Effect of <italic style="font-style: italic">Langchuangding </italic>（狼疮定） Combined with Prednisone on Renal Lipid Metabolism in MRL/lpr Mice based on Lipidomics

Kaili WANG; Xiaofen XU; Qiao DUAN; Lu LU; Changfeng HU; Jida ZHANG

doi:10.13288/j.11-2166/r.2022.10.015

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Effect of Langchuangding （狼疮定） Combined with Prednisone on Renal Lipid Metabolism in MRL/lpr Mice based on Lipidomics

更新时间：2022-05-11

- Effect of Langchuangding （狼疮定） Combined with Prednisone on Renal Lipid Metabolism in MRL/lpr Mice based on Lipidomics
- Journal of Traditional Chinese Medicine Vol. 63, Issue 10, Pages: 976-982(2022)
- 作者机构：
  
  1.浙江中医药大学基础医学院，浙江省杭州市滨江区滨文路548号，310053
  2.浙江中医药大学附属第三医院
- 作者简介：
- 基金信息：
- DOI：10.13288/j.11-2166/r.2022.10.015
  CLC：
- Received：04 August 2021，
  
  Revised：2022-02-28，
  
  Published：17 May 2022
- 稿件说明：
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王凯丽,许小芬,段巧等.基于脂质组学探讨狼疮定联合泼尼松对MRL/lpr狼疮鼠肾脏脂质代谢的影响[J].中医杂志,2022,63(10):976-982.

WANG Kaili,XU Xiaofen,DUAN Qiao,et al.Effect of Langchuangding （狼疮定） Combined with Prednisone on Renal Lipid Metabolism in MRL/lpr Mice based on Lipidomics[J].Journal of Traditional Chinese Medicine,2022,63(10):976-982.
王凯丽,许小芬,段巧等.基于脂质组学探讨狼疮定联合泼尼松对MRL/lpr狼疮鼠肾脏脂质代谢的影响[J].中医杂志,2022,63(10):976-982. DOI： 10.13288/j.11-2166/r.2022.10.015.

WANG Kaili,XU Xiaofen,DUAN Qiao,et al.Effect of Langchuangding （狼疮定） Combined with Prednisone on Renal Lipid Metabolism in MRL/lpr Mice based on Lipidomics[J].Journal of Traditional Chinese Medicine,2022,63(10):976-982. DOI： 10.13288/j.11-2166/r.2022.10.015.

摘要

目的

探讨狼疮定联合泼尼松治疗狼疮性肾炎（LN）的可能作用机制。

方法

30只雌性MRL/lpr狼疮小鼠随机分为模型组、激素组和狼疮定联合激素组各10只，10只同周龄雌性MRL/MPJ小鼠作为正常组。狼疮定联合激素组予泼尼松悬液5 mg/（kg·d）和狼疮定水煎剂20 g/（kg·d）各0.1 ml灌胃，激素组予泼尼松悬液5 mg/（kg·d）和生理盐水各0.1 ml灌胃，模型组和正常组予0.2 ml生理盐水灌胃。干预2周和8周观察各组小鼠肾脏组织补体C3和IgG的沉积情况；利用多维质谱“鸟枪法”脂质组学技术（MDMS-SL）对各组小鼠肾组织中各类脂质分子［磷脂类：包括磷脂酰丝氨酸（PS）、溶血磷脂酰乙醇胺（LPE）；鞘脂类：包括鞘磷脂（SM）、硫苷脂（ST）；4-羟基烯醛类：包括4-羟基己烯醛（HHE）、4-羟基烯丙烯醛（HNDE）、4-羟基壬烯醛（HNE）、4-羟基十二碳三烯醛（HNTE）］进行分析，比较各组脂质分子含量。

结果

与正常组比较，模型组干预2周、8周小鼠肾脏中PS、SM含量降低（

＜0.01），LPE、4-羟基烯醛类总量增高（

＜0.01），小鼠肾脏干预2周未出现明显补体C3和IgG沉积，小鼠肾组织HHE、HNDE、HNE、HNTE含量及总量升高，干预8周出现明显免疫复合物补体C3和IgG沉积，肾组织HHE、HNE含量及总量升高，ST含量降低（

＜0.01）。与模型组相比，干预2周、8周狼疮定联合激素组小鼠PS、SM含量升高（

＜0.05或

＜0.01），干预2周激素组及狼疮定联合激素组小鼠免疫复合物补体C3、IgG无明显变化，小鼠ST含量降低，激素组小鼠HNDE、HNE、HNTE含量及4-羟基烯醛类总量降低（

