Research Article: Sevoflurane Ameliorates Myocardial Cell Injury by Inducing Autophagy via the Deacetylation of LC3 by SIRT1

Date Published: September 26, 2017

Publisher: Hindawi

Author(s): Lihua Fan, Deyuan Chen, Jianping Wang, Yini Wu, Dongli Li, Xiaoyan Yu.


Misfolded and aberrant proteins have been found to be associated with myocardial cell injury. Thus, increased clearance of misfolded or aggregated proteins via autophagy might be a potential option in preventing myocardial cell injury. Sevoflurane may ameliorate myocardial cell injury by affecting sirtuin 1- (SIRT1-) mediated autophagy. Rat models with myocardial cell injury were induced by limb ischemia reperfusion. The model rats received different treatments: sevoflurane, nicotinamide, and autophagy inhibitor 3-methyladenine (3-MA). Autophagy was observed by SEM. The levels of SIRT1 and microtubule-associated protein 1A/1B-light chain 3 (LC3) were measured. Present findings demonstrated that limb ischemia reperfusion induced autophagy. Sevoflurane increased the level of SIRT1, which deacetylated LC3 and further increased autophagic rates. On the other hand, the autophagy was inhibited by sevoflurane and or the inhibitors of SIRT1 and LC3. Present results demonstrated a novel molecular mechanism by which sevoflurane induced autophagy by increasing the level of SIRT1 and reducing the acetylation of LC3.

Partial Text

Limb ischemia is a severe obstruction of the arteries, and surgery is often considered, including vascular surgery, abdominal aortic aneurysm surgery, limb replantation, and arterial embolization. Although restoring blood circulation is necessary to save ischemic limbs, a large number of clinical and animal experiments show that severe limb ischemia and reperfusion not only affect the survival and functions of ischemic tissue but can also cause systemic inflammatory response syndrome (SIRS) [1]. SIRS affects the heart, liver, lung, kidney, and other vital organs [2], and all these may lead to multiple organ dysfunction syndrome (mODS) [3].

The method, femoral artery was ligated and then opened, provides a simple way for establishing a rat model with ischemic reperfusion tissues. Chen et al. use noninvasive arterial occlusion and then reperfuse to setup an animal ischemia reperfusion model [16]. Meanwhile, the apoptosis factor BAX was found to be upregulated in the model when compared with a control. The present study also used this method to establish a rat model with hind limb ischemia reperfusion. After femoral artery occlusion, rat paws became cold and turned purple, suggesting that the limb ischemia model was successfully established. The bilateral femoral arteries were occluded and reperfused, and myocardial cells showed granular degeneration, vacuolar degeneration, osteoporosis, transparent cytoplasm, break muscle fibers, more myocardial interstitial neutrophils, and red blood cell infiltration (Figure 2). Apoptosis was detected in all models and reduced by sevoflurane, SIRT1, and autophagy inhibitors. Apoptosis is an important character of the ischemia reperfusion model [17]. All the results suggested that limb ischemia reperfusion was successfully established.

Limb ischemia and reperfusion increase SIRT1 and LC3 expression in rat myocardial tissues. Sevoflurane mitigates the limb ischemia reperfusion-induced injury by inducing myocardial autophagy via the increase in the concentrations of SIRT1 and deacetylated LC3.




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