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. 2022 Jan 6:2022:8644356.
doi: 10.1155/2022/8644356. eCollection 2022.

Effects and Mechanism of Oxymatrine Combined with Compound Yinchen Granules on the Apoptosis of Hepatocytes through the Akt/FoxO3a/Bim Pathway

Xian Zhang  1   2 , Jiajia Ge  1 , Xuejuan Zhu  1 , Haifeng Zhang  2 , Yuanzi Wang  1 , Tongtong Xu  1 , Wei Jiang  1 , Bin Zhang  2
Affiliations

Effects and Mechanism of Oxymatrine Combined with Compound Yinchen Granules on the Apoptosis of Hepatocytes through the Akt/FoxO3a/Bim Pathway

Xian Zhang et al. Biomed Res Int. .

Abstract

The aim of the present study was to investigate the effects and mechanism of oxymatrine (OMT) combined with compound yinchen granules (CYG) on the apoptosis of hepatocytes through the Akt/FoxO3a/Bim pathway in rats with acute liver failure. The rat model of acute liver failure was established using lipopolysaccharide/D-galactosamine (LPS/D-GalN). The expression of proteins in rat liver tissues was detected by western blot analysis. The mRNA expression of FoxO3a, Bim, Bax, Bcl-2, and caspase-3 in rat liver tissues was detected by RT-qPCR. The apoptosis rate of rat hepatocytes was determined by flow cytometry. Western blots showed that when compared with the normal group, the expression of p-Akt and p-FoxO3a in the model group was decreased (P < 0.05), while the expression of Bim was increased (P < 0.01). Compared with the model group, the expression of p-Akt and p-FoxO3a in the OMT group and the OMT combined with CYG groups was increased (P < 0.05 or P < 0.01), while the expression of Bim was decreased (P < 0.05). The Bax/Bcl-2 ratio and caspase-3 protein expression in the model group were significantly higher than those in the normal group (P < 0.01). The Bax/Bcl-2 ratio and the expression of caspase-3 protein in the OMT group and the OMT combined with CYG groups were significantly lower than those in the model group (P < 0.01). The results of RT-qPCR were consistent with those of western blot. The results of flow cytometry showed that the apoptosis rate of hepatocytes in the OMT group and the OMT combined with CYG groups was significantly lower than that in the model group (P < 0.05 or P < 0.01). We concluded that LPS/D-GalN can induce apoptosis of hepatocytes in rats with acute liver failure through the Akt/FoxO3a/Bim pathway. OMT combined with CYG inhibits apoptosis of hepatocytes in rats with acute liver failure via the Akt/FoxO3a/Bim pathway.

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Conflict of interest statement

We declare that there are no conflicts of interest.

Figures

Figure 1
Figure 1
Expression of Akt and p-Akt protein in liver tissues of rats in each group. (a) Protein development diagram of Akt and p-Akt. (b) Statistical graph of transformed data. ##P < 0.01, compared with normal group; ∗P < 0.05,  ∗∗P < 0.01, compared with the model group.
Figure 2
Figure 2
Expression of FoxO3a and p-FoxO3A in liver tissues of rats in each group. (a) Protein development diagram of FoxO3a and p-FoxO3a. (b) Statistical graph of transformed data. #P < 0.05, ##P < 0.01, compared with the normal group; ∗∗P < 0.01, compared with the model group.
Figure 3
Figure 3
Bim protein expression in rat liver tissues of each group. (a) Bim protein development diagram of Bim; (b) statistical graph of transformed data. #P < 0.05, ##P < 0.01, compared with normal group; ∗∗P < 0.01, compared with the model group.
Figure 4
Figure 4
Expression of caspase-3, Bax, and Bcl-2 proteins in liver tissues of rats in each group. (a) Protein development diagram of caspase-3, Bax, and Bcl-2. (b, c) Statistical graph of transformed data. #P < 0.05, ##P < 0.01, compared with normal group; ∗∗P < 0.01, compared with the model group.
Figure 5
Figure 5
Expressions of FoxO3a and Bim mRNA in rat liver tissues of each group. #P < 0.05, ##P < 0.01, compared with normal group; ∗P < 0.05,  ∗∗P < 0.01, compared with the model group.
Figure 6
Figure 6
Expressions of Bax, Bcl-2, and caspase-3 mRNA in liver tissues of rats in each group. #P < 0.05, ##P < 0.01, compared with normal group; ∗∗P < 0.01, compared with the model group.
Figure 7
Figure 7
Apoptosis of rat hepatocytes in each group. (a) Flow cytometry quantitative analysis diagram; (b) statistical graph of transformed data. The lower left quadrant is normal living cells (LL), the upper left quadrant is necrotic cells (UL), the lower right quadrant is early apoptotic cells (LR), and the upper right quadrant is late apoptotic cells (UR). The total apoptotic cells were the sum of UR+LR. ##P < 0.01, compared with normal group; ∗P < 0.05,  ∗∗P < 0.01, compared with the model group.
Figure 8
Figure 8
Expression of active-caspase-3, Bax, and Bcl-2 in liver tissue.
See this image and copyright information in PMC

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