＜0.05或

＜0.01），干预8周激素组及狼疮定联合激素组小鼠免疫复合物补体C3和IgG沉积情况明显减少，激素组HHE、SM含量升高，狼疮定联合激素组小鼠HHE、HNE含量及4-羟基烯醛类总量降低，狼疮定联合激素组LPE、4-羟基烯醛类总量降低（

＜0.05或

＜0.01）。与激素组相比，狼疮定联合激素组干预2周SM含量、4-羟基烯醛总量及各种子类含量升高，干预8周免疫复合物沉积减少更明显，PS含量、4-羟基烯醛总量及各种子类含量上调，LPE、4-羟基烯醛类总量降低（

＜0.05或

＜0.01）。

结论

肾脏脂质代谢紊乱在LN发病前就已发生，并且随着病情的进展进一步加重；狼疮定联合激素可能通过调节肾脏脂质代谢紊乱从而改善LN。

Abstract

Objective

To explore the possible mechanism of

Langchuangding

（狼疮定） combined with prednisone in the treatment of lupus nephritis （LN）.

Methods

Thirty female MRL/lpr LN mice were randomly divided into the model group （10 mice）， the hormones group （10 mice） and the combined group of

Langchuangding

and hormones （10 mice）， and 10 MRL/MPJ female mice at the same week age were set as normal control group. Prednisone suspension （5 mg/（kg·d）） and

Langchuangding

aqueous decoction （20 g/（kg·d）） each at a dosage of 0.1 ml were given by gavage in the combined group， and prednisone suspension （5 mg/（kg·d）） and normal saline each at a dosage of 0.1 ml were by gavage in the hormone group； in the model and control groups， 0.2 ml normal saline was given by gavage. The deposition of complement C3 and IgG in kidney tissue of mice were detected after 2w- and 8w-intervention. Multidimensional mass spectrometry-based shotgun lipidomics （MDMS-SL） was used to quantify and target various lipid molecules in the kidney tissue including phospholipids such as phosphatidylserine （PS） and lysophosphatidylethanolamine （LPE）， sphingolipids such as sphingomyelin （SM） and sulfatide （ST）， 4-hydroxyalkenals such as 4-hydroxyhexenal （HHE）， 4-hydroxyene acrolein （HNDE）， 4-hydroxynonanal Alkenal （HNE） and 4-hydroxydodecatrienal （HNTE）， and to compare the lipid molecule contents of each group.

Results

Compared to those in the normal group， the content of PS and SM in the kidneys in the model group significantly decreased （

＜0.01）， while total amount of LPE and 4-hydroxyalkenals increased （

＜0.01） after 2w- and 8w-intervention； there was no obvious deposition of complement C3 and IgG， but the contents and total amount of HHE， HNDE， HNE， and HNTE increased after 2w-intervention； obvious deposition of immune complex complement C3 and IgG occurred， while the content and total amount of HHE and HNE increased， and the content of ST decreased after 8w-intervention （

＜0.01）. Compared to those in the model group， the content of PS and SM in the combined group significantly increased after 2w- and 8w-intervention （

＜0.05 or

＜0.01）； after 2w-intervention， there was no significant change in the immune complex complement C3 and Ig and decreased ST content in the hormone group and the combined group， and the contents of HNDE， HNE， HNTE and the total amount of 4-hydroxyalkenals in the hormone group decreased （

＜0.05 or

＜0.01）； after 8w-intervention， the deposition of immune complexes complement C3 and IgG was significantly reduced in the hormone group and the combined group， while the content of HHE and SM increased in the hormone group； the content of HHE， HNE and the total amount of 4-hydroxyalkenals， as well as the total amount of LPE and 4-hydroxyalkenal decreased in the combined group （

＜0.05 or

＜0.01）. Compared with those in the hormone group， the content of SM， the total amount of 4-hydroxyenal and the content of various subtypes increased after 2w-intervention， while the deposition of immune complexes decreased more， and the content of PS， the total amount of 4-hydroxyalkenal and the contents of various subtypes increased， with decreased total amount of LPE and 4-hydroxyalkenal after 8w-intervention （

＜0.05 or

＜0.01）.

Conclusion

The disorder of renal lipid metabolism occurs before the onset of LN and becomes worsen with the progression of the disease.

Langchuangding

in combination with hormone has the function of regulating renal lipid metabolism disorder and thus delaying the progression of LN.

关键词

Keywords

references

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⁰

Effect of Langchuangding （狼疮定） Combined with Prednisone on Renal Lipid Metabolism in MRL/lpr Mice based on Lipidomics

DOI：10.13288/j.11-2166/r.2022.10.015

摘要

Abstract

关键词

Keywords

references