摘要
目的探讨青蒿琥酯对MRL／lpr狼疮鼠的疗效及作用机制。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125mg·kg^-1·d^-1治疗16周，CTX组给予CTX100ms／kg×2d腹腔注射。考马斯亮蓝法检测尿蛋白定量（24h），间接免疫荧光法检测血清抗核抗体（ANA）、抗双链DNA（dsDNA）抗体滴度，过碘酸雪夫（PAs）染色观察病理改变，免疫荧光检测补体C3沉积，反转录-聚合酶链反应（EmPCR）检测小鼠脾脏B细胞刺激因子（BAFF）mRNA的表达水平。结果①24、28、32周尿蛋白定量（24h）青蒿琥酯组[（4．9±1．2），（5．2±1．0），（6．4±1．2）mg]显著低于对照组[（9．0±1．3），（9．3±0．6），（10．0±1．6）mg]（均P〈0．01），28、32周尿蛋白定量（24h）青蒿琥酯组显著低于CTX组[（5．2±1．0）vs（7．7±1．0），（6．4±1．2）vs（9．6±1．9）mg]（P均〈0．05）。②32周龄时青蒿琥酯组体质量[（36．3±5．5）g]高于对照组[（32．8±3．0）g]（P〈0．05），血清肌酐青蒿琥酯组[（15．9±2．4）μmol/L]显著低于对照组[（20．8±5．1）μmol／L]（P〈0．05）。③青蒿琥酯组和CTX组肾脏病理损伤较对照组减轻，肾脏内补体C3沉积较对照组减少。④青蒿琥酯组脾脏BAFF mRNA表达（0．81±0．05）和CTX组脾脏BAFF mRNA表达（0．74±0．13）均低于对照组（0．98±0．07）（P〈0．05）。结论青蒿琥酯治疗MRI／Ipr狼疮鼠有效，可以改善肾脏病理损伤，降低尿蛋白，延长狼疮鼠生存期。抑制BAFF的产生可能是青蒿琥酯治疗MRL/lpr有效的机制之一。
Objective To investigate the therapeutic effect and mechanism of artesunate in the MRL/ lpr mice. Methods MRL/ lpr mice were divided into cyclophosphamide （CTX）, artesunate and control groups. At the age of 16 weeks, the mice in the artesunate group were given artesunate （125 mg·kg^-1·d^-1） for 16 weeks, the mice in CTX group were intraperitoneally injected CTX 100 mg·kg×2 d. The 24-hour proteinuria was detected with Coomassi blue method. Indirect immunofluorescence was used to measure the antinuclear antibody （ANA） and anti-double-stranded DNA （ds-DNA） antibody.Renal tissue section was dyed by PAS methods. Indirect immunofluorescence was used to detect complement C3. B cell activating factor （BAFF） gene expression in spleen was examined by RT-PCR. Results ① At 24, 28, 32 weeks, the 24 hours proteinuria in the artesunate group [（4.9±1.2）, （5.2±1.0）, （6.4±1.2） mg, respectively] was significantly decreased than that in the control group [ （9.0±1.3）, （9.3±0.6）, （10.0±1.6） mg, respectively ] （P〈0.01）, and at 28, 32 weeks, it was also significantly decreased in artesunate group than in CTX group [（5.2±1.0） vs （7.7±1.0）, （6.4±1.2） vs （9.6±1.9） mg] （P〈0.05）. ② At 32 weeks, the bodyweight of the artesunate group （36.3±5.5） g, was increased significantly than the control group [（32.8±3.0） g,P〈0.05]. Serum creatinine decreased significantly in the artesunate group （15.9±2.4）μmol/L than in the control group [（20.8±5.1） μmol/L, P〈0.05 ]. ③The degree of renal damage in the artesunate group and in the CTX group was both significantly decreased than control group. The deposition of complement C3 in kidney in artesunate group and in CTX group were both significantly decreased than control group. ④ The expressions of BAFF mRNA of spleen in artesunate group（0.81±0.05 ） and in CTX group （0.74±0.13） were both significantly decreased than control group （0.98±0.07） （P〈0.05）. Conclusion Artesunate is effective in treating MRL/lpr mice. It can improve the pathologic lesion of lupus nephritis, reduce proteinuria and prolong life span. Inhibition the production of BAFF may be one of the mechanisms of artesunate in the treatment of MRL/lpr mice.
出处
《中华风湿病学杂志》
CAS
CSCD
2008年第3期177-181,217,共6页
Chinese Journal of Rheumatology
基金
基金项目：江苏省135重点人才培养基金资助项目（RC2002003）
