Research on Therapeutic Mechanism of Canhuang Tablets on Jaundiced Rats Induced by ANIT

Ba-tu JIRIMU; Guo-ming XIE; Na FAN; Yan-ping ZHOU; Jin HAN

doi:10.13422/j.cnki.syfjx.20201050

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Research on Therapeutic Mechanism of Canhuang Tablets on Jaundiced Rats Induced by ANIT

Pharmacology | 更新时间：2020-09-09

- Research on Therapeutic Mechanism of Canhuang Tablets on Jaundiced Rats Induced by ANIT
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 26, Issue 17, Pages: 64-69(2020)
- 作者机构：
  
  1.内蒙古医科大学蒙医药研究院，呼和浩特 010110
  2.中国人民解放军总医院第五医学中心，北京 100039
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20201050
  CLC： R22;R256;R28;R96;C37
- Published Online：04 February 2020，
  
  Published：05 September 2020
- 稿件说明：
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吉日木巴图,谢国明,范娜等.残黄片对ANIT诱导黄疸模型大鼠的退黄作用机制分析[J].中国实验方剂学杂志,2020,26(17):64-69.

JIRIMU Ba-tu,XIE Guo-ming,FAN Na,et al.Research on Therapeutic Mechanism of Canhuang Tablets on Jaundiced Rats Induced by ANIT[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(17):64-69.
吉日木巴图,谢国明,范娜等.残黄片对ANIT诱导黄疸模型大鼠的退黄作用机制分析[J].中国实验方剂学杂志,2020,26(17):64-69. DOI： 10.13422/j.cnki.syfjx.20201050.

JIRIMU Ba-tu,XIE Guo-ming,FAN Na,et al.Research on Therapeutic Mechanism of Canhuang Tablets on Jaundiced Rats Induced by ANIT[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(17):64-69. DOI： 10.13422/j.cnki.syfjx.20201050.

摘要

目的

考察残黄片对

-萘异硫氰酸酯（ANIT）诱导黄疸模型大鼠肝脏法尼醇X受体（FXR），尿苷二磷酸葡萄糖醛酸转移酶1A1（UGT1A1）和多药耐药相关蛋白2（MRP2）mRNA和蛋白表达的影响，探讨其治疗残留黄疸的作用机制。

方法

大鼠分为正常组、模型组、残黄片（CHP）组和熊去氧胆酸片（UDCA）组，ANIT灌胃复制黄疸模型，相应药物干预后进行血清总胆红素（TBIL），总胆汁酸（TBA），丙氨酸氨基转移酶（ALT），天门冬氨酸氨基转移酶（AST）和碱性磷酸酶（ALP）的含量检测和肝组织病理学检查，以评价残黄片的治疗作用。应用逆转录-聚合酶链式反应（RT-PCR）和蛋白质免疫印迹试验（Western blot）检测各组大鼠肝组织FXR，UGT1A1，MRP2 mRNA和蛋白的相对表达量。

结果

CHP能显著降低由ANIT引起的大鼠血清TBIL，TBA，ALT，AST，ALP的升高，抑制肝脏病理学改变，退黄作用优于UDCA。与正常组比较，ANIT造模后显著抑制大鼠肝组织FXR，UGT1A1，MRP2的mRNA水平（

0.01）。与模型组比较，CHP和UDCA干预后均显著提升了各蛋白目的基因mRNA水平（

0.01），在提升胆红素代谢酶UGT1A1的mRNA水平上CHP优于UDCA（

0.01）。在影响蛋白表达方面，与正常组比较ANIT造模使大鼠FXR表达明显升高（

0.05），CHP干预有促进FXR表达的趋势，而UDCA未见有促进趋势，但二者无显著差异。在促进胆红素代谢和胆汁排泄方面，ANIT造模使得UGT1A1，MRP2的表达显著降低（

0.01），而CHP治疗后显著提高了UGT1A1和MRP2蛋白的表达（

0.01）。在提高胆红素与胆汁酸外排蛋白MRP2的表达上CHP优于UDCA（

0.01）。

结论

CHP退黄作用机制与激活肝脏FXR mRNA的表达，促进胆红素代谢酶UGT1A1和胆汁酸转运体MRP2的mRNA和蛋白表达，提高肝脏对游离胆红素的代谢并促进胆汁酸排出肝脏，缓解胆汁淤积性肝损伤有关。

Abstract

Objective

To explore the therapeutic mechanism of Canhuang tablets on the mRNA and protein expression of farnesoid X receptor (FXR)

uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) and multidrug resistance associated protein 2 (MRP2) in the liver of jaundiced rats induced by

-naphthalene isothiocyanate (ANIT).

Method

The rats were divided into normal group

model group

Canhuang tablets (CHP) group and ursodeoxycholic acid tablets (UDCA) group. The jaundice model was reproduced by ANIT. After the intervention of the corresponding drugs

the contents of total bilirubin (TBIL)

total bile acid (TBA)

alanine aminotransferase (ALT)

aspartate aminotransferase (AST) and alkaline phosphatase (ALP) in serum and the liver histopathology were examined to evaluate the therapeutic effect of CHP. The relative mRNA and protein expressions of FXR

UGT1A1 and MRP2 in rat liver tissues were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot.

Result

CHP can significantly reduce the increase of TBIL

TBA

ALT

AST and ALP caused by ANIT in rat serum

and inhibit the liver pathological changes

which showed that the removing jaundice effect of CHP was better than UDCA. Compared with the normal group

ANIT significantly inhibited the mRNA levels of FXR

UGT1A1 and MRP2 in rat liver tissues after modeling (

0.01). Compared with the model group

CHP and UDCA significantly increased the mRNA levels of target genes of each protein after intervention (

0.01)

and CHP was superior to UDCA in improving the mRNA level of bilirubin metabolizing enzyme UGT1A1 (

0.01). In the aspect of affecting protein expression

compared with the normal group

ANIT modeling significantly increased the expression of FXR in rats (

0.05). CHP intervention showed a tendency to promote the expression of FXR

while UDCA did not

but there was no significant difference between them. In the aspects of promoting bilirubin metabolism and bile excretion

the expressions of UGT1A1 and MRP2 were significantly decreased by ANIT modeling (

0.01)

while the expressions of UGT1A1 and MRP2 proteins were significantly increased after treatment of CHP (

0.01). CHP was superior to UDCA in increasing the expression of bilirubin and bile acid efflux protein MRP2 (

0.01).

Conclusion

The jaundice abating mechanism of CHP is related to activating FXR mRNA expression in liver

promoting the mRNA and protein expression of bilirubin metabolizing enzyme UGT1A1 and bile acid transporter MRP2

improving liver metabolism of free bilirubin and promoting bile acid excretion from the liver

and alleviating cholestatic liver injury.

关键词

Keywords

references

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Related Institution

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