目的: 探究党参多糖是否通过抑制免疫途径中的相关炎症反应改善急性肺栓塞。方法: 选取60只6月龄健康SD大鼠,雌雄各半,将其随机分为5组:假手术组、模型组、党参多糖高剂量组(200 mg·kg^-1·d^-1)、中剂量组(100 mg·kg^-1·d^-1)、低剂量组(50 mg·kg^-1·d^-1)。采用颈内静脉注射自体血栓建立肺栓塞大鼠模型,通过观察日常行为,并结合血氧饱和度检测、D-二聚体(D-dimer, D-D)水平检测及超敏C反应蛋白(high-sensitivity C-reactive protein, hs-CRP)水平检测,综合判断模型制备是否成功。给予模型动物不同剂量的党参多糖连续灌胃1周后,观察动物日常行为,检测血氧饱和度;酶联免疫吸附试验(ELISA)检测大鼠血清中hs-CRP、同型半胱氨酸(homocysteine, Hcy)、D-二聚体、血栓素(thromboxane A2, TXA2)合成酶、前列环素(prostacyclin, PGI2)合成酶等生化指标;Western blot检测大鼠肺组织D-二聚体及纤溶酶原激活物抑制剂-1(plasminogen activator inhibitor-1, PAI-1)的蛋白表达水平;放射免疫法检测血浆白介素-6(interleukin-6,IL-6)及肿瘤坏死因子-α(tumor necrosis factor-α, TNF-α)水平。结果: 造模后实验大鼠出现呼吸困难、腹式呼吸、鼻翼煽动次数均增加(P＜0.05),心率、血氧饱和度均下降(P＜0.05);与模型组比较,党参多糖各剂量组腹式呼吸、鼻翼煽动均降低(P＜0.05),CPP各剂量组心率、血氧饱和度均升高(P＜0.05);ELISA结果显示,与假手术组比较,模型组血清hs-CRP、Hcy、TXA2合成酶及PGI2合成酶水平增加(P＜0.05),与模型组比,党参多糖各剂量组血清hs-CRP、Hcy、TXA2水平下降(P＜0.05),PGI2水平增加(P＜0.05),并呈现剂量依赖性;Western blot检测结果显示,模型组D-D及PAI-1的蛋白表达较假手术组增加(P＜0.05);与模型组比较,党参多糖各剂量组均下降(P＜0.05);放射免疫法检测结果显示,与假手术组比较,模型组血清IL-6及TNF-α水平增加(P＜0.05);与模型组比较,党参多糖各剂量组血清IL-6及TNF-α水平均下降(P＜0.05)。结论: 党参多糖可通过抗炎、抑制血栓形成,以及调节促炎/抗炎细胞因子网络以抑制过度炎症反应,从多途径发挥对肺栓塞的治疗作用。

Objective: To investigate whether Codonopsis pilosula polysaccharides (CPP) alleviate acute pulmonary embolism (APE) via suppression of inflammation-mediated immune responses. Methods: Sixty 6-month-old healthy SD rats, half male and half female, were randomly divided into five groups: sham operation group, model group, high-dose Codonopsis pilosula polysaccharide group(200 mg·kg^-1·d^-1), medium-dose Codonopsis pilosula polysaccharide group (100 mg·kg^-1·d^-1), low-dose Codonopsis pilosula polysaccharide group (50 mg·kg^-1·d^-1). The rat model of pulmonary embolism was established by internal jugular vein injection of autologous thrombus. The success of model preparation was comprehensively judged by observing daily behavior, combined with blood oxygen saturation detection, D-dimer (D-D) level detection and high-sensitivity C-reactive protein (hs-CRP) level detection. Different doses of Codonopsis pilosula polysaccharide were given to the model animals for 1 week. The daily behavior of the animals was observed and the blood oxygen saturation was detected. The serum levels of hs-CRP, homocysteine (Hcy), D-dimer, thromboxane A2 (TXA2) synthase and prostacyclin (PGI2) synthase were detected by enzyme-linked immunosorbent assay (ELISA). The protein expression levels of D-dimer and plasminogen activator inhibitor-1 (PAI-1) in lung tissue of rats were detected by Western blot. The levels of plasma interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were detected by radioimmunoassay. Results: After modeling, the number of dyspnea, abdominal breathing and alar agitation in the experimental rats were increased (P＜0.05), and the heart rate and blood oxygen saturation were decreased (P＜0.05). Compared with the model group, the abdominal respiration and nasal alar agitation in each dose group of Codonopsis pilosula polysaccharide were decreased (P＜0.05), and the heart rate and blood oxygen saturation in each dose group of Codonopsis pilosula polysaccharide were increased (P＜0.05). ELISA results showed that compared with the sham operation group, the levels of serum hs-CRP, Hcy, TXA2 synthetase and PGI2 synthetase in the model group were increased (P＜0.05). Compared with the model group, the levels of serum hs-CRP, Hcy and TXA2 in each dose group of Codonopsis pilosula polysaccharide were decreased (P＜0.05), and the level of PGI2 was increased (P＜0.05) in a dose-dependent manner. The results of Western blot showed that the protein expression of D-D and PAI-1 in the model group was higher than that in the sham operation group (P＜0.05). Compared with the model group, that in each dose group of Codonopsis pilosula polysaccharide was decreased (P＜0.05). The results of radioimmunoassay showed that the levels of serum IL-6 and TNF-α in the model group were higher than those in the sham operation group (P＜0.05). Compared with the model group, the levels of serum IL-6 and TNF-α in each dose group of Codonopsis pilosula polysaccharide were decreased (P＜0.05). Conclusion: Codonopsis pilosula polysaccharide can inhibit excessive inflammatory response by anti-inflammatory, inhibiting thrombosis, and regulating pro-inflammatory/anti-inflammatory cytokine network, which play a therapeutic role in pulmonary embolism from multiple pathways.