| Aim:To investigate whether astragaloside IV (AS-IV), remote ischemic post conditioning(RIPOST) and combined therapy could improve cardiac function with rats received LAD ligation.Methods:60 rats received LAD ligation were randomly seperated into 4 groups:model group (n=15)、AS-IV group (n=15)、RIPOST group (n=15)、combined group (AS-IV+RIPOST) (n=15); another 10 rats served as sham group. AS-IV were intragastric administrated for 2weeks (50mg/kg/d); rats in RIPOST group received 3 cycles of 5 min left limb ligation followed by 5min reperfusion with tourniquet at groin in one day for 2weeks; combined group receive both AS-IV and RIPOST for 2 weeks; equal normal saline were intragastric administrated every day in model group, sham group and RIPOST group. After intervening for 2 weeks, drew survival curves of rats, cardiac function were detected by echocardiography, hearts were harvested and weighed, infarcted size were measured by TTC staining, H-E staining and Masson staining were employed to observe lesion tissue, we also adapted immunohistochemistry to detect apoptosis, Western Blot was utilized to detect p-AKT, VEGF, Bcl-2, Bax, NF-κB and iNOS expression.Results:1.AS-IV, RIPOST and combined therapy were equally able to improve survival rate of AMI rats, combined therapy led to more statistically significant improve of survival rate (P=0.0114), but there was no statistical difference in combined group versus AS-IV group (P=0.1903) and combined group versus RIPOST group (P=0.0835)2. AS-IV, RIPOST and combined therapy were equally capable of enhancing AMI rats’cardiac function, improving LVEF and LVFS, compared with AI-IV group and RIPOST group* combined group had a better therapeutic effect. (P<0.01)3.Compared with model group, heart weight/body weight ratio (HW/BW) in AS-IV, RIPOST and combined group were reduced in different extent (P<0.01,repectively); combined therapy led to the most significant reduction, AS-IV group took second place, RIPOST group was the last. There was statistical significance between combined group and RIPOST group. (P<0.05)4.AS-IV, RIPOST and combined therapy had an effect on reducing infarct size (P<0.01), combined group had a better effect than AS-IV group and RIPOST group. (P<0.01)5. Pathological changes and fibrosis were attenuated in all three treated group, compared with AS-IV and RIPOST group, combined therapy achieved the optimize protection.6. α-SMA immunohistochemical proved that arteriole around infarct site were promoted in all three treated group, combined therapy was more efficient than AS-IV or RIPOST alone(P<0.01); compared with model group, AS-IV and RIPOST were both able to upregulate VEGF and p-AKT (P<0.01), meanwhile, combined group had a synergistic effect.7. Compared with model group, expression of NF-κ B/iNOS in AS-IV, RIPOST and combined group were downregulated in different extent, combined group had the best anti-inflammation effect. (P<0.01,repectively) All three groups had the potential of anti-apoptosis by upregulating anti-apoptosis factor(Bcl-2) and downregulating pro-apoptosis factor(Bax) (P<0.01,repectively), combined group had a synergistic effect. Tunel/DAPI immunofluorescence of myocardial tissue confirmed these conclusions in histopathological way.8. Compared with model group, the extent of ultrastructural pathology injury was ameliorated in AS-IV and RIPOST group, RIPOST group had a better recovery; however, combined group suffered the slightest injury.Conclusion:Our results demonstrate that AS-IV and RIPOST were equally able to improve cardiac function after myocardial infarction, minimize infarcted size, surpress inflammation, inhibit apoptosis, reduce fibrosis and promote angiogenesis, ameliorate ultrastructural pathology injury, and combination of the two treatment strategy had the most potent effect, which indicates that AS-IV could enhance RIPOST’s cardioprotection. |
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