Protective effect and mechanism of quercetin on learning and memory function after global ischemia/reperfusion injury in rats

Abstract

Objective To observe the effect of quercetin (Que) on neurological behavior, cell apoptosis and apoptosis-related protein expression in hippocampus after global cerebral ischemia/reperfusion (I/R) injury. Exploring the mechanism of quercetin-induced neuroprotective effect against global cerebral I/R injury. Methods Seventy two Male SD rats were randomly divided into 4 groups (n=18): sham+vehicle group (S group), I/R+vehicle group (I/R group), I/R+Que 5 mg·kg-1·d-1 group (Q5 group) and I/R+Que 10 mg·kg-1·d-1 group (Q10 group). The global cerebral ischemia reperfusion model was established by a four-vessel occlusion (4-VO) ligation method, and the duration of ischemia was 15 min. Sham-operated animals were treated similarly to those in the ischemic group, but neither the vertebral arteries nor the common carotid arteries were occluded. The rats in Q5 group and Q10 group were administered with 0.05%, 0.10% of the quercetin solution by garage at the dose of 5 mg·kg-1·d-1 and 10 mg·kg-1·d-1 respectively. S group and I/R group were given equal volume of vehicle. The quercetin and vehicle were administrated by gavage once per day 3 d before I/R and continued till the end of observation. The Morris maze test was performed 8 d after reperfusion. At 24 h after reperfusion, TUNEL staining and Annexin V-FITC/PI double labeled flow cytometry were used to evaluate apoptosis in hippocampus tissue, the expressions of Bcl-2, Bcl-xl, survivin, cleaved caspase-3, phosphorylated protein kinase B(p-Akt), Bad, p-Bad protein were determined by Western blot. Results In Morris water maze test, escape latency results showed that compared with I/R group, the escape latency in Q5 group and Q10 group was obviously reduced (P<0.05). Space probe test showed that the active time in the target quadrant in Q5 group and Q10 group were significantly longer than active time in the target quadrant (P<0.05). The frequency of crossing the original position platform was significantly increased (P<0.05). TUNEL assay showed that a large number of apoptotic cells in I/R group, while less positive cells could be seen in Q5 group and Q10 group. Annexin V-FITC/PI double staining flow cytometry detection results showed that the proportion of apoptotic cells in Q5 group and Q10 group were significantly reduced (P<0.05). Western blot results showed that Bcl-2, Bcl-xl, survivin, p-Akt and p-Bad expression levels were significantly increased in Q5 group and Q10 group (P<0.05) while cleaved caspase-3 expression level was significantly decreased (P<0.05). Conclusions Quercetin can up-regulate the expression of p-Akt, p-Bad, Bcl-2, Bcl-xl and survivin while down-regulate the expression of cleaved caspase-3, which leads to the inhibition of apoptosis, eventually protects neuron cells from global cerebral I/R injury and improves the learning and memory function. Key words: Quercetin; Cerebral ischemia-reperfusion; Learning; Memory; Hippocampus; Apoptosis