白芍总苷对雷公藤多苷治疗狼疮性肾炎减毒增效作用的实验研究

Toxicity-reducing and Action-enhancing Effects of Total Glucosides of Paeony on Tripterygium Glycosides in Treating Lupus Nephritis

目的探讨白芍总苷(TGP)对雷公藤多苷(TG)治疗狼疮性肾炎(lupus nephritis,LN)小鼠的减毒增效作用。方法取B6D2F1代杂交小鼠建立慢性移植物抗宿主病(cGVHD)LN小鼠模型,将成模小鼠随机分为3组,模型(LN)组、TG组、TG+TGP组,每组6只,另设正常对照组6只。TG组给予雷公藤多苷灌胃,剂量为30mg·kg-1·d-1;TG+TGP组给予雷公藤多苷及白芍总苷灌胃,剂量分别为30mg·kg-1·d-1和200mg·kg-1·d-1,正常对照组和LN组分别给予等容量生理盐水灌胃,每日给药1次,各组给药方法及时间均相同,共计4周。实验结束时,观察并比较各组小鼠的24h尿蛋白排泄率(UPE)、肝肾功能及肾脏病理改变。结果与LN组相比,TG组、TG+TGP组小鼠的24hUPE、尿素(BUN)、肌酐(SCr)显著降低(P<0.05或P<0.01),TG+TGP组显著低于TG组(P<0.05或P<0.01)。与LN组相比,TG组小鼠的ALT、AST和MDA均显著增高(P<0.01),SOD、GSH均显著降低(P<0.05或P<0.01)。与TG组相比,TG+TGP组的ALT、AST、MDA均显著降低(P<0.01),SOD、GSH均显著增高(P<0.01)。TG+TGP组对LN肾脏病理改变的改善作用显著优于TG组(P<0.05或P<0.01)。结论TGP对TG治疗LN具有减毒增效的作用。

Objective To investigate the toxicity - reducing and action - enhancing effects of total glucosides of paeony （TGP） on tripterygium glycosides （TG） in treating murine lupus nephritis （LN）. Methods Chronic graft -versus -host disease （cGVHD） routine LN model was established. Modeling mice were randomly divided into three groups： LN group, TGgroup （in the dose of 30 mg ·kg^-1·d^-1）, and TG＋TGPgroup （TG in the dose of 30 mg·kg^-1·d^-1 and TGP in the dose of 200 mg·kg^-1·d^-1）, 6 mice in each group. Another six normal mice served as control. Medication groups received corresponding medicine according to the experimental design, and mice in the normal control group and LN group received the same volume of saline, qd, for 4 weeks. After the treatment, the levels of 24 - hour urinary protein excretion （UPE）, blood urea nitrogen （BUN）, serum creatinine （SCr）, serum alanine transferase （ALT） and aspartate transferase fAST）, and contents of superoxide dismustase （SOD）, malondialdehyde （MDA）, and glutathione peroxidase （GSH - Px） in liver tissue homogenate were measured. Meanwhile, the pathologic changes of kidneys in each group were detected. Results Compared with LN group, levels of UPE, BUN and SCr in TG group and TG ＋ TGP group were decreased notablely （ P 〈 0.05 or P 〈 0.01 ）, and levels of above indexes in TG ＋ TGP group was lower than those in TG group （ P 〈 0.05 or P 〈 0. 01 ）. The levels of ALT, AST and MDA in TG group were increased significantly, and the levels of SOD and GSH were decreased markedly compared to LN group （ P 〈 0.05 or P 〈 0.01）. Compared with TG group, the levels of ALT, AST and MDA in TG ＋ TGP group were decreased significantly and the levels of SOD and GSH were increased remarkably （ P 〈 0.01 ）. The effect on improving the pathologic changes of kidneys in TG ＋ TGP group was better than that in TG group （ P 〈 0.05 or P 〈 0.01）. Conclusion TGP has toxicity - reducing and action - enhancing effects on TG in treating LN.