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对沙利度胺衍生物ZSN-12的抗急性肺损伤作用及机制进行了研究。结果显示ZSN-12(200 mg/kg)明显改善油酸致小鼠急性肺损伤的病理改变;抑制肺泡灌洗液(BALF)中中性粒细胞(PMN)的渗出和NO的大量释放(P<0.01,P<0.05),抑制率分别为48%和33%。ZSN-12(200,100,50 mg/kg)明显抑制二甲苯引起的鼠耳肿胀和角叉菜胶引起的足趾肿胀(P<0.01),并呈剂量依赖,给药3小时的抑制率分别为62%,43%,30%和60%,47%,33%;ZSN-12(10,5,1μmol/L)明显抑制ConA诱导的脾T细胞增殖(P<0.01),抑制率分别为33%,30%,22%。综上所述,沙利度胺衍生物ZSN-12对油酸型急性肺损伤有一定的保护作用,其机制主要与其抗炎作用,抑制中性粒细胞渗出,减少NO释放,抑制T细胞增殖有关。
The anti-acute lung injury of thalidomide derivative ZSN-12 and its mechanism were studied. The results showed that ZSN-12 (200 mg / kg) significantly improved the pathological changes induced by oleic acid in acute lung injury and inhibited the exudation of neutrophil (PMN) and the release of NO in BALF P <0.01, P <0.05), and the inhibition rates were 48% and 33% respectively. ZSN-12 (200,100,50 mg / kg) significantly inhibited xylene-induced ear swelling in mice and carrageenan-induced swelling of the toes (P <0.01) in a dose-dependent manner. The inhibitory rates of ZSN- ZSN-12 (10, 5 and 1μmol / L) significantly inhibited ConA-induced proliferation of splenic T lymphocytes (P <0.01), and the inhibitory rates were 33, 62, 43, 30 and 60% %, 30%, 22%. In conclusion, thalidomide derivative ZSN-12 has some protective effects on oleic acid-induced acute lung injury. Its mechanism is mainly related to its anti-inflammatory effect, inhibition of neutrophil exocytosis, reduction of NO release and inhibition of T cells Proliferation related.