粉防己碱的抗炎作用与炎症白细胞cAMP的关系  

Relationship between effect of tetrandrine on pleurisy and cAMP of inflammatory neutrophiles

作　　者：张乐之[1] 何华美[1] 李新芳[2] 吕金胜[3] 黄钺华[1] 

机构地区：[1]第三军医大学药理学教研室,重庆400038 [2]白求恩国际和平医院药剂科,石家庄050082 [3]第三军医大学大坪医院药剂科药理室,重庆400042

出　　处：《中国药理学通报》2003年第7期791-796,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助课题No38970 90 6

摘　　要：目的　研究粉防己碱 (tetrandrine,Tet)的抗炎作用与炎症白细胞cAMP的关系。方法　在大鼠胸膜腔内注射角叉菜胶 (1 0mg·kg- 1 )复制胸膜炎 ,并于致炎前 30min腹腔注射Tet。用常规方法测量胸膜腔渗出液量 ,用试管稀释法计数渗出液中白细胞数 ,用放射免疫分析法、间接法、酶放射化学分析法和荧光比色法 ,分别测定炎症白细胞cAMP浓度、腺苷酸环化酶 (AC)、磷酸二酯酶 (PDE)活性及胞质内游离钙浓度 ([Ca2 + ] i) ;体外观察细胞外钙对Tet调节炎症白细胞PDE活性的作用。结果　Tet(1 0～ 80mg·kg- 1 )腹腔注射 ,剂量依赖地降低胸膜腔渗出液量和白细胞游出数 ,同时增加白细胞cAMP浓度 ;Tet亦剂量依赖地降低炎症白细胞PDE活性及 [Ca2 + ] i,但对白细胞AC活性无明显影响。Tet抑制炎症渗出的作用与其增加白细胞cAMP浓度的作用呈线性相关 ;其增加白细胞cAMP浓度的作用则与其抑制PDE活性呈线性相关 ;后者与其降低 [Ca2 + ] i 呈线性相关。在体外 ,Tet抑制细胞外Ca2 + 和A2 31 87引起的PDE活性升高 ,其抑制作用可因细胞外钙浓度增加而逆转。结论　增加炎症白细胞cAMP浓度可能是Tet重要的抗炎作用机制之一 ;Tet主要通过降低炎症白细胞 [Ca2 + ] i从而抑制PDE活性并最终减少cAMP降解 。AIM To study relationship between effect of tetrandrine(Tet) on pleurisy and cAMP of inflammatory neutrophiles. METHODS A model of pleurisy was established with an intrapleural injection of carrageenan (Car, 10 mg·kg -1 ) into rats. Tet was administrated by ip at 30 min befor injection of carrageenan. The exudate, neutrophils appeared in the pleural cavity of rats at 8 h were measured with routine method and the dilution tube technique respectively. cAMP concentration, adenyl cyclase(AC) activity, phosphodiesterase(PDE) activity of neutrophils and cytosolic free calcium concentration([Ca 2+ ] i) in neutrophils were determined with radioimmunoassay, indirect method, enzyme radiochemical assay and fluorescence colorimetric analysis respectively. The regulation of extracellular Ca 2+ on effect of Tet on PDE activity of neutrophils was also assessed in vitro . RESULTS Tet (10～80 mg·kg -1 ,ip) dose dependently decreased the exudate, neutrophil immigration, PDE activity and [Ca 2+ ] i in neutrophils, and increased cAMP concentration of neutrophils, but did not alter AC activity. A linear relationship was found between the reduction in the exudate and neutrophil immigration by Tet and the increment in cAMP concentration of neutrophils by Tet( r =0 990 or 0 992, P = 0 009 9 or 0 007 6 ). The increment in cAMP concentration was significantly associated with the inhibition of PDE activity of neutrophils by Tet( r =0 985, P = 0 014 9 ), which was related to the reduction in [Ca 2+ ] i in neutrophils by Tet( r =0 994, P = 0 005 7 ). Tet antagonized the increase in PDE activity of neutrophils induced by the combination of extracellular Ca 2+ and A 23187 in vitro. Furthermore, the antagonism of Tet was reversed by the increase in extracellular Ca 2+ concentration. CONCLUSION Tet increases cAMP concentration of neutrophils mainly due to inhibition of PDE activity resulted from the decrease in [Ca 2+ ] i in neutrophils. It may

关 键 词：粉防己碱 炎症 嗜中性白细胞 环腺苷-磷酸 腺苷酸环化酶 磷酸二酯酶 钙 

分 类 号：R-332[医药卫生] R284.1