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• 基础研究 • 上一篇    下一篇

人参二醇皂苷对内毒素休克大鼠肺CD14和NF-κB表达的影响

李 璐1,2,刘喜春1,于振香1,3李 扬1,赵 丹1,张 健1,赵雪俭1*   

  1. 1. 吉林大学基础医学院病理生理学研究室,吉林 长春130021;2. 长春中医学院基础医学部预防医学教研室,吉林 长春130021;3.吉林大学第一医院呼吸内科,吉林 长春130021
  • 收稿日期:2004-11-04 修回日期:1900-01-01 出版日期:2005-03-28 发布日期:2005-03-28
  • 通讯作者: 赵雪俭

Effects of Panaxadiol Saponins on expressions of CD14 and NF-κB in lung of endotoxic shock rats

LI Lu1,2, LIU Xi-chun1,YU Zhen-xiang1,3,LI Yang1, ZHAO Dan1, ZHANG Jian1, ZHAO Xue-jian1*   

  1. 1. Department of Pathophysiology, School of Basic Medical Sciences, Jilin University, Changchun 130021, China;2. Department of Preventive Medicine, School of Basic Medical Sciences, Changchun of College TCM, Changchun 130021,China;3. Departmentof Respiratory Medicine, First Hospital, Jilin University, Changchun 130021, China
  • Received:2004-11-04 Revised:1900-01-01 Online:2005-03-28 Published:2005-03-28
  • Contact: ZHAO Xue-jian

摘要: 目的:探讨人参二醇皂苷(PDS)对内毒素休克肺损伤保护作用的分子机制。方法:Wistar大鼠随机分为实验对照组(CTRG)、内毒素(LPS)休克组(LPSG)、人参二醇皂苷组(PDSG)和地塞米松组(DEXG)。以内毒素(4 mg•kg-1)复制内毒素休克模型,平均动脉压降至基础血压的2/3为休克状态。取肺组织光镜下进行形态学观察,提取肺总RNA和蛋白,分别以RT-PCR检测CD14和IκBα mRNA表达,应用Western blotting检测CD14和NF-κB的蛋白表达。 结果:①肺组织的病理学变化, LPSG可见弥漫性间质炎性改变,肺泡壁明显增宽,肺泡腔含气量明显减少,很多肺泡腔内有渗出液。PDSG和DEXG的病变显著轻于LPSG;②肺组织CD14 mRNA和蛋白质表达丰度以LPSG最高, PDSG与DEXG均明显低于LPSG(P<0.05),而与CTRG相近(P>0.05)。 IκBα mRNA表达水平,LPSG明显低于CTRG(P<0.01),PDSG与DEXG明显高于LPSG(P<0.05和P<0.01),而与CTRG相近(P>0.05)。LPSG的NF-κB P65蛋白质表达水平明显高于CTRG, PDSG与DEXG的NF-κB P65蛋白质表达水平也低于LPSG(P<0.05),接近CTRG(P>0.05)。结论:PDS与DEX对内毒素休克肺损伤有类似的保护作用,抑制LPS介导的CD14-NF-κB信号转导通路的过度激活是实现对肺保护作用的重要机制。

关键词: 人参属, 二醇类, 皂苷类, 地塞米松, 抗原, CD14, IκBα, NF-κB

Abstract: Objective To explore the molecular mechanism of protective effects of Panaxadiol Saponins (PDS) on lung tissues of endotoxic shock rats. Methods Wistar rats were randomly divided into control group (CTRG), lipopolysaccharide (LPS) shock group (LPSG), LPS shock+dexamethasone group (DEXG) and LPS shock+PDS group (PDSG), respectively. Endotoxin shock models were duplicated by injection of LPS (4 mg•kg-1). The histological changes of the lung tissues stained with hematoxylin and eosin (HE) among four groups were compared through microscopic examination. Meanwhile, the expressions of CD14 and IκBα mRNA were measured by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and the expressions of CD14 and NF-κB proteins were determined by Western blotting assay. Results ①The histological and pathological changes: in LPSG, there was the effusion of a large amount of lymphocytes, mono-macrophages and neutrophils around the alveolar and vascular walls; incrassated alveolar septums and bronchiole walls were caused by hyperemia ,edema and infiltration of pulmonary interstitial;focal atrophia and formation of pneumatocele could be observed; only small amount of alveolus containing air could be found; however, the lung pathologic changes in DEXG and PDSG were significantly slighter than those in LPSG, and they merely showed slight effusion of inflammatory cells, and the content of air in alveolus was near to that in CTRG. ②The expressions of CD14 mRNA and protein in LPSG were significantly higher than those in CTRG(P<0.05), while those in DEXG and PDSG were close to those in CTRG(P>0.05), significantly lower than those in LPSG(P<0.05). The expression of lung IκBα mRNA in LPSG was significantly lower than those in CTRG(P<0.01), while those in DEXG and PDSG were close to that in CTRG(P>0.05) and higher than that in LPSG(P<0.05 and P<0.01). The expression of NF-κB P65 protein in LPSG was significantly strengthened than that in CTRG(P<0.05), while those in PDSG and DEXG were lower than that in LPSG(P<0.05), close to that in CTRG(P>0.05). Conclusion LPS activates the signaling pathway mediated by LPS receptors, the decreasing of IκBα mRNA expression and the increasing of CD14 and NF-kB expressions are the molecular mechanism for the lung tissue injuries, while the opposite changes in PDSG reveal the molecular mechanism of their protective effects on cells and tissues; PDS has the same effects with DEX to protect against the lung tissue injuries of endotoxic shock in rats.

Key words: panax, glycols, saponins, dexamethasone, antigens, CD14, IκBα, NF-κB

中图分类号: 

  • R-332