青蒿琥酯治疗MRL/lpr狼疮鼠肾炎的病理变化及机制

目的研究青蒿琥酯对MRL/lpr狼疮鼠肾炎的疗效,探讨青蒿琥酯治疗狼疮鼠肾炎的病理变化及机制,为临床用于治疗狼疮患者提供依据。方法MRL/lpr鼠随机分为青蒿琥酯治疗组、环磷酰胺(CTX)治疗组和对照组。16周龄时青蒿琥酯组给予青蒿琥酯125 mg/(kg.d)治疗16周,CTX组给予CTX 100 mg/kg×2 d腹腔注射。PAS染色观察病理改变,免疫荧光检测补体C3沉积,运用反转录-聚合酶链反应(RT-PCR)检测小鼠肾脏血管内皮生长因子(VEGF)的mRNA表达水平,用免疫组化法检测肾脏中VEGF的蛋白表达。结果①青蒿琥酯组和CTX组肾脏病理损伤较对照组明显减轻;②青蒿琥酯组和CTX组肾脏内补体C3沉积较对照组明显减少;③青蒿琥酯组肾脏VEGF mRNA表达(0.72±0.11)和CTX组肾脏VEGFmRNA表达(0.66±0.19)均低于对照组(0.92±0.06)(P<0.05);④青蒿琥酯组和CTX组肾脏VEGF表达比对照组明显减少。结论青蒿琥酯治疗MRL/lpr狼疮鼠可以改善肾脏病理损伤。抑制C3的沉积及VEGF的产生是青蒿琥酯治疗MRL/lpr狼疮鼠肾炎的有效的可能机制。

Pathological Change and Mechanism of Artesunate Treatment for Lupus Nephritis in MRL/lpr Mice

Objective To investigate the effects of artesnunate treatment for lupus nephritis of MRL/lpr mice,and explore the renal pathological changeand mechanism of artesunate therapy.Methods MRL/lpr mice were divided into cyclophosphamide(CTX),artesunate and control groups.When 16 weeks old,the mice in artesunate group were given artesunate [125 mg/(kg·d)]for 16 weeks,the mice in CTX group were intraperitoneally injected CTX 100 mg/kg×2 d.PAS dyed for pathological section,VEGF gene expression in kidney was examined by RT-PCR.The expression of VEGF protein in kidney was detected by immunohistochemistry.Results ① The degree of renal damage in artesunate group and in CTX group decreased more significantly than the control group.② The deposition of complement C3 in kidney in artesunate group and in CTX group decreased significantly in comparison with the control group.③ The expressions of VEGF mRNA of kidney in artesunate group(0.72±0.11) and in CTX group(0.66±0.19) decreased significantly in comparison with the control group(0.92±0.06)(P<0.05).④ The expressions of renal VEGF protein in artesunate group and in CTX group also decreased.Conclusion Artesunate has therapentic effects for lupus nephritis of MRL/lpr.The effect of artesunate on lupus neprtitis in MRL/lpr mice may be partly due to its inhibitory roles on the renal complement C3 deposition and VEGF production.