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. 2018 Dec;16(6):5161-5165.
doi: 10.3892/etm.2018.6822. Epub 2018 Oct 2.

The role of PI3-K/Akt signal pathway in the antagonist effect of CEPO on CHF rats

Zhaoqi Huang  1 , Wei Xu  2 , Jinlei Wu  3 , Shengqiang Chen  4 , Ximing Chen  1
Affiliations

The role of PI3-K/Akt signal pathway in the antagonist effect of CEPO on CHF rats

Zhaoqi Huang et al. Exp Ther Med. 2018 Dec.

Abstract

The possible role of phosphoinositide 3-kinase (PI3-K)/protein kinase B (Akt) signal pathway in the antagonist effect of carbamylated erythropoietin (CEPO) on chronic heart failure (CHF) in rats was investigated. Twenty of 120 rats were randomly selected as the control group, and the remaining rats as the model group. Rats in the model group received intraperitoneal injection of isoproterenol, those in the control group underwent intraperitoneal injection of equivalent normal saline. Rats with successful model establishment were divided into 4 groups, i.e. CHF group, CEPO group, LY294002 (LY) group and CEPO + LY group. Rats in the CEPO group underwent intraperitoneal injection of CEPO, while those in the CHF group received intraperitoneal injection of equivalent normal saline at the same time, those in the LY group received intraperitoneal injection of LY after model establishment, and those in the CEPO + LY group received the combined intraperitoneal injection of CEPO and LY simultaneously. Indicators for hemodynamics were determined using BL-410S bio-functional experiment system, including heart rate (HR), left ventricular end-diastolic pressure (LVEDP), left ventricular systolic pressure (LVSP) and maximal increased rate of left ventricular pressure (LVP)/maximal reduced rate of LVP (±dp/dtmax). Western blotting assay was utilized to determine the changes in activity of PI3-K/Akt signal pathway. LVSP and ±dp/dtmax in the CHF, the CEPO, the CEPO + LY and the LY groups were significantly lower than those in the control group (P<0.05); LVSP and ±dp/dtmax in the CEPO group were also elevated significantly compared with CHF, LY and CEPO + LY groups (P<0.05) with significant decreases in LVEDP and HR (P<0.05); compared with the CHF group, LVSP and ±dp/dtmax in the LY group were each significantly decreased (P<0.05), in the LY group, pAkt level was significantly lower than that in the CHF group (P<0.05). In conclusion, CEPO can generate the antagonist effect on CHF in rats through activation of PI3-K/Akt signal pathway.

Keywords: CEPO; CHF; PI3-K/Akt; hemodynamics.

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Figures

Figure 1.
Figure 1.
Expression of Akt and pAkt in rats of all groups. Expression of Akt and pAkt in rats of all groups through western blotting assay. Akt, protein kinase B; pAkt, phosphorylated Akt; CHF, chronic heart failure; CEPO, carbamylated erythropoietin; LY, LY294002.
Figure 2.
Figure 2.
Statistical diagram of relative expression of pAkt. #P<0.05 in comparison with the CEPO group; △P<0.05 in comparison with the LY group; *P<0.05 in comparison with the CHF group; ▲P<0.05 in comparison with the control group. Akt, protein kinase B; pAkt, phosphorylated Akt; CHF, chronic heart failure; CEPO, carbamylated erythropoietin; LY, LY294002.
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