氧化苦参碱对脓毒症大鼠肺组织中JAK/STAT信号通路的影响

[Effect of oxymatrine on JAK/STAT iteral in rat lung tissue with sepsis].

作者信息

Zhang Minghao, Li Guizhong, Cao Jun

机构信息

Dept of Pathophysiology, Ningxia Med University, Yinchuan 750004, China.

出版信息

Zhongguo Zhong Yao Za Zhi. 2010 Jan;35(1):103-7. doi: 10.4268/cjcmm20100122.

DOI:10.4268/cjcmm20100122

PMID:20349727

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 x kg(-1), vena caudalis bolus), and positive control group (dexamethasone, 10 mg x 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-alpha (TNF-alpha) 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-alpha and IL-6 levels in pulmonary tissue homogenate decreased markedly (TNF-alpha decreased 36%, 26%, 16% and IL-6 decreased 46%, 39%, 24% on CLP + OMT 52, 26 mg x kg(-1) and 13 mg x 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-alpha, IL-6) and antagonize the lung injury in a rat model of sepsis.

摘要

目的

探讨氧化苦参碱（OMT）对脓毒症大鼠肺组织中JAK/STAT信号通路的影响。

方法

将56只雄性SD大鼠随机分为6组：假手术组、模型（CLP）组、CLP + OMT高、中、低剂量组（52、26、13 mg·kg⁻¹，尾静脉推注）和阳性对照组（地塞米松，10 mg·kg⁻¹，尾静脉推注），观察氧化苦参碱对肺湿重与干重比值（W/D）、肺系数的影响，以及肺组织大体变化和光镜下病理变化。采用免疫组化法检测肺组织中JAK2和STAT3活性变化。采用放射免疫法检测肺组织中肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）水平。

结果

OMT可显著降低肺组织中JAK2和STAT3阳性反应及活性（P < 0.05）。肺组织匀浆中TNF-α和IL-6水平明显降低（CLP + OMT 52、26 mg·kg⁻¹和13 mg·kg⁻¹组中TNF-α分别降低36%、26%、16%，IL-6分别降低46%、39%、24%。P < 0.05或P < 0.01）。OMT可降低肺湿重与干重比值及肺系数，改善肺充血、水肿、嗜异性粒细胞浸润及窒息膜形成情况，减轻炎症反应。且结果与阳性对照（CLP + 地塞米松）组相当。