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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。
Objective: To observe the effect of oxymatrine (OMT) on JAK / STAT pathway in lung tissue of septic rats. Methods: Fifty-six male Sprague Dawley rats were randomly divided into sham operation group, model group, high OMT, Medium and low (52,26,13 mg.kg-1) dose group, the positive drug dexamethasone 10 mg.kg-1) control group. To observe the effect of OMT on W / D, pulmonary coefficient and lung pathological changes of lung tissue in septic rats. Immunohistochemistry was used to detect the activity of JAK2 and STAT3 in lung tissue. Radioimmunoassay was used to determine the content of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in lung homogenate. Results: Different dosages of OMT could significantly decrease the positive reaction of JAK2 and STAT3 in lung tissue, significantly inhibited the activity of JAK2 and STAT3 in lung tissue (P <0.05), and decreased the levels of TNF-α and IL-6 in lung homogenate (P <0.05 or P <0.01). The levels of TNF-α in OMT high, medium and low dose groups decreased by 36%, 26% and 16% %, 39%, and 24% respectively (all P <0.01). The W / D ratio and pulmonary coefficient of lung tissue were decreased (all P <0.05), and the pathological changes such as hyperemia, edema and neutrophil infiltration, , And this effect was consistent with the results of the OMT high and medium dose groups and the positive control group. CONCLUSION: OMT can inhibit the activation of JAK2 by inhibiting the activation of JAK-STAT signaling pathway and decrease the expression of proinflammatory cytokines such as TNF-α and IL-6, and further inhibit lung injury in septic rats Lesions play a therapeutic role.