Zhi Qiao-Ming, Yang Li-Tao, Sun Hai-chen
Department of Emergency Medicine, Jinling Hospital, School of Clinical Medicine, Nanjing University, PR China.
Intern Med. 2011;50(18):1879-87. doi: 10.2169/internalmedicine.50.5407. Epub 2011 Sep 15.
To evaluate the possible therapeutic effect of ambroxol on pulmonary fibrosis induced by paraquat.
Adult male Sprague-Dawley rats (n=144, 200-250 g) were divided into four groups (Control, Ambroxol, Paraquat, and Paraquat+Ambroxol group) and sacrificed on day 1, 3, 5, 7, 14 and 28. Several significant oxidant stress markers (MDA, SOD and GSH-PX), MPO activity, cytokines (TNF-α, MCP-1, TGF-β1, MMP-2 and TIMP-1), total inflammatory cell count, hydroxyproline content, collagen I and III mRNA were analyzed.
In Paraquat group, the MDA, MPO activity, hydroxyproline contents, the mRNA expression of TNF-α, MCP-1, TGF-β1, MMP-2, TIMP-1, collagen I, collagen III and the number of total inflammatory cells were up-regulated in lung tissue, but SOD and GSH-PX activity were down-regulated in lung tissue compared with Control group (p<0.05). In paraquat+ambroxol group, the MDA, MPO activity, hydroxyproline content, the mRNA expression of TNF-α, MCP-1, TGF-β1, MMP-2, TIMP-1 collagen I, collagen III and the number of total inflammatory cells were significantly decreased, while the SOD and GSH-PX activities in lung tissue were increased compared with Paraquat group (p<0.05). Histological examination of paraquat-treated rats showed lung injury with interstitial edema and widespread inflammatory cell infiltration in the alveolar space and septum, as well as pulmonary fibrosis. Ambroxol could markedly reduce such damage in lung tissue and prevent pulmonary fibrosis.
The results of this study indicated that ambroxol could reduce lung damage and prevent pulmonary fibrosis induced by paraquat.
评估氨溴索对百草枯诱导的肺纤维化的可能治疗效果。
将成年雄性Sprague-Dawley大鼠（n = 144，体重200 - 250 g）分为四组（对照组、氨溴索组、百草枯组和百草枯 + 氨溴索组），并于第1、3、5、7、14和28天处死。分析了几种重要的氧化应激标志物（丙二醛、超氧化物歧化酶和谷胱甘肽过氧化物酶）、髓过氧化物酶活性、细胞因子（肿瘤坏死因子-α、单核细胞趋化蛋白-1、转化生长因子-β1、基质金属蛋白酶-2和金属蛋白酶组织抑制因子-1）、总炎症细胞计数、羟脯氨酸含量、Ⅰ型和Ⅲ型胶原mRNA。
与对照组相比，百草枯组肺组织中丙二醛、髓过氧化物酶活性、羟脯氨酸含量、肿瘤坏死因子-α、单核细胞趋化蛋白-1、转化生长因子-β1、基质金属蛋白酶-2、金属蛋白酶组织抑制因子-1、Ⅰ型胶原、Ⅲ型胶原的mRNA表达以及总炎症细胞数量均上调，但肺组织中超氧化物歧化酶和谷胱甘肽过氧化物酶活性下调（p < 0.05）。与百草枯组相比，百草枯 + 氨溴索组肺组织中丙二醛、髓过氧化物酶活性、羟脯氨酸含量、肿瘤坏死因子-α、单核细胞趋化蛋白-1、转化生长因子-β1、基质金属蛋白酶-2、金属蛋白酶组织抑制因子-1、Ⅰ型胶原、Ⅲ型胶原的mRNA表达以及总炎症细胞数量均显著降低，而肺组织中超氧化物歧化酶和谷胱甘肽过氧化物酶活性增加（p < 0.05）。对百草枯处理的大鼠进行组织学检查显示，肺组织损伤伴有间质水肿以及肺泡腔和肺泡隔中广泛的炎症细胞浸润，以及肺纤维化。氨溴索可显著减轻肺组织中的此类损伤并预防肺纤维化。
本研究结果表明，氨溴索可减轻百草枯诱导的肺损伤并预防肺纤维化。
