血必净干预对慢性阻塞性肺疾病大鼠体内炎症因子的影响

目的：通过观察血必净干预对慢性阻塞性肺疾病（COPD）大鼠体内炎症因子的影响，探讨血必净治疗COPD的机制。方法：36只Wistar雄性大鼠随机分为对照组、COPD模型组（简称模型组）、血必净干预组（简称干预组），每组12只。采用香烟烟雾暴露加气管内滴注脂多糖法建立COPD大鼠模型。造模时间共30天，其中干预组在后15天给予血必净4ml／Kg体重尾静脉注射。分别测定各组肺功能，肺组织病理学变化，血清及肺泡灌洗液中肿瘤坏死因子（TNF-α）、白介素-6（IL-6）、白介素-8（IL-8）浓度。结果：模型组大鼠FEV0．3／FVC[（57．8±5．6）％]和动态肺顺应性（Cydn）[（0．098＋0．006）cmH20·mL^-1·s^-1，lcmH20=0．098kPa]均明显低于对照组[（81．4±3．1）％和（0．195±0．012）cmH20·mL^-1·S^-1]，而干预组大鼠[（67．2±3．2）％和（0．142±0．024）cmH20·mL‘S‘。]则较模型组有显著提高，差异均具有统计学意义（t值分别为-13．940、-15．165、-5．552、-6．927，均P〈0．01）；模型组大鼠平均气道阻力（RI）[（0．802±0．070）mL／cmH20]明显高于对照组[（0．224±0．069）mL／cmH20]，而干预组[（0．475±0．050）mL／cmH20]则较模型组有明显下降，差异均具有统计学意义（t值分别为-22．389、-12．658，均P〈0．01）；模型组大鼠血清和肺泡灌洗液中TNF-α、IL-6、IL-8浓度[（27．8±7．4）pg／mL和（340．0±79．6）pg／mL、（209．9±82．1）pg／mL和（337．3±96．4）pg／mL、（37．7±11．4）pg／mL和（69．6±18．9）pg／mL]均显著高于对照组，差异均具有统计学意义（t值分别为-12．466、-19．648、-11．749、-16．364、12．550、14．834，均P〈0．01），而干预组大鼠[（9．6±5．6）pg／mL和（45．6±22．9）pg／mL、（36．3±17．9）pg／mL和（42．9±20．5）pg／mL、（10．3±5．6）pg／mL和（15．7±8．0）pg／mN．~4较模型组有显著降低，差异均具有统计学意义（t值分别为-9．367、-17．390、-10．106、-14．631、10．475、12．772，均P〈0．01）。结论：COPD大鼠血清及肺泡灌洗液中炎症因子TNF-α、IL-6、IL-8的浓度均显著增高，血必净干预能显著下调上述关键致炎因子的表达，并与其临床症状、肺功能、病理学改变相印证。因此，我们推测：血必净可能通过下调COPD炎症时TNF-α、IL-6、IL-8等关键致炎因子的表达，进一步抑制气道炎症的级联效应来发挥其强大的抗炎作用。

The Effect on Inflammatory Cytokine in Rat with Chronic Obstructive Pulmonary Disease after Xuebijing Dealing

Objective： To explore the mechanism of Xuebijing treatment by observing the effect on inflammatory cytokine in rat with chronic obstructive pulmonary disease （COPD） after Xuebijing dealing. Methods： Tirty-six Wister rats were divided into a control group,a COPD group and a dealing group at random. The COPD rat model was established by intratracheal instillation of lipopolysaccharide （LPS） twice and exposuring to cigarette smoke daily for 30 days, and the dealing group was given Xuebijing injection for dose of 4 mL/Kg weight every day in last 15 days. The spirometry was conducted and the pathological changes were observed after the model was established. The concentration of tumor necrosis factor （TNF-α）, interleukin-6 （IL-6）, interleukin-8 （IL-8） in serum and bronchoalveolar lavage fluid was detected by enzyme-linked immunosorbent assay. Results： Significant decrease of FEV0.3/FVC[（57.8± 5.6） %] and dynamic compliance of lung （Cdyn） [（0.098± 0.006） cm H2O.mL^-1. s^-1] , and increase of airway resistance （RI） [（0.802± 0.070） mL/cmH2O] were found in the COPD group compared with the control group [（81.4±3.1） %, （0.195± 0.012） cmH20, mL^-1. s^-1 （0.224 ± 0.069） mL/cm H20] （t=--13.940, -15.165, -22.389, P〈0.01）. Significant increase of FEV0.3/FVC [（67.2± 3.2） %] and dynamic compliance of lung （Cdyn） [（0.142± 0.024） cm H2O mL. s^-1], and decrease of airway resistance （RI） [（0.475± 0.050） mL/cm H20] were found in the dealing group compared with the COPD group 0=-5.552, -6.927, -12.658, P〈0.01）. The concentration of TNF-α, IL-6, IL-8 [（27.8± 7.4） pg/mL, （340.0± 79.6） pg/mL, （209.9± 82.1） pg/mL, （337.3± 96.4） pg/mL, （37.7± 11.4） pg/mL, （69.6± 18.9） pg/mL]in serum and bronchoalveolar lavage fluid of the COPD rats were found to significantly increase compared with the control rats（t=-- 12.466, -19.648, -11.749, -16.364, 12.550, 14.834, P〈0.01）, while the concentration ofTNF-c~, IL-6, IL-8 [（9.6± 5.6） pg/mL, （45.6± 22.9） pg/mL,（36.3± 17.9） pg/mL, （42.9± 20.5） pg/mL, （10.3± 5.6） pg/mL, （15.7± 8.0）pg/mL] inthe dealing rats were found to singificantly decrease compared with the COPD rats （t=--9.367, -17.390, -10.106, -14.631, 10.475, 12.772, P〈0.01）. Conclusion： The concentration of TNF-α, IL-6, IL-8 in serum and bronchoalveolar lavage fluid of the COPD rats were found to significantly increase, which can significantly decrease by Xuebijing treatment. Those changes confirmed with their clinical symptoms, lung function and pathological changes. So we speculated that Xuebijing may downgrade expression of key proinflammatory cytokines in COPD inflammatory, including TNF-α, IL-6 and IL-8, further inhibit the cascade effect of airway inflammation, by which it played strong anti-inflammatory effects.