川芎嗪对咳嗽变异性哮喘大鼠气道平滑肌组织转化生长因子通路相关蛋白表达的影响  

Effects of ligustrazine on transforming growth factor-βfamily proteins expression in airway smooth muscle tissue in rats with cough variant asthma

作　　者：孙洮玉[1] 任军华[2] 杨斌[2] SUN Tao-yu;REN Jun-hua;YANG Bin(Department of Paediatrics,Dong Zhimen Hospital,Beijing University of Traditional Chinese Medicine,Beijing 100700,China;Department of Pathology,Xiyuan Hospital,Chinese Academy of Traditional Chinese Medicine,Beijing 100091,China)

机构地区：[1]北京中医药大学东直门医院儿科,北京100700 [2]中国中医科学院西苑医院病理科,北京100091

出　　处：《中国临床药理学杂志》2021年第23期3266-3268,3278,共4页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金资助项目(81704120);北京市自然基金面上基金资助项目(7212179);北京中医药大学东直门医院青苗人才培养计划基金资助项目(2018年度)。

摘　　要：目的探讨川芎嗪对咳嗽变异性哮喘大鼠气道平滑肌组织的作用和转化生长因子-β(TGF-β)、蛋白激酶B(Akt)、细胞外调节蛋白激酶(ERK1/2)蛋白表达的影响。方法肌内注射卵蛋白联合腹腔注射氢氧化铝法建立咳嗽变异性哮喘(CVA)大鼠模型。将建模成功后的大鼠随机分为3组:模型组、实验组和阳性药组,各10只;另外选取10只大鼠为正常组。建模3 d后,实验组大鼠灌胃川芎嗪1.05 mg·kg^(-1),阳性药组灌胃孟鲁司特钠32.5 mg·kg^(-1)。模型组与正常组灌胃等量生理盐水,1次/天,连续干预4周。Masson特殊染色测量管壁厚度、气道平滑肌面积和纤维沉积率;免疫组化法检测气道平滑肌组织TGF-β、蛋白激酶B(Akt)与细胞外调节蛋白激酶(ERK1/2)的表达(平均光密度值)。结果正常组、模型组、实验组和阳性药组的标准化管壁厚度分别为(12.53±2.56),(21.13±3.95),(16.21±3.07)和(17.97±3.71)μm;这4组的平滑肌面积分别为(10.23±1.55),(28.71±3.66),(18.54±2.84)和(17.87±2.93)μm;这4组的胶原沉积率分别为(0.21±0.06)%,(0.62±0.18)%,(0.38±0.11)%和(0.44±0.16)%;这4组的TGF-β表达分别为27.37±3.75,48.41±6.23,34.58±4.12和36.79±4.49;这4组的Akt表达分别为18.45±2.83,39.51±4.48,27.35±2.94和30.04±3.52;这4组的ERK表达分别为21.45±3.65,38.69±4.81,29.02±2.59和32.27±4.07。模型组与正常组相比,上述指标的差异有统计学意义(均P<0.05);实验组和阳性药组与模型组相比,上述指标的差异均有统计学意义(均P<0.05)。结论川芎嗪可减轻CVA大鼠气道平滑肌增生肥大和纤维沉积,其机制可能与调节TGF-β、ERK和Akt信号通路有关。Objective To explore the effect of ligustrazine on airway smooth muscle tissue and the expression of transforming growth factor-β(TGF-β),protein kinase B(Akt)and extracellular regulated protein kinases(ERK1/2)in rats with cough variant asthma(CVA).Methods Rats model with cough variant asthma were established by intramuscular injection of ovalbumin combined with intraperitoneal injection o aluminum hydroxide.Successful SD rats model were randomized into 3groups:model group,experimental group,positive drugs group,with 10in each;another 10 rats were selected as the normal group.The experimental group was received 1.05 mg·kg^(-1)ligustrazine,positive drugs group received montelukast 32.5 mg·kg^(-1)montelukast;normal group and the model group were given oral administration of distilled water,respectively.All these rats were intervened once daily,and the intervention lasted for4 weeks.Masson staining was used to measure the thickness and area of airway smooth muscle,and the fiber deposition rate.The expression(mean optical density)of TGF-β,Akt and ERK in airway smooth muscle tissue was detected by immunohistochemistry.Results The thickness of standardized tube wall of normal group,model group,experimental group and positive drugs group were(12.53±2.56),(21.13±3.95),(16.21±3.07),(17.97±3.71)μm,respectively;the smooth muscle area in the 4 groups were(10.23±1.55),(28.71±3.66),(18.54±2.84),(17.87±2.93)μm;,respectively;the collagen deposition rate in the 4 groups were(0.21±0.06)%,(0.62±0.18)%,(0.38±0.11)%,(0.44±0.16)%,respectively;the expression of TGF-βin the 4 groups were27.37±3.75,48.41±6.23,34.58±4.12,36.79±4.49,respectively;the expression of Akt in the 4 groups were18.45±2.83,39.51±4.48,27.35±2.94,30.04±3.52,respectively;the expression of ERK1/2 in the 4 groups were 21.45±3.65,38.69±4.81,29.02±2.59,32.27±4.07,respectively.Compared between the model group and the normal group,the differences of the factors were statistically significant(all P<0.05);compared between the experimental group,

关 键 词：川芎嗪 咳嗽变异性哮喘 气道平滑肌 转化生长因子β 蛋白激酶B 细胞外调节蛋白激酶 

分 类 号：R28[医药卫生—中药学]