二黄汤对哮喘模型大鼠肺组织中TGF-β1及体内IL-33的影响

摘要

Objective To investigate the effect of Erhuang decoction on TGF-β1 expression of lung tiusses and the concentrations of IL-33 in asthmatic rats. Methods Fifty Sprague-Dawley rats were randomly divided into five groups equally:Control group, Asthmatic group, Budesonide aerosol group, High-dose Erhuang decoction group ( 68 g/kg)and Low-dose Erhuang decoction group(17 g/kg). The model of asthma was established by ovalbumin (OVA) sensitizing and challeng-ing. Then Erhuang decoction and budesonide aerosol was used respectively for intervention therapy. Histologic HE staining were used to observe the general pathologic alteration and to analyze the total bronchial wall area (Wat) and the muscle wall area(Wam). The protein expressions of TGF-β1 in the lung tissues were detected by immunohistochemistry. The concentra-tions serum IL-33 and BALF were tested by sandwich ELISA. Results There was significant reduction in the infiltrated inflammatory cells in all drug intervention groups compared with asthma group;The Wat and Wam in asthmatic group was significantly higher in than those in Budesonide aerosol group,High-dose Erhuang decoction group and Low-dose Erhuang decoction group ( Watμm2/μm:54.99±8.82, 52.28±7.61, 58.53±7.63 vs 79.50±5.64, P<0.05;Wamμm2/μm:22.74±2.73, 20.63±1.72, 21.20±4.50 vs 30.16±1.68, P<0.05);Compared with control group, BALF and serum IL-33 concentration were significantly higher in asthmatic group. Compared with asthmatic group, all the indicators were significantly decrease in the treatment groups after drug intervention (P<0.05). Andthere was no significant difference between the treatment groups in all the indicators. TGF-β1 expression in lung tissues in asthmatic group were significantly higher than that in control group (12.60 ± 2.25 vs 1.67 ± 0.17). Compared with asthmatic group, there was significantly reduction of TGF-β1 expression in the Budesonide aerosol group (5.51±2.48), High-dose Erhuang decoction group (5.22±2.52) and Low-dose Erhuang decoction group (6.92 ±2.18) (P<0.05). There were no significant difference between the treatment groups. TGF-β1 expression and se-rum IL-33 concentration in asthmatic rats were positively correlated with Wat and Wam. Conclusion The effects of Er-huang decotion on ameliorating the progression of airway remodeling about asthmatic rats may be partially by regulating TGF-β1 and IL-33.%目的：观察二黄汤对哮喘模型大鼠肺组织中转化生长因子β1(TGF-β1)及体内白介素-33(IL-33)的影响。方法50只SD大鼠随机均分为正常组、哮喘组、布地奈德组、高剂量二黄汤组（含生药量68 g/kg）和低剂量二黄汤组（含生药量17 g/kg）。以卵清白蛋白致敏与激发建立哮喘大鼠模型，随后分别用布地奈德、二黄汤干预治疗。肺组织切片HE染色观察病理变化并检测气道管壁厚度（Wat）及气道平滑肌厚度（Wam），用免疫组化法检测肺组织TGF-β1蛋白的表达，酶联免疫法检测血清及支气管肺泡灌洗液（BALF）中IL-33的含量。结果所有药物干预组较哮喘组炎症细胞浸润明显减轻；布地奈德组、高剂量二黄汤组和低剂量二黄汤组Wat均较哮喘组下降（μm2/μm：54.99±8.82、52.28±7.61、58.53±7.63 vs 79.50±5.64，P＜0.05）；布地奈德组、高剂量二黄汤组和低剂量二黄汤组Wam均较哮喘组下降（μm2/μm：22.74±2.73、20.63±1.72、21.20±4.50 vs 30.16±1.68，P＜0.05）；与正常组比较，哮喘组BALF、血清中IL-33的浓度增高，经药物干预后，布地奈德组、高剂量二黄汤组和低剂量二黄汤组低于哮喘组（P＜0.05），但3干预组间差异无统计学意义；哮喘组TGF-β1高于正常组（IOD：12.60±2.25 vs 1.67±0.17），布地奈德组（5.51±2.48）、高剂量二黄汤组（5.22±2.52）和低剂量二黄汤组（6.92±2.18）均低于哮喘组（P＜0.05），3干预组间差异无统计学意义。哮喘大鼠的气道壁厚度和平滑肌厚度与TGF-β1、IL-33呈正相关。结论二黄汤可在一定程度上干预哮喘大鼠气道重塑，其作用可能是通过调节TGF-β1和IL-33实现的。