白芍总苷调节TLR9/MyD88/NF-<italic style="font-style: italic">κ</italic>B通路改善系统性红斑狼疮小鼠肾脏损伤

吴琼; 于红红; 罗瑞熙; 何金涛; 罗舒文; 俞琦

doi:10.13422/j.cnki.syfjx.20221239

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白芍总苷调节TLR9/MyD88/NF-κB通路改善系统性红斑狼疮小鼠肾脏损伤

药理 | 更新时间：2022-05-18

- 白芍总苷调节TLR9/MyD88/NF-κB通路改善系统性红斑狼疮小鼠肾脏损伤
- Total Glucosides of Paeony Improve Renal Injury in Mice with Systemic Lupus Erythematosus by Regulating TLR9/MyD88/NF-κB Pathway
- 中国实验方剂学杂志 2022年28卷第12期页码：103-110
- 作者机构：
  
  贵州中医药大学，贵阳 550025
- 作者简介：
  
  吴琼，在读硕士，从事中西医结合基础研究，E-mail：1058851811@qq.com
  俞琦，博士，教授，硕士生导师，从事中西医结合基础研究，E-mail：756128099@qq.com
- 基金信息：
  
  贵州省中医药、民族医药科学技术研究课题项目(QZYY-2016-002)
- DOI：10.13422/j.cnki.syfjx.20221239
  中图分类号： R2-0;R33;R289;R392.3
- 纸质出版日期：2022-06-20，
  
  网络出版日期：2022-04-07，
  
  收稿日期：2021-12-14，
- 稿件说明：
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吴琼,于红红,罗瑞熙等.白芍总苷调节TLR9/MyD88/NF-κB通路改善系统性红斑狼疮小鼠肾脏损伤[J].中国实验方剂学杂志,2022,28(12):103-110.

WU Qiong,YU Hong-hong,LUO Rui-xi,et al.Total Glucosides of Paeony Improve Renal Injury in Mice with Systemic Lupus Erythematosus by Regulating TLR9/MyD88/NF-κB Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(12):103-110.
吴琼,于红红,罗瑞熙等.白芍总苷调节TLR9/MyD88/NF-κB通路改善系统性红斑狼疮小鼠肾脏损伤[J].中国实验方剂学杂志,2022,28(12):103-110. DOI： 10.13422/j.cnki.syfjx.20221239.

WU Qiong,YU Hong-hong,LUO Rui-xi,et al.Total Glucosides of Paeony Improve Renal Injury in Mice with Systemic Lupus Erythematosus by Regulating TLR9/MyD88/NF-κB Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(12):103-110. DOI： 10.13422/j.cnki.syfjx.20221239.

摘要

目的

基于Toll样受体9/髓样分化因子88/核转录因子-

B（TLR9/MyD88/NF-

B）信号通路研究白芍总苷（TGP）对MRL/lpr狼疮模型小鼠肾脏损伤的干预作用，探讨TGP防治系统性红斑狼疮（SLE）的部分免疫学机制。

方法

将SPF级MRL/lpr雌性小鼠随机分为4组，模型组、地塞米松组（0.15 g·kg

-1

）、TGP高、低剂量组（0.078、0.039 g·kg

-1

），雌性C57BL/6J小鼠设为空白组，每组7只；各组小鼠每天同一时间段给予相应药物或生理盐水灌胃。4周后采集标本，称取肾脏、脾脏质量，计算脏器指数；生化分析法检测各组血清肌酐（SCr）、血尿素氮（BUN）水平；苏木素-伊红（HE）染色观察小鼠肾脏组织病理学变化；马松（Masson）染色评估小鼠肾脏组织纤维化程度；酶联免疫吸附测定法（ELISA）检测血清白细胞介素（IL）-2、干扰素-

