Mechanism of Hedysari Radix Polysaccharide on Diabetic Nephropathy in db/db Mice Based on JAK2/STAT3 Signaling Pathway

CHEN Yanxu; JIN Zhisheng; JIANG Xiaoxue; ZHANG Boling; FU Yaoqin; JIN Caiyun; ZHANG Qinyuan; XU Changqing

doi:10.13422/j.cnki.syfjx.20230106

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Mechanism of Hedysari Radix Polysaccharide on Diabetic Nephropathy in db/db Mice Based on JAK2/STAT3 Signaling Pathway

更新时间：2023-06-02

- Mechanism of Hedysari Radix Polysaccharide on Diabetic Nephropathy in db/db Mice Based on JAK2/STAT3 Signaling Pathway
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 29, Issue 13, Pages: 65-71(2023)
- 作者机构：
  
  1.甘肃中医药大学，兰州 730030
  2.甘肃中医药大学附属医院，兰州 730030
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20230106
  CLC： R2-0;R22;R285.5;R289;R33
- Published：05 July 2023，
  
  Published Online：29 November 2022，
  
  Received：19 September 2022，
- 稿件说明：
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陈彦旭,金智生,姜晓雪等.基于JAK2/STAT3信号通路探讨红芪多糖对糖尿病肾病db/db小鼠作用机制[J].中国实验方剂学杂志,2023,29(13):65-71.

CHEN Yanxu,JIN Zhisheng,JIANG Xiaoxue,et al.Mechanism of Hedysari Radix Polysaccharide on Diabetic Nephropathy in db/db Mice Based on JAK2/STAT3 Signaling Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(13):65-71.
陈彦旭,金智生,姜晓雪等.基于JAK2/STAT3信号通路探讨红芪多糖对糖尿病肾病db/db小鼠作用机制[J].中国实验方剂学杂志,2023,29(13):65-71. DOI： 10.13422/j.cnki.syfjx.20230106.

CHEN Yanxu,JIN Zhisheng,JIANG Xiaoxue,et al.Mechanism of Hedysari Radix Polysaccharide on Diabetic Nephropathy in db/db Mice Based on JAK2/STAT3 Signaling Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(13):65-71. DOI： 10.13422/j.cnki.syfjx.20230106.

摘要

目的

观察红芪多糖对糖尿病肾病db/db小鼠Janus激酶2（JAK2）/信号转导及转录激活因子3（STAT3）信号通路的影响。

方法

将50只db/db小鼠按体质量随机分为模型组、厄贝沙坦组、红芪多糖高、中、低剂量组，每组10只；另取10只C57BL/6小鼠作为正常组。正常组和模型组给予5 mL·kg

-1

蒸馏水，厄贝沙坦组给予22.75 mg·kg

-1

厄贝沙坦悬溶液，红芪多糖高、中、低剂量组分别给予200、100、50 mg·kg

-1

红芪多糖悬溶液，6组小鼠每日灌胃1次，连续给药12周。检测各组小鼠尿酸（UA）、甘油三酯（TG）、总胆固醇（TC），过碘酸雪夫反应（PAS）、马松（Masson）染色观察肾脏组织病理变化，蛋白免疫印迹法（Western blot）、实时荧光定量聚合酶链式反应（Real-time PCR）检测肾脏中JAK2、STAT3、细胞信号转导抑制因子3（SOCS3）及肿瘤坏死因子-

（TNF-

）蛋白及mRNA的表达水平。

结果

治疗12周后，与正常组比较，模型组小鼠肾脏组织病理超微结构病变显著，其UA、TG、TC水平均显著升高（

0.01）；与模型组比较，红芪多糖高、中剂量及厄贝沙坦组小鼠肾脏组织病理超微结构均得到一定程度改善，且UA、TG、TC水平均明显降低（

0.05，

0.01）；与正常组比较，模型组SOCS3蛋白及mRNA表达水平下降，JAK2、STAT3、TNF-

蛋白及mRNA表达水平显著升高（

0.01）；与模型组比较，红芪多糖高、中剂量及厄贝沙坦组SOCS3蛋白及mRNA表达水平升高，JAK2、STAT3、TNF-

蛋白及mRNA表达水平明显降低（

0.05，

0.01）。

结论

红芪多糖可在一定程度上减轻糖尿病肾病的肾损伤，其机制可能与抑制JAK2/STAT3信号通路激活有关。

Abstract

Objective

To observe the effect of Hedysari Radix polysaccharide （HRP） on the Janus kinase 2 （JAK2）/signal transducer and activator of transcription protein 3 （STAT3） signaling pathway in diabetic nephropathy db/db mice.

Method

Fifty db/db mice were randomly divided into model group， irbesartan group （irbesartan suspension， 22.75 mg·kg

-1

）， and high-， medium-， and low-dose HRP groups （HRP suspension， 200， 100， 50 mg·kg

-1

） according to the body weight， with 10 mice in each group. Another 10 C57BL/6 mice were assigned to the normal group. The mice were treated with corresponding drugs by gavage， while those in the normal group and the model group received distilled water at 5 mL·kg

-1

. The mice in the six groups were administered once a day by gavage for 12 consecutive weeks. The uric acid （UA）， triglycerides （TG）， and total cholesterol （TC） were detected. Periodic acid-Schiff （PAS） staining and Masson staining were used to observe the pathological changes in kidney tissues. Western blot and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） were used to detect the protein and mRNA expression levels of JAK2， STAT3， suppressor of cytokine signaling 3 （SOCS3）， and tumor necrosis factor-

（TNF-

） in the kidney.

Result

After 12 weeks of treatment， compared with the normal group， the model group showed significant pathological ultrastructural changes in kidney tissues and increased UA， TG， and TC levels （

0.01）. Compared with the model group， the high- and medium-dose HRP groups and the irbesartan group showed improvement in pathological ultrastructure of kidney tissues and reduced UA， TG， and TC levels （

0.05，

0.01）. Compared with the normal group， the model group showed a decrease in SOCS3 protein and mRNA expression levels and an increase in JAK2， STAT3， and TNF-

protein and mRNA expression levels （

0.01）. Compared with the model group， the high- and medium-dose HRP groups and the irbesartan group showed an increase in SOCS3 protein and mRNA expression levels and a decrease in JAK2， STAT3， and TNF-

protein and mRNA expression levels （

0.05，

0.01）.

Conclusion

HRP can alleviate renal damage in diabetic nephropathy to a certain extent， and its mechanism may be related to the inhibition of the activation of the JAK2/STAT3 signaling pathway.

关键词

红芪多糖糖尿病肾病Janus激酶2（JAK2）信号转导及转录激活因子3（STAT3）细胞信号转导抑制因子3（SOCS3）肿瘤坏死因子-α（TNF-α）

Keywords

Hedysari Radix polysaccharidediabetic nephropathyJanus kinase 2 （JAK2）signal transducer and activator of transcription protein 3 （STAT3）suppressor of cytokine signaling 3 （SOCS3）tumor necrosis factor-α （TNF-α）

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