Abstract
Objectives To evaluate the protective effect of Buyang Huanwu Decoction (BHD) against cerebral ischemia reperfusion and investigate whether autophagy is involved in its mechanism of action. Methods Adult male Sprague Dawley rats were randomly divided into three groups: the sham, cerebral ischemia reperfusion (I/R), and I/R + BHD groups. A rat model of cerebral I/R injury was established via middle cerebral artery occlusion (MCAO) for 2 h, followed by 1, 3, and 7 d of reperfusion. Neurological scores and regional cerebral blood flow were assessed to determine whether the model was successfully established. Brain infarct volume was determined by 2,3,5-triphenyl tetrazolium chloride (TTC) staining. The apoptosis rate was detected using TdT-mediated dUTP Nick-End Labeling (TUNEL) staining, and neuronal damage was evaluated by Nissl staining. The Beclin-1 and LC3 protein levels in the ischemic core, penumbra, and contralateral area were analysed by Western blotting. The occurrence of autophagy in the penumbra was observed by transmission electron microscopy (TEM). Results BHD treatment alleviated the cerebral infarct volume, neuronal apoptosis rate, and neuronal damage 3 and 7 d after cerebral I/R injury. Furthermore, 3 d after reperfusion, we observed that the Beclin-1 levels were significantly decreased in the core in the I/R group, whereas transformation of LC3 I to LC3 II exhibited no obvious differences between the sham and I/R groups. In the penumbra, the Beclin-1 levels and transformation of LC3 I to LC3 II in the I/R group were significantly increased compared with that in the sham group. However, no significant difference in the contralateral area was noted between the two groups. BHD significantly inhibited the expression of Beclin-1 and the transformation of LC3 I to LC3 II in the penumbra after cerebral I/R injury but yielded no significant changes in the core and contralateral area. Conclusions BHD exerts a neuroprotective effect by inhibiting autophagy in neurons in the penumbra after cerebral I/R injury.
Highlights
Stroke is one of the leading causes of death and disability worldwide, and 60–80% of stroke cases are ischemic stroke [1, 2]
The neurofunctional score of rats with middle cerebral artery occlusion (MCAO)/R was 2.29 ± 0.66, and the rats were randomly divided into an ischemia reperfusion (I/R) group and an I/R + Buyang Huanwu Decoction (BHD) group
We evaluated the neuroprotective effects of BHD at 1, 3, and 7 d after reperfusion. e data demonstrated that BHD can significantly reduce cerebral infarct volume, apoptosis rate, and neuron damage at 3 d and 7 d after reperfusion
Summary
Stroke is one of the leading causes of death and disability worldwide, and 60–80% of stroke cases are ischemic stroke [1, 2]. Accumulating evidence shows that autophagy is activated in cerebral I/R injury, and regulation of the autophagy process may represent a potential therapeutic strategy in the treatment of cerebral I/R injury [5,6,7]. Autophagy normally functions to promote cell survival, but excessive autophagy can lead to cell death called “autophagic cellular death” [7]. E proper execution of autophagic programmes requires Atg proteins [7]. As Atg proteins, Beclin-1 and LC3 play an important role in the autophagy regulation process and are key indicators for detecting autophagy levels. LC3 II is tightly correlated with the number of autophagosomes and is considered the Evidence-Based Complementary and Alternative Medicine most reliable marker of active autophagosomes and autolysosomes [8]
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