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王启瑞,唐靖,孙学刚,石彩霞,吕志平,刘亚伟,范钦,刁建新.大承气汤对内毒素血症小鼠肺与大肠TLR4及TNF-α表达的影响[J].,2011,31(2):244-248
大承气汤对内毒素血症小鼠肺与大肠TLR4及TNF-α表达的影响
Effect of Dachengqi Decoction on Expressions of TLR4 and TNF-α in the Lung and the Large Intestine of Mice with Endotoxemia
  
DOI:
中文关键词:  大承气汤  肺与大肠相表里  toll样受体4  肿瘤坏死因子-α
英文关键词:Dachengqi Decoction  exterior-interior relation between Fei and Dachang  toll-like receptor 4  tumor necrosis factor-α
基金项目:国家973计划资助项目(2009CB522706);国家自然科学基金资助项目(No.30572435)
Author NameAffiliation
WANG Qi-rui 南方医科大学中医药学院分子生物学实验室 
唐靖 南方医科大学省部共建重大疾病的转录组与蛋白质组学教育部重点实验室 
SUN Xue-gang 南方医科大学中医药学院分子生物学实验室 
石彩霞 南方医科大学中医药学院分子生物学实验室 
吕志平 南方医科大学中医药学院分子生物学实验室 
刘亚伟 南方医科大学省部共建重大疾病的转录组与蛋白质组学教育部重点实验室 
FAN Qin 南方医科大学中医药学院分子生物学实验室 
刁建新 南方医科大学中医药学院分子生物学实验室 
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中文摘要:
      目的研究大承气汤(Dachengqi Decoction,DCQD)对内毒素血症小鼠肺、大肠关键信号分子的作用,探讨肺与大肠相表里的关系。方法应用脂多糖(lipopolysaccharide,LPS)10mg/kg腹腔注射BALB/C小鼠制作内毒素血症模型。32只小鼠随机分为4组,分别为对照组、DCQD组、模型组和LPS加DCQD组,每组8只。对照组给予生理盐水灌胃及腹腔注射;模型组给予生理盐水灌胃及LPS腹腔注射;DCQD组给予DCQD灌胃及生理盐水腹腔注射;LPS加DCQD给予DCQD灌胃及LPS腹腔注射。应用倒置显微镜观察肺、大肠组织HE染色切片的组织学变化;应用LiquiChip芯片检测肺、大肠组织肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)的表达;应用RT-PCR和Western blot研究toll样受体4(toll-like receptor4,TLR4)的基因转录与蛋白表达,分析TNF-α和TLR4在肺与大肠组织的相关性。结果与对照组比较,模型组肺与大肠TNF-α表达、TLR4蛋白表达及基因转录水平均增高(P<0.01);LPS加DCQD组肺与大肠TNF-α表达、TLR4蛋白表达及基因转录水平较模型组均降低(P<0.01,P<0.05),但较DCQD组仍显著增高(P<0.01,P<0.05)。经相关分析,肺与大肠组织在TNF-α表达水平(r=0.973,P<0.01)、TLR4蛋白表达水平(r=0.906,P<0.01)及基因转录水平(r=0.880,P<0.01)之间存在正相关关系。结论大承气汤减轻内毒素血症引起的肺与大肠组织炎症,可能与大承气汤降低TNF-α表达、TLR4蛋白表达及基因转录水平有关;肺与大肠组织在TNF-α表达水平、TLR4蛋白表达及基因转录水平之间存在正相关关系,提示肺与大肠存在表里关系。
英文摘要:
      Objective To investigate the effect of Dachengqi Decoction (DCQD) on the key signaling molecules in lung and large intestine of mice with endotoxemia for exploring the exterior-interior relation between Fei and Dachang. Methods A total of 32 BALB/c mice were randomly and equally allocated into four groups:mice in Group C and D were made into endotoxemia model by intraperitoneal injection of 10 mg/kg lipopolysaccharide (LPS); while those in Group A and B were not modeled but given intraperitoneal injection of saline instead. Thirty min after then,saline to Group A and C,and DCQD to Group B and D were given by gastric infusion,and mice were sacrificed 6 h later. Their tissues of lung and large intestine were taken for observing pathological changes by inverted microscopy with HE staining; detecting expressions of tumor necrosis factor-α (TNF-α) by LiquiChip system; determining gene transcription and protein expression of toll-like receptor 4 (TLR4) using reverse transcription-polymerase chain reaction (RT-PCR) and Western blot,and the correlation of TNF-α and TLR4 levels in the lung and the large intestine tissue was analyzed. Results Compared with Group C,hemorrhage,pathologic toxemic features,including pulmonary edema and inflammatory cell infiltration as well as intestinal wall congestion and neutrophil infiltration,were significantly alleviated in Group D. Levels of TNF-α expression,TLR4 protein expression and gene transcription raised significantly in the modeled mice (P<0.01),but comparison between the two modeled groups showed that the three parameters were lower in Group D than in Group C (P<0.01 or P<0.05) respectively. Correlation analysis showed that the levels of TNF-α expression,TLR4 protein expression and gene transcription in pulmonary tissues were positively correlated with those in large intestinal tissues respectively (r=0.973,P<0.01,r=0.906,P<0.01,and r=0.880,P<0.01). ConclusionsThe effects of DCQD in alleviating pulmonary and large intestinal inflammation induced by endotoxemia might be correlated to its reduction on levels of TNF-α expression,TLR4 protein expression and gene transcription. Levels of the three parameters in the lung are correlated with the corresponding levels in the large intestine,which suggested the existence of exterior-interior relation between Fei and Dachang.
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