目的 探究返魂草Senecio cannabifolius Less.多糖對哮喘大鼠的治療作用及機(jī)制。方法 60只SD大鼠隨機(jī)分為對照組、模型組、地塞米松組和返魂草多糖高、中、低劑量（400、200、100 mg·kg^-1）組，采用10%卵清蛋白（OVA）聯(lián)合氫氧化鋁佐劑建立哮喘模型，對照組、模型組給予等體積蒸餾水，連續(xù)ig給藥14 d。記錄大鼠體質(zhì)量變化情況；蘇木精-伊紅（HE）染色觀察氣管、肺組織病理情況；肺功能儀檢測以0、3.125、6.250、12.500、25.000、50.000 g·L^-1氯化乙酰甲膽堿（Mch）霧化下大鼠的氣道阻力最大值（Max Rrs）；對支氣管肺泡灌洗液（BALF）中炎癥細(xì)胞進(jìn)行分類及計數(shù)； ELISA法檢測大鼠血清白細(xì)胞介素4（IL-4）、γ干擾素（IFN-γ）、免疫球蛋白E（IgE）、C-反應(yīng)蛋白（CRP）、白細(xì)胞介素2（IL-2）、腫瘤壞死因子-α（TNF-α）含量；流式細(xì)胞術(shù)檢測大鼠脾臟輔助性T細(xì)胞1（Th1）/輔助性T細(xì)胞2（Th2）的平衡狀態(tài)；¹²⁵IPCR（qRT-PCR）檢測大鼠肺組織中磷脂酰肌醇3-激酶（PI3K）、蛋白激酶B（Akt）、核因子κB p65（NF-κB p65） mRNA表達(dá)水平； Western blotting法檢測大鼠肺組織PI3K/Akt通路和NF-κB p65活化情況。結(jié)果 與模型組相比，返魂草多糖高劑量組大鼠從實驗第15天體質(zhì)量顯著增加（P＜0.01）；氣管、肺組織病理變化顯著改善；在Mch濃度為0、3.125、12.500、25.000、50.000 g·L^-1時，Max Rrs顯著降低（P＜0.05、0.01）； BALF中總細(xì)胞數(shù)、白細(xì)胞、中性粒細(xì)胞數(shù)和嗜酸性粒細(xì)胞數(shù)均顯著下降（P＜0.05、0.01）；血清IL-4、IFN-γ、CRP、IL-2、TNF-α水平顯著下降（P＜0.01）；脾臟Th1顯著升高（P＜0.01），Th2顯著降低（P＜0.01）；肺組織PI3K、Akt、NF-κB p65 mRNA顯著降低（P＜0.05、0.01），肺組織p-PI3K/PI3K、p-Akt/Akt、p-NF-κB p65/NF-κB p65蛋白顯著降低（P＜0.05、0.01）；且返魂草多糖作用均呈劑量相關(guān)性。結(jié)論 返魂草多糖能緩解哮喘大鼠氣管、肺組織病理損傷，降低血清炎癥因子含量，改善哮喘癥狀，其機(jī)制可能與通過抑制NF-κB磷酸化及其上游的PI3K/Akt信號通路，改善Th1/Th2平衡狀態(tài)相關(guān)。

Objective To investigate the therapeutic effects and the mechanism of action of Senecio cannabifolius polysaccharides in asthmatic rats. Methods 60 SD rats were randomly divided into control group, model group, dexamethasone group, and high, medium and low dosage groups (400, 200 and 100 mg·kg^-1) of Senecio cannabifolius polysaccharides, and the asthma model was established by using 10% ovalbumin (OVA) combined with aluminium hydroxide adjuvant, and equal volume of distilled water was given to the control group and the model group for ig 14 consecutive days. The changes in body mass of rats were recorded; Hematoxylin-eosin (HE) staining was used to observe the histopathology of airways and lungs; The maximum airway resistance (Max Rrs) of rats under nebulization with acetylcholine chloride (Mch) at concentrations of 0, 3.125, 6.250, 12.500, 25.000, and 50.000 g·L^-1 was detected by the pulmonary function instrument; inflammatory cells in bronchoalveolar lavage fluid (BALF) were classified and counted; The contents of interleukin-4 (IL-4), interferon-γ (IFN-γ), immunoglobulin E (IgE), C-reactive protein (CRP), interleukin-2 (IL-2), and tumor necrosis factor-α (TNF-α) in rat serum were detected by ELISA; The balance state of helper T cell 1 (Th1)/helper T cell 2 (Th2) in rat spleen was detected by flow cytometry; The mRNA expression levels of phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), and nuclear factor κB p65 (NF-κB p65) in rat lung tissue were detected by real-time fluorescence quantitative PCR (qRT-PCR); and the activation of PI3K/Akt pathway and NF-κB p65 in rat lung tissue was detected by Western blotting. Results Compared with the model group, the high-dose group of Senecio cannabifolius polysaccharides significantly increased the body weight of rats from the 15th day of the experiment (P < 0.01); the pathological changes of trachea and lung tissues were significantly improved; when the concentration of Mch was 0, 3.125, 12.500, 25.000, and 50.000 g·L^-1, Max Rrs was significantly reduced (P < 0.05, 0.01); the total cell count, white blood cells, neutrophils, and eosinophils in BALF were significantly decreased (P < 0.05, 0.01); the levels of IL-4, IFN-γ, CRP, IL-2, and TNF-α in serum were significantly decreased (P < 0.01); Th1 in the spleen was significantly increased (P < 0.01), and Th2 was significantly decreased (P < 0.01); the mRNA levels of PI3K, Akt, and NF-κB p65 in lung tissue were significantly decreased (P < 0.05, 0.01), and the protein levels of p-PI3K/PI3K, p-Akt/Akt, and p-NF-κB p65/NF-κB p65 in lung tissue were significantly decreased (P < 0.05, 0.01); and the effects of Senecio cannabifolius polysaccharides were dose-dependent. Conclusion Senecio cannabifolius polysaccharides can alleviate the pathological damage of trachea and lung tissues, reduce serum inflammatory factors and improve asthma symptoms in asthmatic rats, and it may play an anti-asthmatic role by inhibiting the phosphorylation of NF-κB and its upstream PI3K/Akt signalling pathway and improving the balance of Th1/Th2 cells.

R285.5

吉林省科技廳發(fā)展計劃項目（20240602036RC）