| Objective:As a major disease with high mortality and high mortality in the world,stroke is a disease that afflicts patients and imposes a heavy economic burden worldwide.The pathogenesis of cerebral ischemia-reperfusion injury is complex,and the oxidative stress injury is one of the main pathogenesis.Ginsenoside Rgl(G-Rgl)is extracted from natural Chinese herb ginseng,which has been shown the certain neuroprotective effects,but has little research on effect of anti-oxidative stress.This study was proposed the middle cerebral artery occlusion(MCAO)model in rats to applicate different dosese of G-Rgl to observe treatment effect,calculate cerebral infarction volume,detect the protein expression level of nuclear factor NF-E2-related factor 2(Nrf2),Kelch ECH associated protein 1(Keap1),Heme oxygenase-1(HO-1)and phosphorylated p38 mitogen activated protein kinases(p-p38MAPK)and the expression level of Nrf2,HO-1 in the microglia.Above all,this study is aimed to demonstrate the protective effect of ginsenoside Rgl on cerebral ischemia-reperfusion injury(CIR/I)in MCAO rats and investigate the role of G-Rg1 in the antioxidation and neuroprotective effects by regulating Nrf2/HO-1 signaling pathway.Methods:100 SPF grade Sprague-Dawley(SD)male rats(200 ± 20 g)were randomly divided into 5 groups:sham group,model group and G-Rgl treatment groups.①The MCAO model was duplicated by the line suppository method,and the treatment group was administered with G-Rgl 50 mg/kg,100 mg/kg,200 mg/kg abdominal cavity injection respectively 2 h after operation,and 3 d continuously for each day after the operation.②Each group of Rats were graded using Longa’s standard scoring method.③TTC dyeing was used to calculate the area of cerebral infarction in each group.④The expression levels of Nrf2,Keapl,HO-1 and p-p38 MAPK in the penumbral tissue were detected by Western Blot.⑤The expression of Nrf2 and HO-1 in microglia were monitored by immunofluorescence staining.Results:1.Longa’s neurological function scores:each group of rats were observated after 12 h,1 d,3 d,sham group rats were no neurologic deficits,activity is normal,model group and treatment group showed different degree of nerve function defect,score significantly higher than the sham group(P<0.05),treatment group rats nerve function defect score decreased significantly lower than the cerebral infarction group after 3 days medication(P<0.05).2.TTC staining result:there was a tiny white infarct area in the brain tissue section of the sham group,the area of cerebral infarction in each treatment group of G-Rgl was smaller than that in the model group,especially in the medium dose group(100 mg/kg)(P<0.05).3.Protein expression of Nrf2,Keap1,HO-1 and p-p38 MAPK:compared with the sham group,Nrf2 protein expression in model group significantly increased(P<0.05),moreover Nrf2 protein expression in the treatment group was higher than model group(P<0.05),medium dose group was most significant(P<0.01).Keap1,HO-1 protein expression trend was consistent with Nrf2.The content of p-p3 8 MAPK of the model group was significantly increased(P<0.05),compared with the sham group,the content of p-p38 in each treatment group was higher than the model group(P<0.05).4.Expression of Nrf2 and HO-1 in microglia:microglia in the cerebral cortex of the sham group were branched and the Nrf2 expression was weak;the model group and the treatment group presented amoeba-like activation status microglia,and the expression of Nrf2 in the cytoplasm of model group was significantly increased,and a little of nuclear translocations were observed.Compared with the model group,the expression of Nrf2 in microglia decreased in G-rgl treatment group,but the nuclear translocation was obvious.Compared with the sham group,the expression of HO-1 in the model group was increased,but it was lower than the G-rgl treatment group,and the expression of HO-1 was also seen in other cells.Conclusions:1.Ginsenoside Rgl can effectively improve the neurobehavioral function of MCAO rats and lower the score of neurologic function.2.Ginsenoside Rgl can reduce the cerebral infarction area significantly and alleviate brain tissue damage caused by ischemia reperfusion.3.Ginsenoside Rgl activates Keapl/Nrf2/HO-1 signaling pathway in microglia and plays a role of antioxidant neuroprotective effect. |
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