摘要
目的通过研究双氢青蒿素(dihydroartemisinin,DHA)对狼疮模型MRL/lpr小鼠肾脏病变和肾皮质Fractalkine(FKN)、NF-κB表达的作用,并与泼尼松的作用进行比较,以探讨青蒿素治疗狼疮性肾炎的可能作用机制,试图明了双氢青蒿素对狼疮性肾炎FKN表达的调节作用。方法选取32只12周龄的雌性MRL/lpr小鼠,随机分为4组:DHA组,每天给予DHA灌胃;泼尼松组,每天给予泼尼松(prednisone,P)灌胃;DHA+泼尼松组,每天给予DHA和泼尼松灌胃;正常对照组,每天给予生理盐水灌胃;共8周。通过光镜观察肾组织病理改变,通过RT-PCR检测肾皮质FKN和NF-κB p65 mRNA的表达,免疫组织化学染色法检测肾皮质FKN及NF-κB p65蛋白的表达。结果 MRL/lpr小鼠肾皮质中检测到FKN、NF-κB p65 mRNA和蛋白的表达,DHA可减少MRL/lpr小鼠的蛋白尿、改善肾功能、减轻肾脏病变。DHA下调MRL/lpr小鼠肾皮质中FKN、NF-κB p65 mRNA和蛋白的表达。结论双氢青蒿素可通过调节FKN和NF-κB的表达实现其对狼疮性肾炎的治疗作用,与泼尼松联用效果更佳。
This study aimed to explore the possible mechanism of artemisinin involved in the treatment of lupus nephritis and clarify the regulatory role of dihydroartemisinin （DHA） on fractalkine （FKN） expression in lupus nephritis by studying the effect of dihydroartemisinin on the FKN and NF-κB expression in the renal cortex of lupusprone MRL/lpr mice. Thirty-two female MRL/lpr mice at 12 weeks of age were randomly divided into four groups, which received a daily intragastrie administration for 8 weeks of DHA （DHA-treated mice）, prednisone （prednisone- treated mice）, DHA and prednisone （DHA＋prednisone mice） and normal saline （control mice）, respectively. Then renal pathological changes were observed by optical microscopy; the expression of FKN and NF-κB p65 mRNA in renal cortex were detected by RT-PCR. Expression of FKN and NF-κB p65 protein in renal cortex were detected by immnnohistochemical staining. Data showed that the FKN, NF-κB p65 mRNA and protein were expressed in the renal cortex of MRL/lpr mice. And the reduced proteinuria, improved kidney function and ameliorated renal lesions were found in the DHA-treated mice. Furthermore, the expression of FKN, NF-κB p65 mRNA and protein in the renal cortex of MRL/lpr mice were down-regulated by DHA treatment. In conclusion, DHA can alleviate lupus nephritis by regulating the expression of FKN and NF-κB, especially in combination with prednisone.
出处
《免疫学杂志》
CAS
CSCD
北大核心
2014年第7期617-622,共6页
Immunological Journal
基金
国家自然科学基金项目(81160013/H0111)
广西卫生厅中医药科技课题(GZPT1249
GZZC1243)
