北五味子乙素对大鼠心脏成纤维细胞增殖的抑制作用及其PI3K/Akt/P27kip1信号通路机制

doi:10.13481/j.1671-587X.20220107

Abstract

Abstract: Objective

To observe the effects of Schisandrin B（SchB）， one of the monomers of lignans from Schisandra chinensis， on the proliferation， cell cycle， type Ⅰ collagen and type Ⅲ collagen expression levels in the neonatal SD rat cardiac fibroblasts（CFb） induced by angiotensinⅡ（AngⅡ）， and to explore the mechanisms of phosphatidylinositol 3-kinase/protein kinase B/cell cycle inhibiting protein（P27kip1）（PI3K/Akt/P27kip1）signal pathways.

Methods

The myocadium tissue was obtained from the neonatal 1－3 d of SD rats.The CFb were cultured by trypsin digestion and differential adhesion method and identified as the required CFb.The experiment was divided into control group， model group， LY294002（PI3K inhibitor） group，SchB group，LY294002+SchB group.The CFb were stimulated with 0.1 μmol·L^－1 AngⅡ，and the inhibitory rates of proliferation of CFb were detected by MTT colorimetry after treated for 24 h.The expression levels of typeⅠand type Ⅲ collagen proteins were detected by immunohistochemistry method，the percentages of CFb in different cell cycle in various groups were detected by flow cytometry.The expression levels of PI3K， Akt， phosphorylated Akt（p-Akt） and P27kip1 proteins in the CFb in various groups were detected by Western blotting method.

Results

Compared with control group， the inhibitory rate of proliferation of the CFb in model group was increased（P<0.01）， the exspression levels of typeⅠ collagen and type Ⅲ cellagen proteins were increased（P<0.01），the percentage of CFb in G₀/G₁ phase was decreased（P<0.01）， the percentage of CFb in S phase and the proliferation index（PI） were increased（P<0.01），the expression levels of PI3K and Akt proteins in the CFb were increased（P<0.01）， and the expression level of P27kip1 protein was decreased（P<0.01）；compared with model group， the inhibitory rates of prolifenition of the CFb in LY294002， SchB，and LY294002+SchB groups were significantly decreased（P<0.05 or P<0.01）， the expression levels of typeⅠand type Ⅲ collagen proteins were significantly decreased（P<0.05 or P<0.01）， the percentages of CFb in G₀/G₁ phase were increased（P<0.05 or P<0.01）， the percentages of CFb in S phase and PI were decreased（P<0.05 or P<0.01）， the expression levels of PI3K and p-Akt proteins were decreased（P<0.05 or P<0.01）， and the expression levels of p27kip1 proteins were increased（P<0.05 or P<0.01）.

Conclusion

SchB can inhibit the AngⅡ-induced CFb proliferation and collagen deposition， and its mechanism may be related to inhibiting the PI3K/Akt/P27kip1 signal transduction pathways.

Key words: Schisandrin B, Phosphatidylinositol 3-kinase, Protein kinase B, Cardiac fibroblast, Signal pathway

CLC Number:

R285.5

Chunxu LIU,Hongxia SUN,Bo HU,Enping JIANG. Inhibitory effects of Schisandrin B on cardiac fibroblast proliferation and its PI3K/Akt/P27kip1 signaling pathway mechanism[J].Journal of Jilin University(Medicine Edition), 2022, 48(1): 52-58.

Figures/Tables 5

Tab. 2

Tab. 3

Fig. 1

Fig. 2

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Group		Inhibitory rate of proliferation（η/%）
Control		0
Model		53.56±7.32^*
LY294002		33.70±5.28^△
SchB		29.74±4.77^△
LY294002+SchB		48.27±5.39^△△

Group	Percentage of CFb			PI
Group	G₀/G₁	S	G₂/M	PI
Control	83.2±3.6	10.4±3.2	6.5±1.6	16.8±3.8
Model	73.6±7.4^*	20.7±6.5^*	5.7±1.9	26.4±4.2^*
LY294002	78.4±3.2^△	15.8±2.5^△	5.8±2.3	21.6±4.3^△
SchB	85.1±2.6^△△	12.3±2.6^△	2.6±2.3	14.9±4.2^△
LY294002+SchB	92.7±4.7^△△#	5.3±1.8^△△＃	2.0±3.2	7.3±3.1^△△#

Group	TypeⅠcollagen	Type Ⅲ collagen
Control	0.66±0.13	0.59±0.08
Model	1.57±0.15^*	1.29±0.14^*
LY294002	0.83±0.19^△	0.53±0.17^△
SchB	0.68±0.07^△△	0.47±0.04^△△
LY294002+SchB	0.47±0.06^△△＃	0.37±0.05^△△＃

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Inhibitory effects of Schisandrin B on cardiac fibroblast proliferation and its PI3K/Akt/P27kip1 signaling pathway mechanism

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