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家兔结核性淋巴结炎模型建立及化痰解凝糊药效作用探讨

Establishment of a rabbit model of tuberculous lymphadenitis and exploration of pharmacological effects of Huatan Jiening paste

  • 摘要: 本文旨在建立家兔结核性淋巴结炎(TBL)模型,考察化痰解凝糊局部外用的药效作用。方法采用淋巴结周边注射完全弗氏佐剂和淋巴结内注射卡介苗,联合诱发淋巴结免疫炎症反应,进而构建家兔TBL模型。模型动物采用淋巴结部位贴敷给药,连续14天,进行体重、腘窝淋巴结血流量、血液白细胞数量和分类、血清炎症因子、淋巴结重量、淋巴结结核分枝杆菌IS6110基因和炎症因子表达、淋巴结组织病理学检查。实验结果显示TBL模型家兔体重明显下降,且伴有腘窝淋巴结显著肿大,淋巴结部位血流灌注显著下降。化痰解凝糊可减缓模型动物体重下降,显著抑制淋巴结肿大并明显增加淋巴结部位血流灌注。化痰解凝糊对模型动物的系统性炎症性改变具有显著的抑制作用,包括显著减少血液白细胞数量,升高淋巴细胞比值并降低中性粒细胞比值,明显降低血清CRP、PCT、TNF-α、IL-1β和IL-6等炎症因子水平。模型组家兔淋巴结组织中CRP、PCT、ICAM-1、SOCS3、TNF-α、IL-1β、IL-6、INF-γ等mRNA表达显著上调,而MIP-1α、IL-10表达显著下调,化痰解凝糊对模型动物淋巴结组织内免疫和炎症因子失衡具有全面的改善作用,对上调的基因具有显著的抑制作用,对于下调的基因也有一定恢复作用。淋巴结组织病理学检查显示以巨噬细胞相关的炎症病变为主,化痰解凝糊对淋巴结组织学病变也具有一定改善作用。研究结果表明化痰解凝糊局部用药对TBL家兔模型具有消肿、抗炎、血流微循环的全面改善作用,对TBL家兔模型淋巴结组织内细胞因子网络也可见显著的调节作用。

     

    Abstract: This study aims to establish a rabbit model of tuberculous lymphadenitis (TBL) and investigate the pharmacological effects of topical application of Huatan Jiening paste (HTJN). Methods about Rabbit TBL model was established by peripheral injection of complete Freund's adjuvant and intralymph node injection of BCG. The body weight, popliteal lymph node blood flow, number and classification of blood leukocytes, serum inflammatory factors, lymph node weight, expression of Mycobacterium tuberculosis IS6110 gene and inflammatory factors in lymph nodes, and lymph node histopathology were examined after 14 days of topical administration. The results showed that the body weight of TBL model rabbits decreased significantly, accompanied by significant swelling of popliteal lymph nodes, and the blood perfusion of lymph nodes decreased significantly. HTJN could improve the weight loss of model animals, significantly inhibit the swelling of lymph nodes and significantly increase the blood perfusion of lymph nodes. HTJN had a significant inhibitory effect on the inflammatory changes of model animals, including significantly reducing the number of blood leukocytes, increasing the lymphocyte ratio and reducing the neutrophil ratio, significantly reducing the levels of serum CRP, PCT, TNF-α, IL-1β, IL-6. The mRNA expressions of CRP, PCT, ICAM-1, SOCS3, TNF-α, IL-1β, IL-6, INF-γ in the lymph node tissues of rabbits were significantly up-regulated, while the expressions of MIP-1α and IL-10 were significantly down regulated. HTJN had a comprehensive improvement effect on the imbalance of immune and inflammatory factors in the lymph node tissues of model animals, a significant inhibitory effect on the up-regulated genes, and a certain recovery effect on the down regulated genes. Histopathological examination of lymph nodes showed that macrophage related inflammatory lesions were the main type, and HTJN also had a certain improvement effect on histological lesions of lymph nodes. This study provides the local application of HTJN has the comprehensive improvement effects of detumescence, anti inflammation and improving blood flow microcirculation in the rabbit model of TBL, and can also significantly regulate the cytokine network.

     

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