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 artesuna...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.展开更多
目的探讨解毒祛瘀滋肾方中3味解毒中药单用或不同组合对MRL/lpr小鼠血清及肾组织调节正常T细胞表达和分泌活性因子(regulated on activation normal T cell expressed and secreated,RANTES)表达的影响。方法 54只MRL/lpr小鼠随机分成9...目的探讨解毒祛瘀滋肾方中3味解毒中药单用或不同组合对MRL/lpr小鼠血清及肾组织调节正常T细胞表达和分泌活性因子(regulated on activation normal T cell expressed and secreated,RANTES)表达的影响。方法 54只MRL/lpr小鼠随机分成9组,每组6只,分别以青蒿、蛇舌草、升麻、青蒿蛇舌草、青蒿升麻、蛇舌草升麻、青蒿蛇舌草升麻煎剂、泼尼松混悬液、生理盐水灌胃,12周后取血及肾脏,以ELISA法及RT-PCR法分别检测血清和肾组织中RANTES的表达。结果治疗12周末,泼尼松组的RANTES表达水平均显著下降;青蒿、升麻对RANTES表达水平的抑制作用不明显,蛇舌草、青蒿联合蛇舌草、青蒿联合升麻、蛇舌草联合升麻虽均有一定的抑制作用,但均不如青蒿联合蛇舌草及升麻的抑制作用明显。结论青蒿、蛇舌草、升麻三药联用能抑制RANTES的表达。展开更多
[目的]观察解毒祛瘀滋阴方对MRL/lpr狼疮鼠巨噬细胞TLR4信号通路的影响。[方法]MRL/lpr狼疮鼠分为模型组、强的松组、解毒祛瘀滋阴方组(以下简称:中药组)以及强的松加中药组(以下简称:中西药结合组),分别以生理盐水、强的松、解毒祛瘀...[目的]观察解毒祛瘀滋阴方对MRL/lpr狼疮鼠巨噬细胞TLR4信号通路的影响。[方法]MRL/lpr狼疮鼠分为模型组、强的松组、解毒祛瘀滋阴方组(以下简称:中药组)以及强的松加中药组(以下简称:中西药结合组),分别以生理盐水、强的松、解毒祛瘀滋阴方中药和强的松加解毒祛瘀滋阴方中药灌胃4周,收集肺、腹腔、脾脏巨噬细胞,RT-PCR检测相关基因的表达。[结果]经强的松治疗后狼疮鼠肺巨噬细胞TLR4 mRNA和脾巨噬细胞TLR4蛋白都显著升高(P<0.05),而中西药结合组则可以显著降低升高的脾巨噬细胞TLR4蛋白水平(P<0.05)。强的松还可以显著降低肺、腹腔巨噬细胞MyD88、IFN-α、iNOS mRNA等TLR4下游分子的表达(P<0.05),而中西药结合组可以显著升高已经降低的肺巨噬细胞MyD88 m RNA的表达(P<0.05)。[结论]MRL/lpr狼疮鼠应用糖皮质激素后,巨噬细胞TLR4信号通路发生改变,解毒祛瘀滋阴方中药可以降低糖皮质激素造成的TLR4蛋白的异常表达。展开更多
基金The study was supported by grants from Chinese National Natural Science Foundation(No.30972736)Chinese National 115 Supporting Program(2008BAI59B02)+2 种基金Jiangsu Province 135 Talent Foundation(RC2007002)Jiangsu Province Natural Science Foundation(No.09KJB320010)The Six Projects Sponsoring Talent Summits of Jiangsu Province.
文摘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.
文摘目的探讨解毒祛瘀滋肾方中3味解毒中药单用或不同组合对MRL/lpr小鼠血清及肾组织调节正常T细胞表达和分泌活性因子(regulated on activation normal T cell expressed and secreated,RANTES)表达的影响。方法 54只MRL/lpr小鼠随机分成9组,每组6只,分别以青蒿、蛇舌草、升麻、青蒿蛇舌草、青蒿升麻、蛇舌草升麻、青蒿蛇舌草升麻煎剂、泼尼松混悬液、生理盐水灌胃,12周后取血及肾脏,以ELISA法及RT-PCR法分别检测血清和肾组织中RANTES的表达。结果治疗12周末,泼尼松组的RANTES表达水平均显著下降;青蒿、升麻对RANTES表达水平的抑制作用不明显,蛇舌草、青蒿联合蛇舌草、青蒿联合升麻、蛇舌草联合升麻虽均有一定的抑制作用,但均不如青蒿联合蛇舌草及升麻的抑制作用明显。结论青蒿、蛇舌草、升麻三药联用能抑制RANTES的表达。
文摘[目的]观察解毒祛瘀滋阴方对MRL/lpr狼疮鼠巨噬细胞TLR4信号通路的影响。[方法]MRL/lpr狼疮鼠分为模型组、强的松组、解毒祛瘀滋阴方组(以下简称:中药组)以及强的松加中药组(以下简称:中西药结合组),分别以生理盐水、强的松、解毒祛瘀滋阴方中药和强的松加解毒祛瘀滋阴方中药灌胃4周,收集肺、腹腔、脾脏巨噬细胞,RT-PCR检测相关基因的表达。[结果]经强的松治疗后狼疮鼠肺巨噬细胞TLR4 mRNA和脾巨噬细胞TLR4蛋白都显著升高(P<0.05),而中西药结合组则可以显著降低升高的脾巨噬细胞TLR4蛋白水平(P<0.05)。强的松还可以显著降低肺、腹腔巨噬细胞MyD88、IFN-α、iNOS mRNA等TLR4下游分子的表达(P<0.05),而中西药结合组可以显著升高已经降低的肺巨噬细胞MyD88 m RNA的表达(P<0.05)。[结论]MRL/lpr狼疮鼠应用糖皮质激素后,巨噬细胞TLR4信号通路发生改变,解毒祛瘀滋阴方中药可以降低糖皮质激素造成的TLR4蛋白的异常表达。
基金The project supported by National Natural Science Foundation of China(31100576)Key Scientific and Technological Project of Wenzhou City(Y20090240)Scientific and Technological Project of Wenzhou City(Y20100287)~~
