Effect and mechanism reserch of Gabexate on cerebral ischemia reperfusion injury in rats
QIAO Jianxin1 LIU Xipeng1 LIU Ming1 WANG Jinghui1 GUAN Chaonan2
1.Department of Neurosurgery, the First Affiliated Hospital of Hebei North University, Hebei Province, Zhangjiakou 075000, China;
2.Department of Nuclear Medicine, the First Affiliated Hospital of Hebei North University, Hebei Province, Zhangjiakou 075000, China
Abstract：Objective To explore the effect and mechanism of Gabexate on cerebral ischemia reperfusion injury in rats. Methods A total of 125 experimental rats were selected to establish focal cerebral ischemia reperfusion model by modified thread occlusion method. All rats were divided into sham operation group, model group and Gabexate high, medium and low dose groups according to random number table method, with 25 rats in each group. Low, medium and high dose Gabexate groups were intervened by intraperitoneal injection of 25, 50 and 75 mg Gabexate, respectively. Sham operation group and model group were given the same volume of normal saline. The rats in each group were scored by blind method. The pathological changes of brain tissue and the apoptosis of nerve cells were observed. The activities of antioxidant enzymes, malondialdehyde (MDA), inflammatory factors, apoptosis related gene expression and related protein expression in brain tissue were determined. Results The neurological deficit score, glutathione peroxidase (GSH-Px), B cell lymphoma factor 2 (bcl-2) mRNA and nuclear factor kappa B (NF-κB) in model group were lower than those in sham operation group, the apoptosis rate of nerve cells, MDA, superoxide dismutase (SOD), catalase (CAT), tumor necrosis factor α (TNF-α), interleukin (IL)-1β, IL-6, water soluble protein (Bax) mRNA, caspase-3 and NF-κB in model group were higher than those in sham operation group, the differences were statistically significant (P < 0.05). The neurological deficit score, MDA, SOD, bcl-2 mRNA and NF-κB in medium and high dose Gabexate groups were higher than those in low dose Gabexate group, the apoptosis rate, GSH-Px, CAT, TNF-α, IL-1β, IL-6, Bax mRNA, caspase-3 and NF-κB of medium and high dose Gabexate groups were lower than those of low dose Gabexate group, the differences were statistically significant (P < 0.05). The scores of neurological deficit, MDA, SOD, bcl-2 mRNA and NF-κB in high dose Gabexate group were higher than those in medium dose Gabexate group, the apoptosis rate, GSH-Px, CAT, TNF-α, IL-1β, IL-6, Bax mRNA, caspase-3 and NF-κB of high dose Gabexate group were lower than those of medium dose Gabexate group, the differences were statistically significant (P < 0.05). The neurological deficit score, MDA, SOD, bcl-2 mRNA and NF-κB in Gabexate low, medium and high dose groups were higher than those in model group, the apoptosis rate of nerve cells, CAT, TNF-α, IL-1β, IL-6, Bax mRNA, caspase-3 and NF-κB in Gabexate low, medium and high dose groups were lower than those in model group, the differences were statistically significant (P < 0.05). The level of GSH-Px in Gabexate low dose group was higher than that in model group, and the levels of GSH-Px in Gabexate middle and high dose groups were lower than those in model group, the differences were statistically significant (P < 0.05). Conclusion Gabexate can effectively reduce the pathological damage caused by cerebral ischemia reperfusion in rats, inhibit lipid oxidation reaction after reperfusion, play a protective role, and reduce the damage caused by inflammatory reaction. The above effects may be caused by inhibiting NF-κB signal pathway and increasing the activity of antioxidant enzymes, so as to reduce the inflammatory injury of brain tissue and the apoptosis of nerve cells.
2021, Vol. 18 
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