L-Arg组)(n=15),再各分为2、6、24 h三个时间点.LPS组尾静脉注射LPS(6 mg/kg)制备急性肺损伤模型,L-Arg组在造模前0.5 h腹腔注射L-Arg 500 mg/kg.测定各组大鼠不同时间点的动脉血气分析,肺组织湿/干重(W/D)比,肺组织HE病理切片,ELISA法测定血清TNF-α,硝酸还原酶法测定血清NO,Real Time-PCR法测定肺组织iNOSmRNA.结果:LPS组动脉血氧降低、W/D增高、血清TNF-α及NO增高、肺组织iNOSmRNA增高,且与对照组比较有显著差异(P<0.05),肺组织HE病理切片有肺损伤改变.L-Arg组肺损伤有改善,上述检测指标与LPS组有显著差异(P<0.05).结论:L-精氨酸预处理对LPS致大鼠急性肺损伤有保护作用.%Objective: To observe the effects and the mechanisms of L-Arginine protects against acute lung injury induced by lipopolysaccharide (LPS).Methods: A total of 45 adult male Wistar rats were randomly divided into three groups as follows: control group (NS group), model group (LPS group) and L-Arginine pretreatment group (L-Arg group). LPS (6 mg/kg) was infused by tail vein to reproduce ALI in LPS group and L-Arg group. L-Arginine (500 mg/kg) was intraperitoneally injected 0.5 h before LPS in L-Arg group, whereas NS group and LPS group were given equivalent volume normal saline. Five rats in each group were killed at 2, 6 and 24 h, meanwhile lung tissue, arterial blood and serum were collected. The PaO2 and W/D were determined at different point of time; serum were collected to determine TNF-α by ELISA, and real time PCR was used to detect the mRNA of iNOS. hTe content of NO was determined by nitrate reductase method. hTe pathology changes of lung tissue were observed under light microscope.Results: Rats in the LPS group had sustained hypoxemia, and had a signiifcant increase in W/D, in the concentration of NO and TNF-α, as well as in the pulmonary expression of iNOSmRNA (P<0.05). Under light microscope, interstitial tissue of the lung showed exudation, edema,a great quantity of inlfammatory cells accumulation and red blood corpuscle exosmose. Compared with the LPS group, those items in the L-Arg group had a significant improvement (P<0.05), and the pathology of lung tissue was ameliorated at all time than that in LPS group.Conclusion: Pretreatment of L- Arginine could alleviate the inlfammatory reaction and protect acute lung injury tissues induced by LPS.
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