Effect of Yipi Yanggan prescription on malignant transformation of liver stem cells in rats with liver precancerous lesion and its mechanism of action
10.3969/j.issn.1001-5256.2022.04.023
- VernacularTitle:益脾养肝方对大鼠肝癌前病变肝干细胞恶性转化的影响和作用机制
- Author:
Di JU
1
,
2
;
Mi LI
2
;
Man HAN
2
;
Bingying FANG
2
;
Shuguang YAN
2
;
Jingtao LI
3
Author Information
1. Shaanxi Key Laboratory of Integrated Traditional and Western Medicine for Prevention and Treatment of Cardiovascular Diseases, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi 712046, China
2. School of Basic Medical Sciences, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi 712046, China
3. First Department of Hepatology, The Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang, Shaanxi 712000, China
- Publication Type:Original Articles_Liver Neoplasms
- Keywords:
Liver Neoplasms;
Yipi Yanggan Recipe;
Pathologic Processes;
Precancerous Conditions
- From:
Journal of Clinical Hepatology
2022;38(4):865-871
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of Yipi Yanggan prescription on the malignant transformation of liver stem cells in liver precancerous lesion induced by diethylnitrosamine (DEN) and its possible molecular mechanism. Methods A total of 35 male Sprague-Dawley rats were randomly divided into normal control group (blank group), DEN model group (model group), DEN+Yipi Yanggan prescription group (Yipi Yanggan prescription group), and DEN+Hugan tablet group (Hugan tablet group), with 5 rats in the blank group and 10 rats in the other three groups. Intraperitoneal injection of DEN was performed to establish a model of liver precancerous lesion, the rats were sacrificed after 16 weeks of administration. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and albumin (Alb) were measured; liver tissue was collected to observe the changes in size and appearance and calculate liver weight ratio (liver index); HE staining and Sirius Red staining were used to observe the pathological and morphological changes of rat liver tissue; immunohistochemistry was used to measure the expression of OV6 and glutathione S-transferase-Pi (GST-Pi); RT-PCR was used to measure the mRNA expression of EpCAM, CD133, and CD90, and Western blot was used to measure the protein expression of PI3K, Akt, and mTOR and their phosphorylation level. A one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t -test was used for further comparison between two groups. Results Compared with the model group, the Yipi Yanggan prescription group and the Hugan tablet group had significant improvements in liver pathology and morphology, significant reductions in liver index and the levels of ALT and AST, and a significant increase in the level of Alb (all P < 0.05), as well as significant reductions in the protein expression levels of GST-Pi, OV6, p-PI3K, p-Akt, and p-mTOR and the mRNA expression levels of EpCAM, CD133, and CD90 (all P < 0.05). Compared with the Hugan tablet group, the Yipi Yanggan prescription group showed a more significant protective effect on the liver, with significant reductions in liver index and the levels of ALT and AST, and a significant increase in the level of Alb (all P < 0.05), as well as significant reductions in the protein expression levels of GST-Pi, OV6, p-PI3K, p-Akt, and p-mTOR and the mRNA expression levels of EpCAM, CD133, and CD90 (all P < 0.05). Conclusion Yipi Yanggan prescription can improve liver precancerous lesion induced by DEN in rats by inhibiting the malignant transformation of liver stem cells, and its mechanism of action may be associated with the PI3K/Akt/mTOR signaling pathway.
