积雪草酸通过调控Nrf2/NF-κB治疗MRL/lpr小鼠狼疮性肾炎的实验研究  

Experimental study of asiatic acid on lupus nephritis in MRL/lpr mice by regulating Nrf2/NF-κB

作　　者：胡义阳[1] 杨忠明 HU Yi-Yang;YANG Zhong-Ming(First Hospital of Quanzhou,Quanzhou 362000,China)

机构地区：[1]泉州市第一医院,泉州362000

出　　处：《中国免疫学杂志》2021年第13期1587-1590,1596,共5页Chinese Journal of Immunology

摘　　要：目的:探讨积雪草酸对MRL/lpr狼疮肾炎小鼠肾损伤的影响,并分析其与核因子E2相关因子2(Nrf2)/核因子κB(NF-κB)信号通路的相关性。方法:野生型小鼠为正常组,对MRL/lpr小鼠随机进行生理盐水[10 ml/(kg·d)]和积雪草酸[10 ml/(kg·d)]灌胃操作,分别作为对照组和实验组。连续22周,将小鼠处死后,收集肾脏组织进行HE染色、DHE染色、RT-PCR以及Western blot评价小鼠肾脏炎症反应和氧化应激水平。结果:积雪草酸可减缓MRL/lpr小鼠中的肾脏损伤,减少MRL/lpr小鼠中活性氧的产生。与正常组相比,MRL/lpr小鼠细胞核中的Nrf2蛋白水平显著低于正常对照组(P<0.05),积雪草酸处理的MRL/lpr小鼠Nrf2向细胞核的移位明显增加(P<0.05);与正常小鼠相比,MRL/lpr小鼠中的p47^(phox)水平显著增加(P<0.05),而给予积雪草酸治疗后的小鼠p47^(phox)水平明显降低。与正常组小鼠相比,MRL/lpr小鼠肾脏组织中NQO1和HO-1的mRNA水平显著降低(P<0.05)。免疫组化结果显示,与正常组相比,对照组CD3、F4/80和NF-κB表达水平显著增加(P<0.05),而积雪草酸处理的小鼠CD3、F4/80和NF-κB表达水平显著下降(P<0.05)。结论:积雪草酸可能通过Nrf2/NF-κB介导的抗氧化通路,抑制氧化应激,改善MRL/lpr小鼠肾损伤.Objective:To investigate the effect of Asiatic acid on kidney injury in mice with MRL/lpr lupus nephritis and analyze its correlation with nuclear factor E2-related factor 2(Nrf2)/nuclear factorκB(NF-κB)signal pathway.Methods:Wild-type mice were used as normal group,and MRL/lpr mice were randomly given normal saline[10 ml/(kg·d)]and Asiatic acid[10 ml/(kg·d)],which were used as control group and experimental group respectively.After 22 weeks,the mice were sacrificed,the kidney tissues were collected for HE staining,DHE staining,RT-PCR and Western blot to evaluate the level of inflammation and oxidative stress in the kidneys.Results:Asiatic acid reduced kidney injury and production of reactive oxygen species in MRL/lpr mice.Compared with normal group,the level of Nrf2 protein in nucleus of MRL/lpr mice was significantly lower than that of normal control group(P<0.05),and the shift of Nrf2 to nucleus of MRL/lpr mice treated with Asiatic acid was significantly increased(P<0.05).Compared with normal mice,the level of p47phoxin MRL/lpr mice increased significantly(P<0.05),the p47phox level of mice treated with asiatic acid was significantly reduced(P<0.05).Compared with normal mice,the mRNA levels of NQO1 and HO-1 in the kidney tissue of MRL/lpr mice were significantly reduced(P<0.05).Immunohistochemical results showed that the expressions of CD3,F4/80 and NF-κB in control group were significantly increased(P<0.05),while those in mice treated with asiatic acid were significantly decreased(P<0.05).Conclusion:Asiatic acid can prevent lupus nephritis in MRL/lpr mice through Nrf2/NF-κB signaling pathway.

关 键 词：狼疮性肾炎 NRF2 氧化应激 积雪草酸 

分 类 号：R593.24[医药卫生—内科学]