目的:观察平喘宁对寒性哮喘大鼠肺组织中转化生长因子-β1(TGF-β1)、细胞周期蛋白D1(Cyclin D1)和磷酸化细胞外信号调节激酶1、2(p-ERK1/2)m RNA表达的影响。方法:雄性SD大鼠105只,随机分为正常组、模型组、桂龙咳喘宁组、地塞米松组、平喘宁高剂量组、平喘宁中剂量组、平喘宁低剂量组,每组15只。以卵蛋白致敏及寒冷刺激复制大鼠哮喘模型,造模21d后,正常组、模型组每天给予蒸馏水灌服,其它各组给予相应药物灌服,4周后解剖大鼠并取出肺组织。采用免疫组化法测定肺组织中TGF-β1、Cyclin D1的含量,采用RT-PCR检测平喘宁治疗哮喘前后p-ERK1/2 m RNA表达的变化。结果:和正常组比较,模型组发生明显炎性细胞侵润,气道平滑肌增厚;肺组织TGF-β1、Cyclin D1的表达水平上升(P<0.05,P<0.01);p-ERK1/2 m RNA表达水平提高(P<0.05,P<0.01)。和模型组比较,各治疗组肺组织病理改变有不同程度的好转;TGF-β1、Cyclin D1表达下降,p-ERK1/2 m RNA表达水平降低(P<0.05,P<0.01)。结论:平喘宁可通过抑制P-ERK1/2 m RNA表达,调节ERK信号转导通路,抑制TGF-β1、Cyclin D1表达,抑制气道重塑而治疗哮喘。
OBJECTIVE:To study the functional mechanism of Pingchuanning Decoction in treatment of airway remodeling in asthmatic rats.METHODS:Eighty healthy Wistar male rats were randomized into eight groups(n=10 rats each):Normal group,Asthma model group,Dexamethasone group,Guilong Kechuanning group,Xiaoqinglong Decoction group,and Pingchuanning Decoction low-,middle-,and high-dose groups.The rats of all but the Normal group were made into asthma models through intraperitoneal injection and aerosol inhalation of ovalbumin.All treatments were administered at the first stimulation of asthma onset(third week of modeling),and the rats were killed after stimulating asthma attacks for 4 weeks.The general conditions of rats and pathomorphological changes of the lung tissues were observed.The expression of nerve growth factor(NGF) of the lung tissues was measured with immunohistochemical methods,and the content of Clara cell secretory protein(CCSP) mRNA was determined with RT-PCR.RESULTS:Compared with the Normal group,the contents of NGF and CCSP mRNA in the lung tissues of the Model group were significantly changed(P<0.01).Compared with the Model group,the indices of Pingchuanning Decoction and other treatment groups were improved to some extent(P<0.05 or P<0.01).CONCLUSIONS:Pathological changes of airway inflammation and remodeling were present in these rat asthma models.Pingchuanning Decoction had an intervention effect on these experimental models.Its functional mechanism may be related to multiple factors,including alleviation of airway inflammation,relief of bronchial smooth muscle spasm,and inhibition of airway remodeling.
