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异莲心碱对博莱霉素诱导的小鼠肺纤维化的抑制作用。

Inhibitory effects of isoliensinine on bleomycin-induced pulmonary fibrosis in mice.

作者信息

Xiao Jun-Hua, Zhang Jia-Hua, Chen Hong-Lei, Feng Xiu-Ling, Wang Jia-Ling

机构信息

Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P. R. China.

出版信息

Planta Med. 2005 Mar;71(3):225-30. doi: 10.1055/s-2005-837821.

DOI:10.1055/s-2005-837821
PMID:15770542
Abstract

The effects of isoliensinine (IL), a bisbenzylisoquinoline alkaloid extracted from the Chinese traditional medicine seed embryo of Nelumbo nucifera Gaertn., on bleomycin (BLM)-induced pulmonary fibrosis in mice were investigated. Seventy-two male Kungming mice were divided randomly into eight groups as BLM-IL10, BLM-IL20, BLM-IL40, BLM-Sal, Sal-IL10, Sal-IL20, Sal-IL40 and Sal-Sal groups. BLM (0.1 mg in 0.05 ml saline per animal, once) or saline (0.05 ml per animal, once) was applied intratracheally, and IL (10, 20, 40 mg/kg) or saline was administered orally 3 times per day in the appropriate groups. Animals were sacrificed 14 days after intratracheal treatment. Lung tissue and serum superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels, tumor necrosis factor alpha (TNF-alpha) and transforming growth factor beta 1 (TGF-beta (1)) were determined by biochemical measurements and immunohistochemistry. BLM treatment resulted in a significant increase of the hydroxyproline content and an obvious lung histological injury as compared to the Sal-Sal group. Administration of IL remarkably suppressed the increase in hydroxyproline content and abated the lung histological injury induced by BLM. There was a decrease in SOD activity and an increase in MDA level in lung tissue and serum in the BLM-Sal group (p < 0.01 , p < 0.01, vs. Sal-Sal group, respectively). And IL could obviously enhance the SOD activity and decrease the MDA level in a concentration-dependent manner. Moreover, IL also significantly inhibited the overexpression of TNF-alpha and TGF-beta (1) induced by BLM. These results indicated that IL possessed a significant inhibitory effect on BLM-induced pulmonary fibrosis, probably due to its antioxidant and/or anti-inflammatory activities and inhibitory overexpressing TNF-alpha and TGF-beta (1) induced by BLM.

摘要

研究了从中国传统中药莲子种子胚中提取的双苄基异喹啉生物碱异莲心碱(IL)对博来霉素(BLM)诱导的小鼠肺纤维化的影响。将72只雄性昆明小鼠随机分为8组,即BLM-IL10、BLM-IL20、BLM-IL40、BLM-Sal、Sal-IL10、Sal-IL20、Sal-IL40和Sal-Sal组。经气管内给予BLM(每只动物0.1mg溶于0.05ml盐水中,一次)或盐水(每只动物0.05ml,一次),相应组每天口服IL(10、20、40mg/kg)或盐水3次。气管内治疗14天后处死动物。通过生化测定和免疫组织化学测定肺组织和血清中超氧化物歧化酶(SOD)活性、丙二醛(MDA)水平、肿瘤坏死因子α(TNF-α)和转化生长因子β1(TGF-β(1))。与Sal-Sal组相比,BLM治疗导致羟脯氨酸含量显著增加和明显的肺组织学损伤。给予IL可显著抑制羟脯氨酸含量的增加,并减轻BLM诱导的肺组织学损伤。BLM-Sal组肺组织和血清中SOD活性降低,MDA水平升高(分别与Sal-Sal组相比,p < 0.01,p < 0.01)。IL可明显增强SOD活性,并以浓度依赖方式降低MDA水平。此外,IL还显著抑制BLM诱导的TNF-α和TGF-β(1)的过度表达。这些结果表明,IL对BLM诱导的肺纤维化具有显著的抑制作用,可能是由于其抗氧化和/或抗炎活性以及抑制BLM诱导的TNF-α和TGF-β(1)过度表达。

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