Abstract
Many traditional Chinese medicines, including Danhong injection (DHI), can be used to treat cerebral ischemia-reperfusion injury and have neuroprotective effects on the brain; however, few studies have explored the mechanism by which this effect is generated. In this study, we investigated the neuroprotective effect of DHI against cerebral ischemia-reperfusion injury mediated via the PI3K-Akt signaling pathway. After establishing the model of middle cerebral artery occlusion (MCAO), 60 male Sprague–Dawley rats were allocated to six groups as follows: sham, MCAO, DHI (MCAO + DHI), LY294002 (MCAO + LY294002 [PI3K-Akt pathway specific inhibitor]), DHI + LY294002 (MCAO + DHI + LY294002), and NMDP + LY294002 (MCAO + NMDP [nimodipine] + LY294002). Hematoxylin and eosin (HE) and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining were used to evaluate the pathological changes of brain tissue and the degree of neuronal apoptosis. Real-time quantitative polymerase chain reaction (qRT-PCR), western blot analysis and enzyme-linked immunosorbent assays were used to measure the expression of Bad, Bax, Bcl-2, Bim, P53, MDM2, Akt, PI3K, p-Akt, p-PI3K, and Cyt-C. Compared with the MCAO group, brain tissue cell apoptosis was significantly reduced in the DHI group, and the brain function score was significantly improved. In addition, the expression of pro-apoptotic factors (Bad, Bax, and Bim) was significantly downregulated in the DHI group, while expression of the anti-apoptotic factor Bcl-2 was significantly upregulated, and expression of the apoptotic gene p53 was also significantly attenuated. Moreover, this neuroprotective effect was attenuated by the PI3K-Akt signaling pathway inhibitor (LY294002). Thus, our results confirmed the neuroprotective effects of DHI in rats with ischemia-reperfusion injury and indicate that these effects on the brain are partly generated by activation of the PI3K-Akt signaling pathway.
Highlights
Of the many types of cerebrovascular diseases, ischemic cerebrovascular disease is the most harmful (Catanese et al, 2017)
Neuronal apoptosis in the Danhong injection (DHI) + LY294002 and NMDP + LY294002 groups was reduced compared to that in the LY294002 group. These findings indicated that DHI has an anti-apoptotic effect after ischemia-reperfusion injury, and this effect is blocked by the PI3K-Akt pathway inhibitor
We confirmed the neuroprotective effect of DHI on brain ischemia-reperfusion damage and provided evidence that this effect is mediated via the PI3K-Akt pathway, since inhibiting the PI3K-Akt signaling pathway weaken the neuroprotective effect of DHI on brain ischemic reperfusion damage in a rat middle cerebral artery occlusion (MCAO) model
Summary
Of the many types of cerebrovascular diseases, ischemic cerebrovascular disease is the most harmful (Catanese et al, 2017). Ischemic cerebrovascular disease is characterized by high morbidity and mortality (Dong et al, 2016); acute ischemic stroke is the main cause of many disabilities related to brain tissue damage in adults (Boers et al, 2013), acute ischemic stroke accounts for 30% of deaths worldwide. Within a few minutes after the onset of ischemic stroke, brain tissue cells begin to undergo necrosis; early thrombolytic therapy can restore blood flow in necrotic areas and reduce mortality in patients with ischemic stroke (Christophe et al, 2017). When the blood flow is restored, oxygen is returned to the ischemic area of the brain to rescue and re-establish neurons (Sanderson et al, 2013). The process of cerebral ischemia is associated with the release of large amounts of oxygen-free radicals combined with calcium overload and inflammatory reactions (Pinton et al, 2008; Raha and Robinson, 2010)
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