首页|六味二至四妙丸调控NF-κB信号通路介导治疗狼疮性肾炎作用机制的研究

六味二至四妙丸调控NF-κB信号通路介导治疗狼疮性肾炎作用机制的研究

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目的:探讨六味二至四妙丸(LWEZSMW)调控NF-κB信号通路改善狼疮性肾炎的效应机制。方法:50只MRL/lpr自发性狼疮小鼠随机分为5组:模型组、阳性药物组(泼尼松龙2 mg·kg-1)、六味二至四妙丸低剂量组(9。45 g·kg-1)、中剂量组(18。90g·kg-1)和高剂量组(37。80g·kg-1)。每组10只,连续给药干预35d后,考马斯亮蓝法检测各组小鼠蛋白尿水平。H&E染色检测小鼠肾脏病理损伤程度;免疫荧光检测各组小鼠肾脏免疫复合物沉积水平。流式细胞术检测各组小鼠脾脏和淋巴结CD11b+单核细胞比例。Western blot检测肾组织中p-IKB、p-NF-KB蛋白表达水平。结果:六味二至四妙丸药物干预后可显著减轻狼疮肾组织病理损伤,减少肾脏免疫复合物沉积,降低蛋白尿水平(P<0。05);与模型组比较,六味二至四妙丸高剂量组淋巴细胞中CD11b+炎症细胞比例显著降低(P<0。01),肾组织中p-IKB、p-NF-KB蛋白表达水平显著低于模型组(P<0。05)。结论:六味二至四妙丸对狼疮性肾炎具有明显保护效应,其机制可能与抑制NF-κB信号通路介导炎症反应有关,为六味二至四妙丸临床治疗系统性红斑狼疮(systemic lupus erythematosus,SLE)提供科学依据和生物学基础。
Study on the mechanism of action of Liuwei Erzhi Simiao Pill on Attenuates lupus nephritis by regulating NF-κB signaling pathway
OBJECTIVE To investigate the regulation of Liuwei Erzhi Simiao Pill(LWEZSMW)on NF-KB signaling path-way to improve lupus nephritis.METHODS Fifty MRL/lpr spontaneous lupus mice were randomly divided into 5 groups:model group,positive drug group(prednisolone 2 mg·kg-1)and LWEZSMW low dose group(9.45 g·kg-1),medium dose group(18.90 g·kg-1)and high dose group(37.80 g·kg-1)with 10 mice in each group.After 35 days of drug intervention,pro-teinuria was detected by Camas Brilliant Blue method,the degree of kidney pathological damage was detected by H&E staining,and the level of immune complex deposition was detected by immunofluorescence.Flow cytometry was used to detect the propor-tion of CD11b+ monocytes in the spleen and lymph nodes,The protein levels of p-IκB,NF-κB in the renal tissues were deter-mined by Western blot.RESULTS MRL/lpr mice treated with LWEZSMW showed significant reduction in renal damage.The proteinuria level,the deposition of immune complexes in the kidney and the proportion of lymphocytes and splenic lymphocytes CD11b+ inflammatory cells was significantly reduced in the high-dose group of LWEZSMW compared with the model group(P<0.05 or P<0.01);Meanwhile,the protein level of p-IκB、p-NF-κB were significantly reduced in the high-dose group(P<0.05).CONCLUSION LWEZSMW can significantly alleviates lupus nephritis,and its underlying mechanism may be related to inhibit-ing NF-KB signaling pathway-induced inflammatory response,providing a scientific basis and biological foundation for LWEZSMW clinical treatment of systemic lupus erythematosus(SLE).

Liuwei Erzhi Simiao Pillsystemic lupus erythematosuslupus nephritisNF-κB signaling pathway

李松梅、张玲忠、尹蔚萍、马殿飞、吴招、邹楠婷、李小丝、万春平、夏杰

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云南中医药大学第一临床医学院,云南昆明 650021

六味二至四妙丸 系统性红斑狼疮 狼疮性肾炎 NF-κB信号通路

云南省科技厅-云南中医药大学应用基础研究联合专项资金项目云南省科技厅-云南中医药大学应用基础研究联合专项资金项目云南省教育厅治疗痹症中医中药工程研究中心项目云南省科技人才和平台计划云南省第五批中医药师带徒项目

2019FF002-045202001AZ070001-059202101AZ070001-1162023GYB08202105AG070012云卫中医发展发[2020]2号

2024

中国医院药学杂志
中国药学会

中国医院药学杂志

CSTPCD北大核心
影响因子:1.198
ISSN:1001-5213
年,卷(期):2024.44(2)
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