The effect of picroside II on the ERK1/2 signal transduction pathway and its neuroprotective effect on the cerebral ischemic injury in rats

Abstract

Objective To explore the neuroprotective effect and mechanism of picroside II on ERK1/2 signal transduction pathway after cerebral ischemia injury in rats. Methods The focal cerebral ischemic models were established by inserting a monofilament threads into middle cerebral artery occlusion (MCAO) in 100 Wistar rats and treated by injecting picroside II (20 mg/kg) intraperitoneally. The neurobehavioral function was evaluated by modified neurological severity score points (mNSS) test. The cerebral infarct volume was measured by tetrazolium chloride (TTC) staining. The apoptotic cells were counted by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The expression of pERK1/2 in cortex was determined by the immunohistochemistry (IHC) and Western Blot (WB). Results mNSS test showed that severe neurological dysfunction was found in model and LPS groups, and the scores of mNSS were significantly increased; meanwhile the scores of mNSS in treatment group and U0126 group were significantly lower than that in model and LPS groups (P<0.05). TUNEL assay showed that the apoptotic cell indexes (ACI) in different groups were (0.06±0.02), (0.27±0.03), (0.07±0.02), (0.26±0.03)and(0.09±0.05), and the ACI in treatment and U0126 groups was obviously lower than that in model and LPS groups (P<0.05). With IHC and WB, pERK1/2 level in model group was the highest, which was slightly higher than that of LPS group, and pERK1/2 expression in treatment and U0126 groups was significantly decreased compared with that in model and LPS groups (P<0.05). Conclusion The activation of ERK1/2 by cerebral ischemia could induce the cell apoptosis. Picroside II might reduce cell apoptosis by inhibiting the activation of ERK1/2 in ischemic brain injury. Key words: Picroside II; Cerebral ischemia; Apoptosis; ERK1/2; Rats