早期使用羟氯喹对系统性红斑狼疮模型鼠内皮功能障碍的影响

Effect of early use of hydroxychloroquine on endothelial dysfunction in model rats with systemic lupus erythematosus

目的观察早期使用羟氯喹(HCQ)对系统性红斑狼疮(SLE)模型鼠内皮功能障碍(ED)的影响,探讨其作用靶点。方法将120只健康雌性大鼠随机分为对照组、模型组、羟氯喹组。除对照组外,其余各组使用降植烷诱导雌性鼠造成SLE模型。羟氯喹组造模成功后开始给药,共计30周。分别在12、18、24、30周后测定各组大鼠24 h尿蛋白含量和抗双链DNA自身抗体浓度,评估血管内皮依赖性舒张因子(NO)的可用性。结果从18周龄开始,羟氯喹组24 h尿蛋白含量较模型组明显减少,dsDNA自身抗体的血清滴度下降。模型组SLE雌性鼠NO的可用性逐渐降低,HCQ给药使24周龄组NO的可用性正常化,并且在30周龄组中部分改善。结论早期HCQ治疗能够通过减少NO的可用性受损发挥血管保护作用。

Objective To observe the effect of early use of hydroxychloroquine(HCQ)on endothelial dysfunction(ED)in model rats with systemic lupus erythematosus(SLE)and to explore its target.Methods Totally 120 healthy female rats were randomly divided into control group,model group and HCQ group.Except control group,the other two groups used pristane to induce SLE model in female rats.HCQ group was administered for 30 weeks after the model was successfully established.The 24-hour proteinuria content and anti-double-stranded DNA autoantibody concentration of rats in each group were measured after 12,18,24 and 30 weeks,and the availability of endothelium-dependent relaxation factor(NO)was evaluated.Results From the age of 18 weeks,the 24 hour-urine protein content of HCQ group was significantly reduced compared with model group,and the serum titer of dsDNA autoantibody was decreased.The NO availability of female SLE rats in model group decreased gradually,and HCQ administration normalized NO availability in 24-week-old group and partially improved it in 30-week-old group.Conclusion Early HCQ treatment can exert vascular protection by reducing the impaired availability of nitric oxide(NO).