| Objective:To investigate the mechanism of PTEN/Akt signaling pathway in the effect of salvianolic acid A on isoproterenol-induced myocardial remodeling injury in mice by observing the effect of salvianolic acid A on isoproterenol-induced myocardial remodeling injury.Methods: In this experiment,several age-appropriate SPF-grade Kunming mice were randomly selected and myocardial remodeling was induced by intraperitoneal injection of isoprenaline to construct a myocardial remodeling injury model.1.The mice were divided into control group,model group,low-dose administration group,and high-dose administration group,and 8 mice in each group were injected intraperitoneally with the corresponding drugs(control group took equal volume of(control group took equal volume of saline).The mice were visually observed for heart size and weighed for heart weight and body weight to assess the heart-to-weight ratio;HE staining was used to observe the histopathological sections and assess the pathological damage;WB was used to detect the expression levels of cardiac hypertrophy-related proteins.2.The mice were divided into control group,positive control group,model group,and drug administration group,and 10 mice in each group were injected with the corresponding drugs intraperitoneally(equal volume of saline was taken for the control group).The heart size was observed visually and the heart weight and body weight were weighed to assess the heart-to-weight ratio;HE and Masson staining were used to observe the histopathological sections and assess the pathological damage;the levels of lipid peroxides malondialdehyde(MDA)and glutathione(GSH)in the serum were measured using relevant kits to assess the level of oxidative stress in the heart;the expression of PTEN in the heart tissue was detected by immunofluorescence.The expression of PTEN in cardiac tissues was measured by immunofluorescence;the expression levels of myocardial hypertrophy,oxidative stress,inflammation,fibrosis and PTEN signaling pathway-related proteins in mice were detected and analyzed by WB.3.Mice were divided into control group,positive control group,model group,drug administration group,and inhibitor group,and 10 mice in each group were injected intraperitoneally with the corresponding drugs(equal volume of saline was taken for the control group).The heart size was observed visually and the heart weight and body weight were weighed to assess the heart-to-weight ratio;HE staining and Masson staining were used to observe the pathological sections of mice heart tissues and assess the pathological damage;serum levels of lipid peroxides malondialdehyde(MDA)and glutathione(GSH)were measured by relevant kits;WB was used to detect and analyze myocardial hypertrophy,oxidative stress,inflammation,fibrosis and PTEN signaling pathway-related damage in mice,The expression levels of proteins related to myocardial hypertrophy,oxidative stress,inflammation,fibrosis and PTEN signaling pathway were measured by WB.Results:1.The results of heart-to-weight ratio showed that the model group was significantly larger than the control group,while the heart-to-weight ratios of low-dose administration group and high-dose administration groups were smaller than the model group,and the heart-to-weight ratio of low-dose administration group was smaller than that of high-dose administration group;HE staining results showed that the inflammatory damage in the model group was more serious than that in the control group,and the inflammatory damage was reduced after drug administration,and the effect of reducing inflammatory damage in the low-dose administration group was better than that in the high-dose administration group.The WB results showed that compared with the control group,BNP and β-MHC protein expression was upregulated in the model group(P<0.05),and protein expression was downregulated in both the low-dose administration and high-dose administration groups(P<0.05),and the downregulation of protein expression was more significant in the low-dose administration group than in the high-dose administration group(P<0.05).2.The results of heart weight ratio showed that the model group was significantly larger than the control group,and the heart weight ratio of drug administration group was smaller than the model group;HE staining results showed that the inflammatory damage was more severe in the model group compared with the control group,and significantly reduced in the drug administration group compared with the model group;Masson staining results showed that the myocardial fibrotic damage was significantly increased in the model group compared with the control group,and significantly reduced in the drug administration group compared with the model group;serum test results showed that the GSH expression level was significantly reduced in the model group compared with the control group,and the MDA expression level was significantly increased compared with the model group.Masson staining showed that myocardial fibrotic injury was significantly increased in the model group compared to the control group,and reduced in the drug administration group compared to the model group;serum assays showed that GSH expression levels were significantly decreased and MDA expression levels were significantly increased in the model group compared to the control group,and GSH expression levels were upregulated and MDA expression levels were downregulated in the drug administration group compared to the model group;immunofluorescence results showed that compared to the control group The immunofluorescence results showed a significant decrease in PTEN positive expression in the model group compared to the control group,and an increase in PTEN positive expression in the drug administration group compared to the model group;WB results showed that the expression of BNP,β-MHC,TNF-α,IL-6,Collagen I,p-Akt1,TGF-β,p-Smad2 and p-NF-κB proteins were significantly increased in the model group compared to the control group were significantly increased(P<0.05),SOD,CAT and PTEN protein expressions were significantly decreased(P<0.05),and BNP,β-MHC,TNF-α,IL-6,Collagen I,p-Akt1,TGF-β,p-Smad2 and p-NF-κB protein expressions were significantly decreased in the drug administration group compared with the model group(P<0.05),and SOD,CAT and PTEN protein expressions were significantly increased(P<0.05)3.The results of the heart-to-weight ratio showed a significant increase in the model group compared to the control group,a smaller heart-to-weight ratio in the drug administration group compared to the model group,and an increase in the heart-toweight ratio in the inhibitor group compared to the drug administration group;HE staining results showed a significant increase in inflammatory injury in the model group compared to the control group,and a decrease in inflammatory injury in the drug administration group compared to the model group.Masson staining showed that compared to the control group,myocardial fibrosis injury was significantly aggravated in the model group,while it was significantly reduced in the drug administration group compared to the model group,and aggravated in the inhibitor group compared to the drug administration group;WB results showed that compared to the control group,myocardial fibrosis injury was significantly aggravated in the model group,while it was significantly reduced in the drug administration group compared to the model group.Compared with the model group,the expression of BNP,β-MHC,TNF-α,IL-6,Collagen I,p-Akt1,TGF-β,p-Smad2 and p-NF-κB proteins were significantly increased(P<0.05)and the expression of SOD,CAT and PTEN proteins were significantly decreased(P < 0.05)in the drug administration group compared with the model group BNP,β-MHC,TNF-α,IL-6,Collagen I,p-Akt1,TGF-β,p-Smad2 and pNF-κB protein expressions were significantly decreased(P<0.05)and SOD,CAT and PTEN protein expressions were significantly increased(P<0.05)in the inhibitor group compared to the drug administration group,BNP,β-MHC,TNF-α,IL-6,Collagen I,pAkt1,TGF-β,p-Smad2 and p-NF-κB protein expressions were increased to different degrees,and SOD,CAT and PTEN protein expressions were decreased to different degrees(P<0.05).Conclusion: Studies have shown that salvianolic acid A ameliorates the inflammation,fibrosis and oxidative stress associated with myocardial remodeling induced by isoproterenol,and its protective effects may be related to the inhibition of PTEN degradation and activation of Akt downstream signaling pathways and thereby inhibiting oxidative stress,inflammation and fibrotic effects. |
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