2013年11月15日星期五

The effects of Astragaloside IV

Ischemic heart disease is among the top causes of death in the world . PCI has currently been applied widely to deal with acute coronary syndrome, myocardial infarction and stable angina. Although PCI can restore  the blood flow in  myocardium rapidly, it does  not  reduce the risk of serious heart events because of reperfusion injury . Thus, strategy  to prevent reperfusion injury and improve PCI outcome is currently appealing in clinic.   

Here are some part of conclusions about Astragaloside IV ,it may give some suggestions to protect heart from ischemia and reperfusion injury via energy regulation mechanism.

Effect of Astragaloside IV on myocardial infarct size 

The effect of Astragaloside IV(CAS NO:84687-43-4) on myocardial infarct size at different doses was determined by Evans blue-TTC staining. As showing in the Figure 2A, the pink area represents ischemic myocardial tissue, the white area represents the infarction region, and the blue area represents normal myocardial tissue. We found that Astragaloside IV was effective  at the dose of 10 mg/kg,  and thus chose this dose for all the experiments below. The representative heart slices in I-30 min and I/R-90 min groups are shown in Figure 3A and Figure 3D, respectively. Obviously, myocardial tissue slices from I-30 min group exhibited ischemia but no infarct. 

By contrast, noticeable ischemia and infarct areas were observed in myocardial tissue slices in I/R-90 min group. As compared to I/R-90 min group, pretreatment with Astragaloside IV significantly decreased the I/R-90 min induced myocardial infarct size, but retained a similar area of ischemic region. As shown in Fig.3.B-C, E-F, quantitative analysis of AAR/ LV and infarct area/AAR confirmed the above results.   

Effect of Astragaloside IV on MBF 

Figure 4A shows the color images acquired by the Laser Scanning Doppler in the four groups at different time point. A prominent decrease in MBF occurred from 30 min after ischemia, and persisted till 90 min after reperfusion in I/R-group. Astragaloside IV pretreatment prevented MBF from decrease at 30 min ischemia, and this protective role remained by I/R-90 min. Figure 4B is the quantitative evaluation of MBF changes in the four groups, which confirmed the impression from Figure 4A.  

Effect of Astragaloside IV on heart function 

Heart function was assessed in different conditions to evaluate the role of Astragaloside IV in protecting heart against ischemia and reperfusion injury. As noticed in Fig.5, in comparison with Sham group, ischemia 30 min caused a significant decline in +dp/dtmax, and an apparent elevation in LVDP, LVEDP and -dp/dtmax, indicating an impairment on heart function. Reperfusion for 90 min led to a further decline in +dp/dtmax as well as a significant decrease in LVSP, and a sustained increase in -dp/dtmax, but did not deteriorate LVDP and LVEDP. The protective role of Astragaloside IV pretreatment for LVDP and LVEDP exhibited already at 30 min ischemia, but only at 90 min reperfusion for other parameters examined. No significant change was observed in heart rate in any group over the observation, nor among the groups at any time point (Fig.5A).  

In conclusion, Astragaloside IV pretreatment protected against myocardium injury and cardiac malfunction after I/R, which may be related to its potential to restore the  energy  metabolism disorder occurred in ischemia phase. The results provide support for Astragaloside IV as a novel therapeutic approach to protect against I/R-induc ed myocardial injury. In addition, the results of present study opened an avenue for development of new drug to cope with cardiac I/R injury by targeting energy metabolism.

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