重组人白细胞介素-1受体拮抗剂治疗骨关节炎的药效学分析
Pharmacodynamics of recombinant human interleukin-1 receptor antagonist in treatment of osteoarthritis
刘畅 1刘玉林 2刘涵 2顾笑宇 2俞露 2郁仁龙 3何秀霞4
作者信息
- 1. 长春理工大学,吉林长春 130022;长春生物制品研究所有限责任公司,吉林长春 130012
- 2. 长春生物制品研究所有限责任公司,吉林长春 130012
- 3. 苏州西山中科药物研究开发有限公司,江苏苏州 215104
- 4. 长春理工大学,吉林长春 130022
- 折叠
摘要
目的 观察重组人白细胞介素-1受体拮抗剂(recombinant human interleukin-1 receptor antagonist,rhIL-1 Ra)对碘乙酸钠(sodium iodoacetate,MIA)诱导的骨关节炎(osteoarthritis,OA)大鼠的治疗作用.方法 将雌性Wistar大鼠根据热痛阈值均衡分为正常对照组(11只)和造模组(55只),造模3d后,依据左后肢膝关节肿胀率将造模组随机分为溶剂对照模型组(安慰剂)及原料药低(9 mg/kg rhIL-1Ra)、高(18 mg/kg rhIL-1Ra)剂量组,每组12只,均经颈部皮下注射给药,1mL/kg,1次/d,连续14d.分别于造模前后3 d及首次给药后2、4、7、14d,测量左后肢膝关节同一处的直径,计算肿胀度、肿胀率及肿胀抑制率;取左后肢膝关节标本固定,经石蜡包埋、切片后,番红O染色,显微镜下进行病理损伤评分.结果 造模3d后,除正常对照组外,其他各组大鼠膝关节肿胀率均约达30％;与溶剂对照模型组比较,原料药低剂量组肿胀度和肿胀率在给药后2、4 d(1.52±0.38、1.26±0.43)时均降低(t分别为1.924、1.945,P均＜0.05),而原料药高剂量组在给药后2、4、7 d(1.51±0.37、1.15±0.24、1.14±0.39)时均显著降低(t分别为2.976、2.874、2.902,P均＜0.01).与溶剂对照模型组比较,原料药低、高剂量组(8.33±1.86、8.17±2.79)大鼠关节软骨病变程度相似,病理评分统计结果显示有轻微降低(t=1.814,P均＞0.05),造模成功.结论 给药14 d,高剂量rhIL-1Ra能显著减轻MIA诱导的大鼠骨关节炎急性期关节肿胀,但对MIA诱导的慢性骨关节炎的痛觉感受无明显影响,且未见其显著逆转MIA诱导的膝关节软骨损伤.
Abstract
Objective To observe the therapeutic effect of recombinant human interleukin-1 receptor antagonist(rhIL-1Ra)on osteoarthritis(OA)induced by sodium iodoacetate(MIA)in rats.Methods Female Wistar rats were divided into normal control group(11 rats)and model group(55 rats)according to the threshold of heat pain.After 3 d of modeling,the model group was randomly divided into solvent control model group(placebo),low-dose group(9 mg/kg rhIL-1Ra)and high-dose group(18 mg/kg rhIL-1Ra),with 12 rats in each group,according to the swelling rate of the left hindlimb knee joint,which were subcutaneously injected through neck,1 mL/kg once a day for 14 consecutive days.The diameter of the left hindlimb knee joint was measured 3 d before and after modeling and 2,4,7 and 14 d after the initial administration,and the swelling degree,swelling rate and swelling inhibition rate were calculated.The knee joint specimens of the left hindlimb were fixed,embedded in paraffin,sectioned,then stained with safranin O,and scored the pathological lesion under microscope.Results After 3 d of modeling,the swelling rates of knee joint of rats in all groups except normal control group reached about 30％.Compared with the solvent control model group,the swelling degree and swelling rate in the low-dose group decreased at both 2 and 4 d(1.52±0.38 and 1.26±0.43)(t=1.924,1.945,each P＜0.05)after adminis-tration,while those in the high-dose group all decreased significantly at 2,4 and 7 d(1.51±0.37,1.15±0.24,and 1.14±0.39)(t=2.976,2.874,2.902,each P＜0.01).Compared with the solvent control model group,the degrees of articular cartilage lesions in the low and high dosage groups(8.33±1.86,8.17±2.79)were similar,and the statistical results of pathological scores showed a slight decrease(t=1.814,each P＞0.05),indicating that the model was estab-lished successfully.Conclusion After 14 d of administration,high dose of rhIL-1Ra significantly reduced the knee joint swelling in acute stage of MIA-induced osteoarthritis in rats,but had no significant effect on the pain perception in MIA-induced chronic knee arthritis,and did not significantly reverse the knee cartilage injury induced by MIA.
关键词
重组人白细胞介素-1受体拮抗剂/骨关节炎/热痛阈值/碘乙酸钠Key words
Recombinant human interleukin-1 receptor antagonist(rhIL-1Ra)/Osteoarthritis(OA)/Heat pain threshold/Sodium iodoacetate(MIA)引用本文复制引用
出版年
2024
NETL
NSTL
万方数据