氧化苦参碱对脓毒症大鼠肺组织JAK/STAT信号通路的影响
投稿时间:2009-04-24    责任编辑:  点此下载全文
引用本文:张鸣号,李桂忠,曹军.氧化苦参碱对脓毒症大鼠肺组织JAK/STAT信号通路的影响[J].中国中药杂志,2010,35(1):103.
DOI:10.4268/cjcmm20100122
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作者中文名作者英文名单位中文名单位英文名E-Mail
张鸣号 ZHANG Minghao 宁夏医科大学 病理生理学教研室, 宁夏 银川 750004 Dept of Pathophysiology, Ningxia Med University, Yinchuan 750004, China  
李桂忠 LI Guizhong 宁夏医科大学 病理生理学教研室, 宁夏 银川 750004 Dept of Pathophysiology, Ningxia Med University, Yinchuan 750004, China  
曹军 CAO Jun 宁夏医科大学 病理生理学教研室, 宁夏 银川 750004 Dept of Pathophysiology, Ningxia Med University, Yinchuan 750004, China caojun@nxmc.edu.cn 
基金项目:宁夏回族自治区自然科学基金项目(NZ0534);宁夏医科大学2008年面上项目(XM200816)
中文摘要:目的: 观察氧化苦参碱(oxymatrine,OMT)对脓毒症大鼠肺组织JAK/STAT通路的影响。 方法: 采用大鼠盲肠节扎穿孔法(cecal ligation and puncture,CLP)复制大鼠脓毒症模型,随机将56只清洁级、健康雄性SD大鼠分为假手术组、模型组、 OMT高、中、低(52,26,13 mg·kg-1)剂量组、阳性药地塞米松10 mg·kg-1)对照组。观察OMT对脓毒症大鼠肺组织W/D、肺系数等指标及肺组织病理学改变的影响。采用免疫组化法检测肺组织JAK2及STAT3的活性;放射免疫分析法测定肺组织匀浆中肿瘤坏死因子-α(TNF-α)及白细胞介素-6(IL-6)的含量改变。 结果: 不同剂量的OMT能使肺组织中JAK2及STAT3的阳性反应明显减弱,显著抑制了肺组织JAK2及STAT3的活性(P<0.05);降低肺组织匀浆中TNF-α及IL-6的含量TNF-α:OMT高、中、低剂量组分别降低了36%,26%和16%(P<0.05或P<0.01);IL-6:OMT高、中、低剂量组分别降低了46%,39%和24%(均P<0.01);降低肺组织W/D比值及肺系数(均P<0.05),改善肺组织充血、水肿和中性粒细胞大量浸润及透明膜形成等病变,并且该作用在OMT高、中剂量组与阳性对照组的结果相一致。 结论: OMT能通过抑制JAK-STAT信号通路的活化从而抑制细菌、病毒等对JAK2的激活作用,减少TNF-α,IL-6等促炎因子的表达,进而对脓毒症大鼠肺损伤性病变发挥治疗作用。
中文关键词:氧化苦参碱  脓毒症  肺损伤  细胞因子  JAK/STAT
 
Effect of oxymatrine on JAK/STAT iteral in rat lung tissue with sepsis
Abstract:Objective: To explore the effects of oxymatrine (OMT) on JAK/STAT iteral in rat lung tissue with sepsis. Method: Fifty-six male SD rats were randomly divided into 6 groups: sham operation group, model (CLP) group,CLP+OMT high, middle, low-dose groups (52, 26, 13 mg·kg-1, vena caudalis bolus), and positive control group (dexamethasone, 10 mg·kg-1, vena caudalis bolus) to observe the effects of oxymatrine on the ratio between wet weight of the lung and dry weight of the lung (W/D) and pulmonary coefficient, gross changes and pathological changes examined with lightmicroscope in the pulmonary tissue. Changes in JAK2 and STAT3 activity in the pulmonary tissue were determined by immunohistochemical method. Tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels in pulmonary tissue were determined by radioimmunoassay. Result: OMT could decrease significantly the JAK2 and STAT3 positive reaction and activity in the pulmonary tissue (P<0.05). TNF-α and IL-6 levels in pulmonary tissue homogenate decreased markedly (TNF-α decreased 36%, 26%, 16% and IL-6 decreased 46%, 39%, 24% on CLP+OMT 52 ,26 mg·kg-1 and 13 mg·kg-1 groups. P<0.05 or P<0.01). OMT could decrease the ratio between wet weight of the lung and dry weight of the lung and the pulmonary coefficient, improve the condition of pulmonary hyperemia, edema, infiltrate of heterophil granulocyte and emerge of asphyxial membrane, and alleviate the inflammatory reaction. And the results were equal to those of the positive control (CLP+dexamethasone) group. Conclusion: OMT can inhibit JAK/STAT iteral activity and reduce the expression of proinflammatory factor (TNF-α, IL-6) and antagonize the lung injury in a rat model of sepsis.
keywords:oxymatrine  sepsis  lung injury  cell factor  JAK/STAT
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