Objective

2

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

α

-naphthalene isothiocyanate (ANIT).

Method

2

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

2

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 (

P

<

0.01). Compared with the model group

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

P

<

0.01)

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

P

<

0.01). In the aspect of affecting protein expression

compared with the normal group

ANIT modeling significantly increased the expression of FXR in rats (

P

<

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 (

P

<

0.01)

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

P

<

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

P

<

0.01).

Conclusion

2

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.