| Objective: To investigate the effect and mechanism of Astragaloside IV(ASIV)on cardiac hypertrophy induced by abdominal aorta constriction in rats.Methods: 24 spf-grade sprague-dawley(SD)healthy male rats,aged4-6 weeks and about 280g-300 g,were selected for adaptive feeding for 3days,and 6 rats were randomly selected as the sham group.In addition,the balloon injury method was used to establish the balloon damage vessel model of the common carotid artery in rats.The experiment was divided into four groups: sham operation group,model group,low-dose ASIV group and high-dose ASIV group.The low-dose ASIV group was given ASIV at 60mg·kg-1·d-1,the high-dose ASIV group was given ASIV at 120mg·kg-1·d-1,and the sham operation group and model group were given 1% sodium carboxymethyl cellulose by gavage.After 4 weeks,the common carotid artery of the injured rats was taken for paraffin sectioning,and the lumen morphology was observed under light microscope.The lumen area,intimal hyperplasia degree and intimal medium membrane ratio were evaluated by image analysis software.The proliferation index(Ki67),differentiated cluster 3(CD3)and differentiated cluster 68(CD68)were determined by immunohistochemistry.Phosphorylated phosphatidylinositol 3-kinase(p-pi3k),phosphatidylinositol 3-kinase(PI3K),phosphorylated protein dinase B(p-akt),protein dinase B(protein dinase B,Akt),phospholator-mammlian target of rapamycin(p-mtor),mammlian target of rapamycin(mTOR),proliferating cell nuclear antigen(PCNA),?-smooth muscle actin(?-sma),intercellular cell adhesion molecule-1(ICAM-1),microtube-associated protein 1 light chain 3B(LC3B),and P62.To determine the inhibitory effect of ASIV at different doses on intimal hyperplasia in rats with balloon injury of the common carotid artery and the expression of phosphorylated proteins and total proteins in the PI3K/Akt/mTOR signaling pathway.Results:1.Compared with the sham operation group,the degree of intimal hyperplasia in the model group was significantly increased(P<0.05),and the area of the vascular cavity was reduced compared to the previous(P<0.05).There was no statistical difference in the change of the media(P>0.05).Compared with the model group,intimal hyperplasia was inhibited in the ASIV group(P<0.05),and the vascular lumen area increased(P<0.05)in a dose-dependent manner,with no significant change in the median area(P> 0.05).2.Compared with the sham operation group,the expressions of CD3 and CD68 in the model group were significantly increased(P<0.05),and the expressions of CD3 and CD68 were reduced after ASIV treatment(P<0.05)and were dose-dependent.3.Compared with the sham operation group,the serum levels of IL-6,TGF-?1,TGF-?2,TNF-?,IL-1? and other inflammatory cytokines in the model group were significantly up-regulated,and related inflammatory cytokines were expressed after ASIV intervention.suppressed.4.Compared with the sham operation group,PCNA,Ki67,Clo-1,?-catenin and other factors were significantly increased in the model group(P<0.05);compared with the model group,the expression of related factors was inhibited after ASIV intervention(P<0.05),and was dose-dependent.5.Compared with the sham operation group,the expression of PCNA and ICAM-1 protein in the common carotid artery tissue of the model group increased,while the expression of ?-SMA protein decreased(P<0.05).Compared with the model group,the PCNA,The expression of ICAM-1 protein decreased and the expression of ?-SMA protein increased(P <0.05).6.Compared with the sham operation group,the expressions of P-PI3 K / T-PI3 KT,P-Akt / T-Akt,P-mTOR / T-mTOR protein in the common carotid artery tissue of the model group rats were reduced(P<0.05),Compared with the model group,P-PI3 K / T-PI3 KT,P-Akt /T-Akt,and P-mTOR / T-mTOR protein expression protein levels wereincreased(P <0.05).7.Compared with the sham operation group,the expression of P62 protein in the common carotid arteries of the model group was reduced(P<0.05),compared with the model group,the level of P62 in the ASIV group was increased(P<0.05);compared with the sham operation group,Compared with the model group,LC3 B protein expression was increased(P<0.05),compared with the model group,LC3 B expression was decreased(P<0.05).Conclusion:1.ASIV can inhibit intimal hyperplasia after balloon injury of common carotid artery in rats,mainly by inhibiting proliferation,migration and phenotypic transformation of vascular smooth muscle cells.2.ASIV can play an anti-restenosis role by activating PI3K/Akt/mTOR signaling pathway to inhibit autophagy. |
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