氨基胍对博莱霉素致大鼠肺纤维化的干预作用及机制

摘要

Objective To investigate aminoguandine ( AG)′s role in bleomycin ( BLM)-induced pulmonary fibrosis in rats .Methods One hundred and sixteen rats were randomly divided into 5 groups, including normal control, BLM, AG, dexamethasone group, AG+dex-amethasone groups .After administration of BLM intratracheally , AG, dexamethasone were given in each group daily , according to the dosage designed.Rats were killed on the 7th, 14th, 21th, 28th days.The content of NO in the bronchoalveolar lavage fluid (BALF) was meas-ured.The degree of fibrosis was evaluated by pulmonary hydroxyproline assay , the expression of TGF-β1 mRNA in lung tissues by RT-PCR. Results (1)The expressions of NO in BALF in AG, dexamethasone, AG+dexamethasone groups were lower than those in BLM group on the 7th,14th days(P<0.05).The expressions of hydroxyproline in lung tissues were lower than those in BLM group on the 14th, 21th days (P<0.05).(2)The expressions of TGF-β1 mRNA in lung tissues were lower than those in BLM group on the 7th, 14th, 21th days(P<0.05 ) .Conclusions AG attenuates BLM-induced lung fibrosis , and it may be relate to the downregulation of TGF-β1 expression .%目的：探讨氨基胍（ AG）对博莱霉素（ BLM）诱导SD大鼠肺纤维化中的干预作用。方法将116只 SD大鼠随机分成5组：正常对照组、BLM组、AG组、激素组和AG＋激素组。经气道给予BLM或生理盐水后，每天给不同组别相应的药物或生理盐水连续28 d。分别在第7，14，21，28天随机处死各组老鼠5只。处死前，取肺泡灌洗液用硝酸还原酶法测一氧化氮（ NO ）的表达。用碱水解法测肺组织中羟脯氨酸的含量及用 RT-PCR检测肺组织中转化生长因子（ TGF）-β1 mRNA的相对表达量。结果①与BLM组比较，AG组、激素组和AG＋激素组支气管肺泡灌洗液（ BALF）中NO的表达在第7，14天下降（P＜0.05），肺组织羟脯氨酸含量减少（P＜0.05）。②各治疗组肺组织TGF-β1 mRNA的相对表达量和 BLM组比较在7，14，21 d明显增加（ P＜0.05）。结论 AG可以降低BLM诱导的肺纤维化程度，作用机制可能是通过抑制TGF-β1的基因表达。