青蒿琥酯治疗MRL/lpr狼疮鼠肾炎的病理变化及机制

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

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。

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 G3 in kidney in artesunate group and in CTX group decreased significantly in comparison with the control group. （3） The expressions of VEG-F 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.