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Cholestasis is a common liver disease that seriously affects liver function.
In the liver tissue of cholestasis patients and the corresponding rat experimental model, the membrane transporter MRP3 showed significantly high expression.
Oleanolic acid is not a rare substance; however, its role in cholestasis has been poorly studied.
Understanding the effects of oleanolic acid on liver damage and how it affects the expression of related proteins and genes is critical to preventing and treating cholestasis.
In the experiment, we selected 15 SD rats and divided them into three groups using a random number table. The three groups are: simulated ligation group, biliary ligation group and oleanolic acid treatment group. Each group has 5 rats.
The Sham group and the BDL group received physiological saline treatment. The BDL group also added OA. The entire treatment process lasted for 7 days.
Tissue samples are then collected for subsequent testing.
HE staining was used to detect the degree of liver damage.
Research data shows that the degree of liver damage in the BDL and OA combined treatment group has been significantly improved compared with the biliary ligation group.
In the liver sections of the rats in the Sham group, the lobular structure could be clearly seen, the cells were arranged neatly, and no cell death was observed. The tissue status of the rat livers in the BDL + OA group was also maintained in good condition. However, the livers of the rats in the BDL group were damaged, and areas of necrosis also appeared.
Using Blot technology, we were able to observe the differences in expression of Mrp3 and Lrh-1 proteins.
Experimental results showed that the expression of Mrp3 in the BDL plus OA group was 2.4 times that of the Sham group, and the expression of Lrh-1 also increased by 1.8 times.
Normally, MRP3 is either barely visible or only vaguely visible on the surface of liver cells. However, when it comes to cholestasis, especially after treatment with oleanolic acid, its visibility increases significantly.
This indicates that oleanolic acid upregulates the expression of Mrp3 protein.
RT-PCR technology was used to detect changes in the mRNA levels of the two genes Mrp3 and Lrh-1.
Real-time fluorescence quantitative PCR detection results showed that the expression level of Mrp3 in the BDL plus OA treatment group was 3.2 times that of the control group, and the expression level of Lrh-1 was 2.2 times that of the control group.
The test results showed that the protein levels were consistent with the results. We observed that at the mRNA level, the expression levels of Mrp3 and Lrh-1 in the BDL group and BDL plus OA group were higher than those in the Sham group. In addition, the difference between the BDL plus OA group and the BDL group was more obvious, and this finding was statistically significant.
Immunofluorescence staining technology has deeply verified the effect of tilearolic acid in enhancing the expression of Mrp3 on the surface of hepatocytes. This technique reveals the effect of oleanolic acid on Mrp3 expression. This effect was clearly demonstrated on the surface of liver cells.
MRP3/Mrp3 is located on the bottom membrane of liver cells and belongs to the MRPs family. It affects many targets, including bile acids, conjugated bilirubin, and a variety of drugs.
Research results show that through the action of oleanolic acid, the expression of Mrp3 protein on the surface of liver cells is significantly increased. The content of Mrp3 protein on the surface of liver cells increased significantly.
Experimental data showed that Blot and RT-PCR techniques detected that changes in the level of the transcription factor Lrh-1 were synchronized with changes in the level of Mrp3. This synchronous change suggests that oleanolic acid may regulate the expression of Mrp3 on the surface of liver cells by acting on Lrh-1, leading to an increase in its number.
Oleanolic acid helps reduce cholestasis-induced liver damage in rats. In addition, it can also increase the expression of Mrp3 and Lrh-1, which may have a positive effect on the transport and excretion of bile acids.
Whether oleanolic acid can become an effective drug in the treatment of cholestasis in future clinical applications is a question worth exploring.
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