Effect of Wenshen Yisui Shengxue Prescription on BMP/Smad Signaling Pathway in Liver of RA Rats

ZHANG Zi-yan; ZHANG Xin-xue; YANG Mei-juan; HUANG Ya-wei; WANG Ting; SONG Lu-xia; ZHAO Zong-jiang

doi:10.13422/j.cnki.syfjx.20181620

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Effect of Wenshen Yisui Shengxue Prescription on BMP/Smad Signaling Pathway in Liver of RA Rats

更新时间：2024-01-04

- Effect of Wenshen Yisui Shengxue Prescription on BMP/Smad Signaling Pathway in Liver of RA Rats
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 24, Issue 16, Pages: 88-95(2018)
- 作者机构：
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20181620
  CLC： R285.5
- Published：2018
- 稿件说明：
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ZHANG Zi-yan, ZHANG Xin-xue, YANG Mei-juan, et al. Effect of Wenshen Yisui Shengxue Prescription on BMP/Smad Signaling Pathway in Liver of RA Rats[J]. Chinese journal of experimental traditional medical formulae, 2018, 24(16): 88-95.
DOI：

ZHANG Zi-yan, ZHANG Xin-xue, YANG Mei-juan, et al. Effect of Wenshen Yisui Shengxue Prescription on BMP/Smad Signaling Pathway in Liver of RA Rats[J]. Chinese journal of experimental traditional medical formulae, 2018, 24(16): 88-95. DOI： 10.13422/j.cnki.syfjx.20181620.

摘要

目的：探讨温肾益髓生血方对RA大鼠贫血的改善作用及其骨形成蛋白（bone morphogenetic protein，BMP）/Smad信号通路的影响。方法： 42只雄性SPF级Wister大鼠，根据体质量分层随机分组2次，即正常组、假手术组、模型组、尿毒清（2.33 g·kg-1）组、温肾益髓生血（3.5 g·kg-1）组。模型组和治疗组上午180 mg·kg-1·d-1腺嘌呤灌胃，下午治疗组给予相应的治疗药物，正常组、假手术组和模型组给予等体积的去离子水灌胃，每周称量大鼠体质量，治疗12周后，各组大鼠麻醉后取血，分离血清，检测肌酐（SCr），尿素氮（BUN），尿酸（UA）；全血测红细胞（RBC），血红蛋白（HGB）；取材固定肾组织、肝脏组织，苏木素-伊红（HE）染色观察大鼠肾脏病理，免疫组化及原位杂交技术检测大鼠肝脏BMP6，Smad4，Smad1/5/8，p-Smad1/5/8，铁调素（hepcidin） mRNA及蛋白表达水平。结果：与正常组及假手术组比较，模型组体质量明显降低（P<0.01），血清BUN，SCr水平明显升高（P<0.01），肾脏病理损害明显；与模型组比较，温肾益髓生血组大鼠一般状态明显改善，血RBC，HGB水平升高（P<0.01），与正常组和假手术组比较，模型组大鼠肝脏高表达BMP6，Smad4，Smad1/5/8，hepcidin（P<0.01）；与模型组比较，温肾益髓生血组BMP6，Smad4，Smad1/5/8，p-Smad1/5/8，hepcidin蛋白表达水平显著降低（P<0.01）。结论：温肾益髓生血方对RA大鼠贫血具有一定的改善作用，可能是通过干预肝脏BMP/Smad信号通路实现的。

Abstract

Objective: To explore the effect of Wenshen Yisui Shengxue prescription on anemia in RA rats and bone morphogenetic protein(BMP)/Smad signaling pathway in liver. Method: A total of 42 male SPF grade Wister rats were randomly divided into groups twice according to the body mass stratification:normal group

sham operation group

model group

uremia(2.33 g·kg-1) group and Wenshen Yisui Shengxue(3.5 g·kg-1) group. In the model group and the treatment group

180 mg·kg-1·d-1 adenine was given by gavage in the morning

and the treatment group was treated with the corresponding medicine in the afternoon. The normal group

the sham operation group and the model group were given the equal volume of deionized water. After 12 weeks of treatment

blood and serum were collected after the rats were anesthesia. SCr and urea nitrogen (BUN)

uric acid (UA)

whole blood test red cell (RBC)

hemoglobin (HGB) were detected; kidney tissue and liver tissue were fixed; hematoxylin-eosin(HE) staining was used to observe kidney pathology; immunohistochemistry and in situ hybridization technique were used to detect bone morphogenetic protein 6 (BMP6)

Smad4

Smad1/5/8

p-Smad1/5/8

hepcidin (hepcidin) mRNA and protein expressions in rat liver. Result: Compared with normal group and sham operation group

the body mass of the model group decreased obviously (P<0.01)

the levels of serum BUN and SCr increased obviously (P<0.01)

and the pathological damage of kidney was obvious. Compared with model group

the general state of the Wenshen Yisui Shengxue group was obviously improved

and the levels of blood RBC and HGB were increased (P<0.01); compared with the normal group and the sham operation group

the model group showed high expressions of BMP6

Smad4

Smad1/5/8 and hepcidin in liver (P<0.01). Compared with the model group

BMP6

Smad4

Smad1/5/8

p-Smad1/5/8 and hepcidin protein expressions in the Wenshen Yisui Shengxue group were significantly reduced (P<0.01). Conclusion: Wenshen Yisui Shengxue prescription has a certain effect in alliviating anemia in RA rats

which may be realized by intervening BMP/Smad signaling pathway in liver.

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