In Vivo Study on Doxycycline Protective Mechanisms during Myocardial Ischemia Injury in Rats

强力霉素对大鼠心肌缺血损伤保护机制的体内研究

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作者:Anna Krzywonos-Zawadzka, Agnieszka Olejnik, Grzegorz Sawicki, Iwona Bil-Lula

Background

The fact that during myocardial ischemia/reperfusion (I/R) injury, myosin light chain 1 (MLC1) and troponin I (TnI) are degraded by matrix metalloproteases activity has already been well established in both in vitro and ex vivo studies. However, I/R injury is a complex issue based on several overlapping mechanisms. Increased activity of myosin light chain kinase and nitric oxide synthase due to oxidative stress leads to post-translational modifications of MLC1, thus leading to the increased degradation of these proteins.

Conclusions

Inhibition of MMPs by doxycycline, in vivo, may serve as a protective agent in future therapy.

Methods

Wistar rats were subjected to left anterior descending coronary artery occlusion. To measure the pharmacological effect of doxycycline, transthoracic echocardiography as well as biochemical tests, concentrations of TnI, LDH, MLC1, MMP-2 and MMP-9 were performed. Gelatinize activity and cytotoxicity level were also assessed;

Results

I.p., administration of doxycycline before LAD occlusion surgery increased TnI and LDH content in the heart and decreased cytotoxicity. A reduction of MMP-2 and MMP-9 concentration and MMP-2 activity after administration of Doxy was also observed, as well as improvement in echocardiographic parameters just 7 days after surgery. Conclusions: Inhibition of MMPs by doxycycline, in vivo, may serve as a protective agent in future therapy.

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