滨蒿内酯抑制组胺诱导的哮喘豚鼠气道平滑肌细胞内钙释放  

Scoparone Suppressed Histamine-induced Intracellular Ca^(2+) Release in Airway Smooth Muscle Cells from Asthmatic Guinea-pig

作　　者：滕赞[1] 王嫘[2] 李智[3] 

机构地区：[1]中国医科大学附属第一医院肿瘤内科,辽宁沈阳110001 [2]中国医科大学附属第一医院老年病科 [3]中国医科大学药学院药物毒理学教研室

出　　处：《实用预防医学》2011年第12期2245-2248,共4页Practical Preventive Medicine

基　　金：国家自然科学基金资助项目(30470765)

摘　　要：目的研究滨蒿内酯(scoparone,Sco)剂量依赖性舒张气管平滑肌及降低气道高反应性的可能作用靶点及途径,为进一步将其开发成为平喘的中药新药提供药理学理论依据。方法建立卵蛋白诱导的哮喘豚鼠模型,通过离体豚鼠气管环的舒缩实验及应用倒置荧光显微成像系统测定培养的ASMCs[Ca2+]i浓度的方法,分析Sco预先给药及直接作用对ASMCs[Ca2+]i的影响。结果显示无论细胞外含钙或无钙,组胺具有收缩ASM环及升高培养的ASMC[Ca2+]i作用,哮喘组明显高于对照组(P<0.05),预先给予Sco组与对照组比较差异无统计学意义(P>0.05);在细胞外无钙时10-4M Sco直接作用培养的ASMCs,可明显抑制各浓度组胺诱导的ASMCs[Ca2+]i的上升(P<0.05)。结论预先给予Sco及直接作用都可不同程度改善哮喘豚鼠ASMCs对不同浓度组胺的高反应性,这可能与Sco抑制哮喘豚鼠ASMCs IP3介导的内钙释放途径有关。Objective Scoparone（Sco） possesses anti-inflammatory and calcium antagonistic effects and it could significantly relax airway smooth muscle（ASM） and decrease cytoplasmic Ca2＋ concentration（i） of ASM cells（ASMCs）.In this study,the possible pathway of the calcium antagonistic effects of Sco was investigated. Methods ASM strips and cells were derived from normal or ovalbumin-induced asthmatic or Sco pretreated asthmatic guinea-pigs and ASMCs were cultured for 5 to 7 days.Using Fluo-3/AM staining and a fluorescence spectrophotometer system,the changes of intracellular calcium of cultured ASMCs from each group were measured with or without Sco and histamine. Results The results showed that ASM strips and primary cultured ASMCs from asthmatic guinea-pig maintained the hyper-responsiveness to histamine with different concentrations（P0.05）,and the group of asthmatic guinea-pig pretreated with Sco had the similar responsiveness to histamine as compared with control group（P0.05）.10-4M Sco also significantly inhibited histamine induced Ca2＋ release in cultured ASMCs（P 0.01）. Conclusions Sco shows excellent protection in guinea-pig against histamine-induced ASM contraction by down-regulating hyperactivity of IP3-induced Ca2＋ release in ASMCs from asthmatic guinea pigs.

关 键 词：滨蒿内酯 哮喘 细胞内钙释放 组胺 IP3 

分 类 号：R562.25[医药卫生—呼吸系统]