Department of Rheumatology and Immunology, the Affiliated Drum Tower Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing, Jiangsu 210008, China.
Cell Mol Immunol. 2009 Dec;6(6):461-7. doi: 10.1038/cmi.2009.58.
Recent evidence indicates that artesunate has immunomodulatory properties that might be useful for treating autoimmune disease. In this study, we conducted a pilot study and explored the effect and mechanism of artesunate on the treatment of systemic lupus erythematosus using an MRL/lpr murine model. MRL/lpr mice were divided into control, cyclophosphamide (CTX) and artesunate treatment groups. Blood was collected to measure serum levels of creatinine, antinuclear antibody (ANA) and anti-double-stranded DNA (anti-dsDNA) antibody. Twenty-four-hour urine was collected to measure levels of proteinuria. The concentration of monocyte chemotactic protein-1 (MCP-1) in serum and urine was measured. The expression of MCP-1 in kidney was detected by Western blot and immunohistochemistry assay, respectively. The expression of B cell activating factor (BAFF) in spleen was determined by real time-PCR and immunoblotting. We found that artesunate significantly increased the survival rate, body weight and blood leukocyte counts, and reduced the serum levels of ANA and anti-dsDNA antibody titer, 24 h urinary protein, and serum creatinine. Our results indicated that artesunate could decrease MCP-1, major pro-inflammation cytokine, in serum, urine and kidney. We also found that the level of BAFF, the major B cell activation factor, was decreased in artesunate treated MRL/lpr mice. Its efficacy was comparable with that of CTX in this study. Taken together, we have demonstrated that artesunate can inhibit the progression of disease and reverse the pathologic lesion of lupus nephritis.
最近的证据表明，青蒿琥酯具有免疫调节特性，可能对治疗自身免疫性疾病有用。在这项研究中，我们使用 MRL/lpr 小鼠模型进行了一项初步研究，探讨了青蒿琥酯治疗系统性红斑狼疮的效果和机制。MRL/lpr 小鼠分为对照组、环磷酰胺（CTX）组和青蒿琥酯治疗组。采集血液以测量血清肌酐、抗核抗体（ANA）和抗双链 DNA（抗 dsDNA）抗体水平。收集 24 小时尿液以测量蛋白尿水平。测量血清和尿液中单核细胞趋化蛋白-1（MCP-1）的浓度。通过 Western blot 和免疫组化分别检测肾脏中 MCP-1 的表达。通过实时 PCR 和免疫印迹测定脾脏中 B 细胞激活因子（BAFF）的表达。我们发现青蒿琥酯显著提高了存活率、体重和白细胞计数，并降低了血清 ANA 和抗 dsDNA 抗体滴度、24 小时尿蛋白和血清肌酐水平。我们的结果表明，青蒿琥酯可以降低 MCP-1，一种主要的促炎细胞因子，在血清、尿液和肾脏中的水平。我们还发现，青蒿琥酯治疗的 MRL/lpr 小鼠中 BAFF 的水平，一种主要的 B 细胞激活因子，降低了。其疗效在本研究中与 CTX 相当。总之，我们已经证明青蒿琥酯可以抑制疾病的进展并逆转狼疮性肾炎的病理损伤。
