Du Qiang, Gu Xiao-yan, Feng Gan-zhu, Shen Li, Cui Jin, Cai Jian-kang, Huang Mao, Yin Kai-sheng
Department of Respiratory Medicine, Second Affiliated Hospital, Nanjing Medical University, Nanjing, China.
Zhonghua Yi Xue Za Zhi. 2011 Nov 29;91(44):3139-42.
To observe the effects of astragaloside IV on the airway remodeling and the expressions of transforming growth factor (TGF)-β1 and thymic stromal lymphopoietin (TSLP) in a murine model of asthma.
Forty-eight BALB/c mice were randomly divided into 4 groups, i.e. control group, asthma group, astragaloside IV group and budesonide group (n = 12 each). The BALB/c mice sensitized to ovalbumin (OVA) were chronically challenged with aerosolized OVA for 8 weeks while the mice in the astragaloside IV group were intragastrically administered with astragaloside IV (50 mg/kg) daily for 8 consecutive weeks. Pulmonary functions were measured to evaluate the resistance of expiration. And pulmonary histopathological analysis was performed to observe the infiltration of inflammatory cells, the hyperplasia of airway global cells and the deposition of collagen. The levels of interleukin (IL)-4 and IL-13 in bronchoalveolar lavage fluid (BALF) were measured by ELISA (enzyme linked immunosorbent assay). The pulmonary expression of α-SMA (alpha-smooth muscle actin) was evaluated by immunohistochemistry. The mRNA and protein expressions of TGF-β1 and TSLP were measured by real-time PCR (polymerase chain reaction) and Western blot respectively.
The treatment of astragaloside IV or budesonide led to a sharp decrease in airway resistance compared with the asthma group at a concentration of acetylcholine in 30 µg/kg (P < 0.05). The PAS(+) epithelial/bronchial epithelial cells, the area of collagen staining and α-SMA staining area were significantly elevated in the asthma group compared with the control group (all P < 0.01) while those in the astragaloside and budesonide groups were obviously inhibited compared with the asthma group (all P < 0.05). The BALF levels of IL-4 and IL-13 were markedly elevated in the asthma group versus the control group (P < 0.01) while those markedly decreased in the astragaloside and budesonide groups versus the asthma group (all P < 0.05). The relative expressions of TGF-β1 and TSLP mRNA (5.23 ± 1.44, 5.70 ± 1.65) were significantly up-regulated in the asthma group versus the control group (1.02 ± 0.21, 1.02 ± 0.25) (P < 0.01) while those in the astragaloside (2.27 ± 0.65, 2.97 ± 1.03) and budesonide groups (2.10 ± 0.57, 3.32 ± 1.11) were obviously down-regulated versus the asthma group (all P < 0.05). The protein levels of TGF-β1 and TSLP in the asthma group (0.89 ± 0.11, 0.74 ± 0.10) were markedly elevated versus the control (0.39 ± 0.04, 0.44 ± 0.05), the astragaloside (0.51 ± 0.08, 0.59 ± 0.12) and the budesonide groups (0.55 ± 0.08, 0.60 ± 0.08) (all P < 0.05).
Astragaloside IV can suppress the progression of airway inflammation, airway hyperresponsiveness and remodeling in a murine model of asthma. The above effects may be partially due to the inhibited expressions of TGF-β1 and TSLP.
观察黄芪甲苷IV对哮喘小鼠模型气道重塑及转化生长因子（TGF）-β1和胸腺基质淋巴细胞生成素（TSLP）表达的影响。
将48只BALB/c小鼠随机分为4组，即对照组、哮喘组、黄芪甲苷IV组和布地奈德组（每组n = 12）。用卵清蛋白（OVA）致敏的BALB/c小鼠经雾化OVA慢性激发8周，而黄芪甲苷IV组小鼠连续8周每日灌胃给予黄芪甲苷IV（50 mg/kg）。测量肺功能以评估呼气阻力。进行肺组织病理学分析以观察炎症细胞浸润、气道全层细胞增生及胶原沉积情况。采用酶联免疫吸附测定（ELISA）法检测支气管肺泡灌洗液（BALF）中白细胞介素（IL）-4和IL-13水平。通过免疫组织化学法评估肺组织中α-平滑肌肌动蛋白（α-SMA）的表达。分别采用实时聚合酶链反应（PCR）和蛋白质免疫印迹法检测TGF-β1和TSLP的mRNA及蛋白表达。
与哮喘组相比，在乙酰胆碱浓度为30 µg/kg时，黄芪甲苷IV或布地奈德治疗可使气道阻力显著降低（P < 0.05）。与对照组相比，哮喘组过碘酸雪夫反应（PAS）（+）上皮/支气管上皮细胞、胶原染色面积及α-SMA染色面积均显著升高（均P < 0.01），而与哮喘组相比，黄芪甲苷组和布地奈德组上述指标均明显受到抑制（均P < 0.05）。与对照组相比，哮喘组BALF中IL-4和IL-13水平显著升高（P < 0.01），而与哮喘组相比，黄芪甲苷组和布地奈德组上述指标均显著降低（均P < 0.05）。与对照组（1.02 ± 0.21，1.02 ± 0.25）相比，哮喘组TGF-β1和TSLP mRNA的相对表达量（5.23 ± 1.44，5.70 ± 1.65）显著上调（P < 0.01），而与哮喘组相比，黄芪甲苷组（2.27 ± 0.65，2.97 ± 1.03）和布地奈德组（2.10 ± 0.57，3.32 ± 1.11）上述指标均明显下调（均P < 0.05）。与对照组（0.39 ± 0.04，0.44 ± 0.05）、黄芪甲苷组（0.51 ± 0.08，0.59 ± 0.12）和布地奈德组（0.55 ± 0.08，0.60 ± 0.08）相比，哮喘组TGF-β1和TSLP蛋白水平显著升高（均P < 0.05）。
黄芪甲苷IV可抑制哮喘小鼠模型气道炎症、气道高反应性及气道重塑的进展。上述作用可能部分归因于TGF-β1和TSLP表达受到抑制。
