Abstract: Objective: To explore the effect of ginsenoside Rg1 on the ubiquitin-modified protein aggregation in the cortex after cerebral ischemia reperfusion(I/R) injury in the rats, and to further clarify the therapeutic mechanism of ginsenoside Rg1 in the cerebral I/R injury.Methods: The middle cerebral artery occlusion (MCAO) model was set up with suture method for 1.5 h of embolization. A total of 72 rats were divided into sham operation group, I/R model group,positive drug control (nimodipine) group, low, middle,and high doses(10, 20, and 40 mg·kg^-1) of ginsenoside Rg1 groups. All 12 rats in each group were given intraperitoneal injection. TTC staining and Longa's score method were used to detect the infarction areas and the neurological deficit scores of the rats in various groups 24 h after modeling. The death of neurons in the cortex and hippocampus after cerebral ischemia of the rats in various groups were observed with HE staining.Immunohistochemistry and Western blotting method were used to detect the expression of ubiquitin-modified protein aggregation in the cortex of the rats in various groups.Results: Compared with I/R group, the percentages of infarction areas of the rats in nimodipine group and ginsenoside Rg1 groups were significantly decreased(P<0.05). and the neurological deficit scores were decreased(P<0.05).The HE staining results showed that compared with sham operation group, the neurons in I/R model group were sparse, showing fragmentation and dissolution;compared with I/R model group, the phenomena of cell nucleus fragmentation, dissolution and powder staining in nimodipine group and different doses of ginsenoside Rg1 groups were all improved to different degrees. The immunohistochemical results showed that compared with sham operation group, the positive expression level of ubiquitin-modified protein in I/R model group was increased significantly(P<0.05); compared with I/R model group,the positive expression levels of ubiquitin-modified protein in nimodipine group and different doses of ginsenoside Rg1 groups were decreased (P<0.05),especially in high dose of ginsenoside Rg1 group (P<0.05). The Western blotting results showed that compared with sham operation group, the level of ubiquitin-modified protein aggregates in I/R model group was significantly increased(P<0.05);compared with I/R model group, the levels of ubiquitin-modified protein aggregates in nimodipine group and different doses of ginsenoside Rg1 were decreased(P<0.05), especially in high dose of ginsenoside Rg1 group.Conclusion: Ginsenoside Rg1 can inhibit the formation of ubiquitin-modified protein aggregates induced by I/R injury in the cortex, thereby alleviating the I/R injury in the rats.

Key words: brain ischemia-reperfusion, ginsenosides, protein aggregation, nimodipine