RAGE与腹腔注射脂多糖诱导新生大鼠急性肺损伤的相关性研究
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淮安市科技计划项目(HASZ2012014)


Correlation between RAGE and intraperitoneal injection of lipopolysaccharide induced acute lung injury in neonatal rats
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    目的:通过腹腔注射途径建立脂多糖(lipopolysaccharide,LPS)诱导的新生大鼠急性肺损伤(acute lung injury,ALI)模型,探讨其与肺组织晚期糖基化终末产物受体(receptor for advanced glycation end-products,RAGE)的相关性-方法:30只SD新生大鼠随机分为5组,每组6只,根据注射LPS剂量分为0.3-1.0-3.0-9.0 mg/kg组及生理盐水对照组,24 h后观察大鼠的一般情况;ELISA法检测血清及支气管肺泡灌洗液(BALF)中肿瘤坏死因子-α(TNF-α)-可溶性RAGE(sRAGE)含量;Western blot法检测肺组织RAGE蛋白水平;real time-PCR法检测RAGE mRNA表达水平;HE染色下对肺组织进行病理学评估-结果:LPS 9 mg/kg组死亡率高达83.3%,故未计入实验组;其余4组结果显示,TNF-α水平-肺组织RAGE蛋白-mRNA及肺组织损伤评分随梯度剂量的增加而升高,而BALF中sRAGE水平随剂量增加而降低-结论:腹腔注射LPS可以诱导产生新生大鼠的ALI,LPS剂量为3 mg/kg可作为模型最佳诱导剂量;RAGE可作为ALI的敏感指标-

    Abstract:

    Objective:To establish a neonatal rat model of acute lung injury(ALI)induced by intraperitoneal administration of various doses of lipopolysaccharide(LPS)and investigate the role of receptor for advanced glycation end-products(RAGE)in ALI. Methods:Thirty newborn rats were randomly divided into five groups(six in each group)according to the different doses of LPS(0.3,1,3 and 9 mg/kg)and saline. All the rats were sacrificed and observed 24 h later. Levels of tumor necrosis factor alpha(TNF-α)and soluble RAGE(sRAGE)in the plasma and bronchoalveolar lavage fluid(BALF)were detected by enzyme-linked immunosorbant assay(ELISA). RAGE mRNA levels in tissue homogenates were detected by RT-PCR and RAGE protein levels by Western blot. The pathological assessment of lung tissues was performed by HE staining. Results:The LPS 9mg/kg group was excluded due to its high mortality(83.3%). When compared to the control group,the levels of TNF-α,the expression of RAGE protein and RAGE mRNA,and the lung damage scores in the other four groups were increased. All these parameters increased in a dose-dependent manner in the LPS groups,while the levels of sRAGE in BALF decreased. Conclusion:LPS intraperitoneal injection can induce ALI in neonatal rats. LPS dosage of 3 mg/kg may be the optimal dose for ALI model in neonatal rats. RAGE can be used as a sensitive indicator of ALI.

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俞 敏,赵 赛,程怀平,田兆方. RAGE与腹腔注射脂多糖诱导新生大鼠急性肺损伤的相关性研究[J].南京医科大学学报(自然科学版),2014,(8):1051-1055

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  • 收稿日期:2014-01-15
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  • 在线发布日期: 2014-08-03
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