重组人白细胞介素-1受体拮抗药对豚鼠离体呼吸道平滑肌的影响

Effects of recombinant human interleukin-1 receptor antagonist on guinea-pig isolated airway smooth muscle

目的 观察人重组白细胞介素 1受体拮抗剂 (IL 1ra)对正常和卵白蛋白致敏豚鼠离体肺条、气管平滑肌的影响。方法 应用离体器官装置、张力换能器、MedLab记录系统测定肺条和气管平滑肌的张力。结果 ①IL 1ra对正常豚鼠离体肺条和气管平滑肌有直接松弛作用 ,EC50 分别为1 2 9ⅹ 10 -7mol·L-1和 8 0 6× 10 -8mol·L-1;并对卵白蛋白致敏的豚鼠肺条和气管平滑肌也有直接的松弛作用 ,EC50 分别为 2 6 1× 10 -7mol·L-1和 5 88× 10 -7mol·L-1,但致敏豚鼠呼吸道平滑肌对IL 1ra的敏感性要比正常豚鼠低。②IL 1ra(10 -9～ 10 -5mol·L-1)可剂量依赖性地抑制致痉剂组胺对正常豚鼠肺条和气管平滑肌的收缩作用 (P <0 0 1)。③IL 1ra能抑制卵白蛋白攻击引起的肺条和气管平滑肌的收缩 ,IC50 分别为 7 83ⅹ 10 -7mol·L-1和 4 4 8ⅹ 10 -7mol·L-1。结论 IL 1ra对正常。

AIM To study the effects of recombinant human IL 1 receptor antagonist (IL 1ra) on isolated airway smooth muscle tissue. METHODS Changes of isolated organ's tension were monitored with force displacement transducer and MedLab recording system. RESULTS ①IL 1ra haddirect relaxant effect in normal and ovalbumin sensitized pulmonary as well as tracheal smooth muscle. The mean EC 50 values were 1 29×10 -8 mol·L -1 and 8 06×10 -8 mol·L -1 in normal pulmonary and tracheal smooth muscle, but the mean EC 50 values were 2 61×10 -7 mol·L -1 and 5 88×10 -7 mol·L -1 in ovalbumin sensitized pulmonary and tracheal smooth muscle. Therefore the relaxation responses of sensitized airway smooth muscle to IL 1ra were lower than those of normal pulmonary and tracheal smooth muscle.②IL 1ra(10 -9 ～10 -5 mol·L -1 ) concentration dependently inhibit contraction responses to histamine(10 -3 mol·L -1 ) in normal pulmonary and tracheal smooth muscle, compared with administrating solvent PBS group ( P <0 01). ③IL 1ra significantly inhibit the contraction of sensitized pulmonary and tracheal smooth muscle induced by antigen ovalbumin. The mean IC 50 values were 7 83×10 -7 mol·L -1 and 4 48×10 -7 mol·L -1 respectively. CONCLUSION IL 1ra had relaxant effect in normal, contracted and sensitized airway smooth muscle.