摘要
目的 研究糖皮质激素、香菇多糖（lentinan，LNT）对哮喘气道重塑大鼠肺组织c-Jun氨基末端激酶（JNK）表达的影响。方法 SD大鼠随机分为正常对照组、哮喘组、布地奈德（BUD）组、地塞米松（DXM）组、LNT组，以卵白蛋白致敏和激发复制哮喘气道重塑模型，干预组分别于每次雾化激发前以BUD雾化或DXM、LNT腹腔注射干预，正常对照组以生理盐水代替卵清白蛋白致敏和激发。留取支气管肺泡灌洗液（BALF）进行细胞分类计数。采用图像分析技术测定支气管壁厚度（Wat）和平滑肌厚度（Wam），免疫组化（IHC）检测肺内磷酸化JNK（p-JNK）蛋白表达，WESTERN BLOT检测肺匀浆p-JNK表达，直线相关分析肺组织p-JNK蛋白平均吸光度（Am）与BALF中嗜酸性粒细胞百分比（EOS%）的相关性以及Wat、Wam与p-JNK蛋白的相关性。 结果 哮喘组BALF中EOS%显著高于正常对照组（P＜0.01），各干预组EOS%均显著低于哮喘组（均P＜0.01），但仍高于正常对照组（P＜0.05或P＜0.01）；哮喘组气道壁厚度较正常对照组显著增加，各干预组可抑制气道壁增厚；BUD、DXM组Wam比较，无显著性差异（P＞0.05），二者均低于LNT组（均P＜0.01）；BUD、LNT组Wat比较无显著性差异（P＞0.05），但均比DXM组高（P＜0.05或P＜0.01）；IHC显示p-JNK蛋白主要表达于支气管上皮细胞、平滑肌细胞及散在炎性细胞的胞浆和胞核；IHC、WESTERN BLOT检测均显示哮喘组肺组织p-JNK蛋白表达增高；BUD、DXM、LNT均可抑制JNK磷酸化；BUD、DXM组p-JNK表达均较LNT组低（均P＜0.01）；肺组织p-JNK Am与BALF中EOS%呈显著正相关（P＜0.01），Wat、Wam与p-JNK Am均呈显著正相关（均P＜0.01）。结论 BUD、DXM、LNT有减轻哮喘气道EOS炎症，抑制哮喘气道重塑的作用，其机制可能与其下调JNK表达有关；LNT抑制气道重塑的作用较糖皮质激素弱。
Abstract
OBJECTIVE To study the effects of glucocorticoids and lentinan （LNT） on the expression of c-Jun NH2-terminal kinase （JNK） in the lung tissues of rats with asthmatic airway remodeling. METHODS Sixty 4-6 weeks old male SD rats were randomly divided into 5 groups with 12 rats in each group： control， asthma， budesonide （BUD）， dexamethasone （DXM） and LNT groups. Asthmatic airway remodeling models were prepared by intra-peritoneal injection of ovalbumin （OVA） on day 1 and 8 and inhalation of OVA every other day for 12 weeks since day 15. Animals in BUD， DXM and LNT group were treated with inhalation of BUD， intra-peritoneal injection of DXM or LNT 30 min before OVA inhalation， respectively； and animals in control group received normal saline instead of OVA. Total brochial wall thickness （Wat） and airway smooth muscle thickness （Wam） were measured by image analysis system. Protein expression of phospho-JNK （p-JNK） in the lung tissue was detected by immunohistochemistry technique. Lung tissue extracts were analyzed for phosphorylation of JNK by WESTERN BLOT. Linear correlation analysis was used to investigate the correlations between p-JNK protein （Am） and EOS% in BALF， Wat and p-JNK protein （Am）， Wam and p-JNK protein （Am）. RESULTS The Wat and Wam in asthma group were significantly higher than those in control group， and the thickness of airway wall in the intervention groups became significantly lower. There was no significant difference in term of Wam between of BUD and DXM group （P＞0.05）. The Wams of the two groups were both lower than that of LNT group （both P＜0.01）. There was no significant difference in term of Wat between BUD and LNT group （P＞0.05）. Wats in those two groups were both higher than that in DXM group （P＜0.05 or P＜0.01）. Mean absorbance values （by immunohistochemistry and Western blot） of p-JNK increased in asthma group， however it decreased in the 3 intervention groups. The expression of p-JNK in BUD and DXM group was both lower than that in LNT group （P＜0.01）. Strong positive correlations were found between p-JNK protein （Am） and EOS% in BALF （P＜0.01）. Strong positive correlations were found between Wat or Wam and p-JNK （Am） （P＜0.01）. CONCLUSION BUD， DXM and LNT can relieve eosinophilic airway inflammation and inhibit airway remodeling in asthmatic rats. The mechanism might be the down-regulation of JNK expression. The inhibitory effect of LNT on asthmatic airway remodeling is not as strong as that of glucocorticoids.
关键词
糖皮质激素 /
香菇多糖 /
哮喘 /
气道重塑 /
JNK丝裂原活化蛋白激酶类
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Key words
glucocorticoids /
lentinan /
asthma /
airway remodeling /
JNK mitogen-activated protein kinases
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林立 李昌崇 张维溪 苏苗赏 叶乐平 项蔷薇 张海邻.
糖皮质激素、香菇多糖对哮喘气道重塑大鼠肺组织c-Jun氨基末端激酶表达的影响[J]. 中国药学杂志, 2011, 46(14): 1092-1096
LIN Li;LI Chng-chong;ZHNG Wei-xi;SU Mio-shng;YE Le-ping;XING Qing-wei;ZHNG Hi-lin.
Effects of Glucocorticoids and Lentinan on the Expression of c-Jun NH2-Terminal Kinase in Lung Tissues of Rats with Asthmatic Airway Remodeling[J]. Chinese Pharmaceutical Journal, 2011, 46(14): 1092-1096
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