Lentivirus-mediated overexpressed NR4A1 monocytes in the treatment of lupus nephritis in lupus mice

Lin Jiayi

doi:10.13406/j.cnki.cyxb.002761

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Lentivirus-mediated overexpressed NR4A1 monocytes in the treatment of lupus nephritis in lupus mice

更新时间：2024-01-09

- Lentivirus-mediated overexpressed NR4A1 monocytes in the treatment of lupus nephritis in lupus mice
- Journal of Chongqing Medical University Vol. 46, Issue 12, Pages: 1448-1453(2021)
- 作者机构：
  
  福建医科大学附属协和医院检验科,福州,350001
- 作者简介：
- 基金信息：
- DOI：10.13406/j.cnki.cyxb.002761
  CLC： R593.24
- Published：2021，
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Lin Jiayi. Lentivirus-mediated overexpressed NR4A1 monocytes in the treatment of lupus nephritis in lupus mice. [J]. Journal of Chongqing Medical University 46(12):1448-1453(2021)
DOI：

Lin Jiayi. Lentivirus-mediated overexpressed NR4A1 monocytes in the treatment of lupus nephritis in lupus mice. [J]. Journal of Chongqing Medical University 46(12):1448-1453(2021) DOI： 10.13406/j.cnki.cyxb.002761.

摘要

目的：探索过表达NR4A1是否能够缓解狼疮性肾炎（lupus nephritis，LN）的肾炎症状。方法：通过腹腔注射0.5 mL pristane构建狼疮小鼠模型，分为生理盐水对照（SC）组、pristane对照（PC）组、空载体对照（VC）组及过表达NR4A1治疗（NR4A1）组。第20周尾静脉注射过表达NR4A1的脾脏单核细胞进行治疗。第28周测量小鼠踝关节左右直径。HE染色及半定量评分评估肾脏病理改变，ELISA检测血清肿瘤坏死因子-α（tumor necrosis factor α，TNF-α）及抗ds-DNA浓度。荧光定量qPCR检测脾脏NR4A1、Bcl-2基因mRNA表达。结果：与SC组相比，PC组LN相关活动指标明显升高，踝关节直径[4.69（4.26，5.14）mm，P=0.000]、抗ds-DNA抗体浓度[（173.11±25.49）ng/mL，P=0.000]、肾脏病理评分[2.78（2.68，2.81），P=0.000]和NR4A1表达（0.40±0.09，P=0.008）明显降低。与PC组、VC组相比，NR4A1组LN活动指标明显改善，踝关节直径[3.80（3.44，4.20）mm，PPC=0.002，PVC=0.033]、抗ds-DNA抗体浓度[（51.92±10.91）ng/mL，PPC=0.008，PVC=0.025]、肾脏病理评分[1.39（1.30，1.49），PPC=0.002，PVC=0.018]。ELISA结果显示NR4A1组TNF-α浓度[（542.86±108.28）pg/mL]明显低于PC组[（1 779.00±358.40）pg/mL，P=0.008]、VC组[（1 759.71±280.27）pg/mL，P=0.010]。Real-time PCR结果显示NR4A1组Bcl-2基因表达（1.92±0.58）明显高于PC组（0.48±0.20，P=0.000）。结论：过表达NR4A1缓解LN小鼠LN症状，降低肾炎活动指标，可能涉及NR4A1、TNF-α及Bcl-2之间的相互作用。

Abstract

Objective: To explore whether overexpression of NR4A1 can alleviate lupus nephritis (LN). Methods: A mouse model of LN was constructed by intraperitoneal injection of 0.5 mL pristane

divided into saline control group (SC)

pristane control group (PC)

vector control group (VC) and overexpressed NR4A1 group. At the end of 20thweek

the monocytes overexpressed NR4A1 were injected into the tail vein. The diameter of ankles was measured at the end of 28thweek. Renal pathological sections were stained with HE staining and semi-quantitative scores were used to assess renal pathological damage. Serum TNF-α and anti-ds-DNA concentrations were measured by ELISA. The expression of Bcl-2 and NR4A1 in the spleen was detected by real-time PCR. Results: The results showed that compared with the SC group

LN-related activity indicators in the PC group were significantly increased

but the ankle joint diameter[4.69 (4.26

5.13) mm

P=0.000]

the anti-ds-DNA antibody concentration [(173.11±25.49) ng/mL

P=0.000]

renal pathology score[2.78 (2.68

2.81)

P=0.000]

and the expression of NR4A1 (0.40±0.09

P=0.008) was significantly reduced. Compared with the PC and VC groups

the NR4A1 group LN activity indicators were significantly improved

the ankle joint diameter[3.80 (3.44

4.20) mm

PPC=0.002

PVC=0.033]

the concentration of anti-ds-DNA antibody [(51.92±10.91) ng/mL

PPC=0.008

PVC=0.025]

renal pathology score[1.39 (1.30

1.49)

PPC=0.002

PVC=0.018].ELISA results showed that the concentration of TNF-α in the NR4A1 group [(542.86±108.28) pg/mL]was significantly lower than that of the PC group [(1 779.00±358.40) pg/mL

P=0.008]and the VC group [(1 759.71±280.27) pg/mL

P=0.010].Real-time PCR results showed that the expression of Bcl-2 gene in the NR4A1 group (1.92±0.58) was significantly higher than that of the PC group (0.48±0.20

P=0.000). Conclusion: Overexpression of NR4A1 alleviates the symptoms of LN and reduces LN activity indicators in LN mice

which may involve the interaction among NR4A1

TNF-α and Bcl-2.

关键词

狼疮性肾炎NR4A1单核细胞凋亡肿瘤坏死因子-α

Keywords

lupus nephritisNR4A1monocyteapoptosistumor necrosis factor-α

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