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黄芩苷防止肺纤维化大鼠肺内结缔组织生长因子的上调

贾慧, 陈晓玲, 陈超, 胡玉燕, 郧晓静

河北医科大学 基础医学研究所病理生理学研究室； 药学院药理学研究室，石家庄 050017； 河北工程大学医学院护理系，邯郸 056002

摘要

为探讨黄芩苷(baicalin , Bai)防止肺纤维化的机制，本研究观察了Bai 对肺纤维化大鼠肺内结缔组织生长因子(connective tissue growth factor, CTGF)上调的影响。将雄性Sprague-Dawley (SD)大鼠随机分为4 组：生理盐水(normal saline,NS)+NS 组(气管内滴注NS，随后每天腹腔注射NS 一次)、NS+Bai 组(气管内滴注NS，随后每天腹腔注射Bai 一次)、博莱霉素(bleomycin, BLM)+NS 组(气管内滴注BLM，随后每天腹腔注射NS 一次)和BLM+Bai 组(气管内滴注BLM，随后每天腹腔注射Bai 一次)。Bai 的剂量分别为每天6、12.5 或50 mg/kg。各组于气管内一次性滴注BLM 或NS 后第28 天处死动物，取肺组织样本。采用氯胺-T 法检测肺组织羟脯氨酸含量(反映肺纤维化程度的指标)，用RT-PCR 和免疫组织化学方法检测肺CTGF 的表达。结果显示，BLM+NS 组大鼠肺羟脯氨酸含量、CTGF 蛋白及mRNA 水平均明显高于NS+NS 组大鼠(均P<0.01)，提示BLM 诱导了大鼠的肺纤维化，且纤维化肺内出现CTGF 表达的上调。BLM+Bai 组大鼠连续28 d 每天腹腔注射6、12.5 或50 mg/kg Bai 后，BLM 所致的肺纤维化明显减轻，同时肺CTGF 表达的上调也得到明显抑制。以上结果提示，Bai 可防止肺纤维化大鼠肺内CTGF 表达的上调，这可能是其防止肺纤维化形成的作用机制之一。

关键词： 黄芩苷; 结缔组织生长因子; 纤维化; 肺; 大鼠

分类号：R363

[Baicalin prevents the up-regulation of connective tissue growth factor in fibrotic lungs of rats.] [Ariticle in Chinese]

JIA Hui, CHEN Xiao-Ling, CHEN Chao, HU Yu-Yan, YUN Xiao-Jing

Department of Pathophysiology, Institute of Basic Medical Sciences； Department of Pharmacology, College of Pharmaceutical Science, Hebei Medical University, Shijiazhuang 050017, China； Department of Nursing, Medical College of Hebei University of Engineering, Handan 056002, China

Abstract

To clarify the mechanism underlying the preventive effect of baicalin (Bai) on fibrosis in lung, we investigated the influence of Bai on the up-regulation of connective tissue growth factor (CTGF) in fibrotic lungs. Male Sprague-Dawley (SD) rats were divided into four groups randomly: normal saline (NS)+NS group (a single intratracheal instillation of NS plus i.p. injection of NS), NS+Bai group (intratracheal instillation of NS plus i.p. injection of Bai), bleomycin (BLM)+NS group (intratracheal instillation of BLM plus i.p. injection of NS) and BLM+Bai group (intratracheal instillation of BLM plus i.p. injection of Bai). All the i.p. injections were performed once daily. On day 28 after intratracheal instillation of BLM or NS, the rats were sacrificed for lung tissue sampling. As the index of the severity of pulmonary fibrosis, the content of hydroxyproline in lungs was analyzed by chloramine T method. The expression levels of CTGF mRNA and protein in the lungs were detected by RT-PCR and immunohistochemistry, respectively. The results showed that, compared to the rats in NS+NS group, the rats in BLM+NS group showed increased hydroxyproline content and higher levels of CTGF mRNA and protein expressions (P<0.01), suggesting that BLM had induced fibrosis in lung and up-regulated CTGF expression in the fibrotic lungs. Administration of different dosages of Bai (6, 12.5 and 50 mg/kg per d, for 28 days) into the BLM-treated rats reduced the increased content of hydroxyproline, and ameliorated the up-regulation of CTGF mRNA and protein levels, respectively. These results suggest that Bai could prevent the up-regulation of CTGF expression in fibrotic lungs of rats receiving BLM instillation, which might be one of the mechanisms underlying the preventive effect of Bai on pulmonary fibrosis.

Key words: baicalin; connective tissue growth factor; fibrosis; lung; rats

收稿日期：2010-09-10　　录用日期：2010-11-03

通讯作者：陈晓玲　　E-mail: chen_xiaoling123@126.com

引用本文：

贾慧, 陈晓玲, 陈超, 胡玉燕, 郧晓静. 黄芩苷防止肺纤维化大鼠肺内结缔组织生长因子的上调[J]. 生理学报 2010; 62 (6): 535-540.

JIA Hui, CHEN Xiao-Ling, CHEN Chao, HU Yu-Yan, YUN Xiao-Jing. [Baicalin prevents the up-regulation of connective tissue growth factor in fibrotic lungs of rats.] [Ariticle in Chinese] . Acta Physiol Sin 2010; 62 (6): 535-540 (in Chinese with English abstract).