（IFN-

）、IL-4和抗核抗体（ANA）的水平；实时荧光定量聚合酶链式反应（Real-time PCR）检测肾组织中TLR9、MyD88、NF-

B p65的mRNA表达；免疫荧光法检测肾组织中TLR9、NF-

B p65蛋白表达；蛋白免疫印迹法（Western blot）检测肾、脾组织中TLR9、MyD88、NF-

B p65蛋白的表达水平。

结果

与空白组比较，模型组小鼠SCr、BUN及脾脏指数和肾脏指数明显升高（

0.05），肾组织病理损伤和纤维化程度明显增强；血清IFN-

、IL-4及ANA水平显著升高，IL-2水平明显降低（

0.05）；肾脏和脾脏中TLR9、MyD88及NF-

B p65的mRNA和蛋白水平明显升高（

0.05）。与模型组比较，TGP高、低剂量组小鼠SCr、BUN及脾脏指数和肾脏指数明显降低（

0.05），肾组织病理损伤和纤维化程度明显减轻；血清IFN-

、IL-4及ANA水平明显下降（

0.05），IL-2水平明显升高；肾脏和脾脏组织中TLR9、MyD88和NF-

B p65等分子mRNA和蛋白表达水平均明显降低（

0.05）。

结论

TGP可能通过调控TLR9/MyD88/NF-

B信号通路，进而抑制其下游相关炎症因子表达，发挥免疫调节及抗SLE肾脏损伤作用。

Abstract

Objective

To investigate the intervention effect of total glucosides of paeony （TGP） on the renal injury of MRL/lpr mice based on the Toll-like receptor 9 （TLR9）/myeloid differentiation factor 88 （MyD88）/nuclear transcription factor-

B （NF-

B） signaling pathway and explore the immunological mechanism of TGP in preventing and treating systemic lupus erythematosus （SLE）.

Method

MRL/lpr female mice of SPF grade were randomly divided into a model group， a dexamethasone group （0.15 g·kg

-1

）， and high- （0.078 g·kg

-1

） and low-dose （0.039 g·kg

-1

） TGP groups， and female C57BL/6J mice were assigned to a blank group， with 7 mice in each group. Mice in each group were treated with corresponding drugs or normal saline by gavage at the same time every day. After 4 weeks， samples were collected. The kidney and spleen were weighed， and the organ index was calculated. Serum creatinine （SCr） and blood urea nitrogen （BUN） levels in each group were detected by biochemical assay. Hematoxylin-eosin （HE） staining was used to observe the histopathological changes in the kidney. The degree of renal fibrosis was evaluated by Masson staining. The serum levels of interleukin （IL）-2， interferon （IFN）-

， IL-4， and anti-nuclear antibody （ANA） were detected by enzyme-linked immunosorbent assay （ELISA）. The mRNA expression of TLR9， MyD88， and NF-

B p65 in renal tissues was detected by real-time quantitative polymerase chain reaction （Real-time PCR）. The protein expression of TLR9 and NF-

B p65 in renal tissues was detected by immunofluorescence. The protein expression of TLR9， MyD88， and NF-

B p65 in renal and spleen tissues was tested by Western blot.

Result

Compared with the blank group， the model group showed increased SCr， BUN， spleen index， and kidney index （

0.05）， deteriorated pathological injury and fibrosis in renal tissues， elevated serum levels of IFN-

， IL-4， and ANA， decreased level of IL-2 （

0.05）， and up-regulated TLR9， MyD88， and NF-

B p65 mRNA and protein levels in the kidney and spleen （

0.05）. Compared with the model group， the TGP groups displayed reduced SCr， BUN， spleen index， and kidney index （

0.05）， relieved pathological damage and fibrosis in renal tissues， decreased serum levels of IFN-

， IL-4， and ANA （

0.05）， increased level of IL-2， and declining mRNA and protein expression levels of TLR9， MyD88， and NF-

B p65 in the kidney and spleen （

0.05）.

Conclusion

TGP may inhibit the expression of downstream inflammatory factors to regulate immunity and resist SLE-induced renal injury by regulating the TLR9/MyD88/NF-

B signaling pathway.

关键词

白芍总苷系统性红斑狼疮（SLE）Toll样受体9/髓样分化因子88/核转录因子-κB（TLR9/MyD88/NF-κB）SLE模型小鼠

Keywords

total glucosides of paeonysystemic lupus erythematosus（SLE）Toll-like receptor 9 （TLR9）/myeloid differentiation factor 88 （MyD88）/nuclear transcription factor-κB （NF-κB） signaling pathwaySLE model mice

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白芍总苷调节TLR9/MyD88/NF-κB通路改善系统性红斑狼疮小鼠肾脏损伤

Total Glucosides of Paeony Improve Renal Injury in Mice with Systemic Lupus Erythematosus by Regulating TLR9/MyD88/NF-κB Pathway

DOI：10.13422/j.cnki.syfjx.20221239

摘要

Abstract

关键词

Keywords

references