PPARγ激动剂舒张支气管哮喘大鼠气道平滑肌部分机制探讨  

To research of the parts of the mechanism of PPARγ ligand agonist relaxed smooth muscle of airway in asthmatic rat

作　　者：李文军[1] 黄玲[1] 夏俊杰[1] 熊瑛[2] 王开绿[1] 郑晓凤[1] 刘艳群[1] 蒙琴[1] 高峰[1] 

机构地区：[1]绵阳市第三人民医院呼吸内科,绵阳市621000 [2]泸州医学院附属医院呼吸内科,泸州646000

出　　处：《国际呼吸杂志》2013年第21期1605-1609,共5页International Journal of Respiration

基　　金：四川省卫生厅科研课题（070207）

摘　　要：目的探讨过氧化物酶体增殖物活化受体γ（peroxisome proliferatDr activated receptDry，PPART）激动剂罗格列酮（rosiglita-zone，RSG）舒张大鼠气道平滑肌的部分机制。方法SD大鼠40只，按随机数字表法分为正常对照组（A组）、哮喘组（B组），每组20只，制备各组大鼠离体去上皮气管环。观察RSG对乙酰胆碱（acetycholine，ACh）预收缩气管环的舒张作用，观察前列环素合成酶抑制剂吲哚美辛、胞浆可溶性鸟甘酸环化酶抑制剂亚甲基蓝、β2受体阻断剂普萘洛尔、一氧化氮合酶抑制剂左旋硝基精氨酸甲酯（NG-Nitro—L-arginine Methyl Ester，L—NAME）、大电导钙激活钾通道（Large—conductance calcium—activated potassium channels，BKCa）抑制剂伊比蝎毒素（IberiotDxin，IbTX）对RSG舒张气管环作用的影响。结果吲哚美辛、亚甲基蓝、普萘洛尔分别对三种浓度RSG作用于两组气管环的舒张效应均无阻断作用（P值均〉O．05，n=20），L-NAME对三种浓度RSG所引起B组气管环的舒张效应均有阻断作用（RSG浓度从低到高对B组气管环舒张作用与加L—NAME前比较幻值分别为6．00、4．84、4．47，P值均＜0．01，n=20），而对A组无作用（P值均〉O．05，n=20）。IbTx对三种浓度RSG分别作用于A、B两组气管环的舒张效应均有阻断作用（RSG浓度从低到高对A组气管环舒张作用与加IbTX前比较，其tD值分别为：7．03、9．91、17．1，P值均＜0．01；对B组气管环舒张作用与加IbTX前比较，tD值分别为8．00、6．76、11．7，P值均＜0．01，n=20），并且IbTX对A组的阻断作用大于对B组的阻断作用，差异有统计学意义（RSG浓度由低到高t值分别为-3．604，-4．469，-4．724，P值均＜0．01，n=20）。结论RSG对ACh预收缩的大鼠气管环的舒张作用可能与前列环素、胞浆可溶性鸟苷酸环化酶、β2肾上腺素受体无关，与BKCa、一氧化氮有关。Objective To evaluate a part of the mechanism of the rosiglitazone, an agonist of peroxisome proliferator-activated receptor γ （PPARγ）, diastoling airway smooth muscle in rats. Methods 40 SD rats were randomly divided into control group（group A）, asthma group （group B）, n = 20, isolated rats tracheal rings without epithelium in each group were prepared. To evaluate the relaxing effect on isolated rings in rats from group A and group B, which were precontracted by Acetycholine （ACh）. The effect of Indomethacin which was the Prostacyclin synthesis inhibitors, Methylene blue which was the Cytosolic soluble birds adenosine cyclase inhibitor, Propranolol which was the 13z receptor blocker, L-NAME which was the Nitric oxide synthase inhibitor and IbTX which is the The large conductance calcium-activated potassium channel inhibitor on the relaxation of tracheal rings caused by the RSG were observed. Results Indomethacin, Methylene blue and Propranolol were no effect on the relaxation which was induced by the concentration gradient of RSG to tracheal rings in both groups （all P〉0.05, n = 20）. L-NAME was blocking effect on the relaxation which was induced by the three concentrations of RSG in group B （compare of the relaxation which was induced by the three concentrations of RSG in group B tracheal rings, added in L-NAME before and after, the difference was statistically significant, t~ values were 6.00,4.84,4.47 respectively, all P〈0.01, n = 20. But was no blocking effect on the relaxation in group A. all P〉 0.05, n =20. ） IbTX was blocking effect on the relaxation which was induced by RSG in two groups （compare of the relaxation which was induced by the three concentrations of RSG in group A tracheal rings, added in IbTX before and after,the difference was statistically significant, tD were 7.03,9.91,17.1, respectively, all P〈0.01. That was in group B, tD were 8.00,6.76,11.7, respectively, all P〈0.01, n = 20）, and the blocking effect of IbTX on group A tracheal rings was greater

关 键 词：罗格列酮 哮喘 气道 过氧化物酶体增殖物活化受体Γ 

分 类 号：R562.25[医药卫生—呼吸系统]