硫酸羟氯喹治疗MRL/lpr狼疮鼠的疗效研究
The effect of hydroxychloroquine treatment on MRL/lpr lupus mice
目的 探讨硫酸羟氯喹(HCQ)对MRL/lpr狼疮鼠的疗效及作用机制.方法 MRL/lpr鼠随机分为HCQ治疗组、青蒿琥酯(ART)治疗组和对照组.18周龄时HCQ组给予HCQ 150 mg·kg-1·d-1,ART组给予ART 50 mg·kg-1·d-1治疗14周.考马斯亮蓝法检测尿蛋白定量(24 h),酶联免疫吸附法(ELISA)检测抗双链DNA(dsDNA)抗体水平,观察肾脏病理改变,流式细胞术检测脾脏和淋巴结中CD4+Foxp3+T细胞百分率.结果 ①尿蛋白定量(24 h)28周时HCQ组[(2.5±2.0)mg]和ART组[(2.4±2.0)mg]低于对照组[(4.8±3.2)mg](P<0.05),30周时HCQ组[(2.8±1.1)mgj和ART组[(2.4±1.9)mg]显著低于对照组[(6.4±1.9)mg](P<0.01).②32周龄时HCQ组体质量[(41.4±1.6)g]显著高于对照组[(37.1±1.0)g](P<0.01),血清肌酐[(7.8±4.0)μmol/L]低于对照组[(12.5±2.3)μmol/L](P<0.05),血清抗dsDNA抗体水平[(3047±1025)U/ml]显著低于对照组[(6093±2935)U/ml](P<0.05).③HCQ组和ART组肾脏病理损伤较对照组减轻.④HCQ组[(2.3±0.7)%]和ART组[(2.2±0.5)%]脾脏中CD4+ Foxp3+T细胞百分率均显著高于对照组[(1.5±0.5)%](P<0.05),HCQ组[(0.68±0.33)%]和ART组[(0.97±0.28)%]淋巴结中CD4+Foxp3+T细胞百分率均显著低于对照组[(2.15±0.72)%](P<0.01 o结论 HCQ治疗MRL/lpr狼疮有效,可以改善肾脏病理损伤,降低尿蛋白.HCQ和ART均能上调脾脏中的CD4+Foxp3+T细胞百分率.
更多Objective To investigate the therapeutic effects and mechanisms of hydroxychloroquine (HCQ) in the MRL/lpr mice. Methods MRL/lpr mice were divided into HCQ, the artesunate (ART) and proteinuria was detected with Coomassi Brilliant blue method. Enzyme linked immunosorbent assay (ELISA) was used to measure the anti-doubM-stranded DNA (ds-DNA) antibody. Renal tissue sections were dyed By PAS methods. The percentage of CD4+ Foxp3+ T cells in the spleen and lymph nodes were detected by flow 2.0) mg groups were decreased than in the control group (4.8±3.2) mg (P<0.05). And it was also lower in the HCQ (2.8±1.1) mg and ART (2.4±1.9) mg group than in the control group (6.4±1.9) mg (P<0.01) at 30 in the control group (37.1±1.0) g (P<0.01), while serum creatinine decreased significantly (7.8±4.0) μmol/L than in the control group (12.5±2.3) μmol/L (P<0.05), and the serum anti ds-DNA antibodies levels (3047±renal damage in the HCQ group and in the ART group was Both significantly improved than that in the entages of CD4+ Foxp3+ T cells in spleen when compared with the control group (1.5±0.5)% (P<0.05). The mice in the HCQ group (0.68±0.33)% and in the ART group (0.97±0.28)% had higher percentages of CD4+ Foxp3+ T cells in lymph nodes as compared with control group (2.15±0.72)%(P<0.01). Conclusion HCQ is effective in treating MRL/lpr lupus mice. It can improve the pathologic lesions of lupus nephritis, reduce proteinuria and antibody production. Both HCQ and ART can up-regulate the percentage of CD4+ Foxp3+ T cells in spleen of MRL/lpr mice.
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