Cerebral protective effect of Duzhi pills on ischemic stroke rats and its mechanisms
10.16781/j.CN31-2187/R.20230253
- VernacularTitle:杜蛭丸对缺血性脑卒中大鼠的脑保护作用及其机制
- Author:
Huihao WANG
1
;
Qing LIU
;
Wei XIE
;
Li LIU
;
Zhiyong WANG
Author Information
1. 中国医药工业研究总院先导物成药性研究全国重点实验室,上海 200437
- Keywords:
Duzhi pills;
ischemic stroke;
inflammatory cytokines;
fibrinogen;
antioxidation
- From:
Academic Journal of Naval Medical University
2025;46(5):602-608
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the cerebral protective role of Duzhi pills on ischemic stroke rats and its mechanisms.Methods The healthy male SD rats were assigned to 5 groups:sham group,model group,Duzhi pill low-dose group(1.0 g/kg a day),Duzhi pill high-dose group(2.0 g/kg a day),or argatroban group(positive control).The low-dose and high-dose groups of Duzhi pills were intragastrically administered once a day for 8 d,while the other groups were intragastrically administered with the same amount of normal saline.Except the sham group,the middle cerebral artery occlusion(MCAO)cerebral ischemia-reperfusion model was established by suture method at 0.5 h after intragastric administration on the 8th day in other groups,and the ischemia duration was 90 min.Argatroban group was given a single dose(3.0 mg/kg)of argatroban via caudal vein at the same time of reperfusion.After 24 h of cerebral ischemia,the area of cerebral infarction,degree of cerebral infarction and neurological function injury were evaluated by 2,3,5-triphenyltetrazolium chloride(TTC)staining,Nissl staining and neurobehavioral score,respectively.The levels of inflammatory factors(transforming growth factor-β1[TGF-β1]and interleukin-1β[IL-1β])in the brain after cerebral ischemia were detected by enzyme-linked immunosorbent assay(ELISA),and the coagulation indexes were detected by an automatic coagulation analyzer.The scavenging ability of Duzhi pills on free radicals was analyzed by 2,2-diphenyl-1-picrylhydrazyl(DPPH)scavenging experiment.Results High-dose Duzhi pills reduced the cerebral infarction area,decreased the deep Nissl staining score of neural cells,and improved the symptoms of neurobehavioral defects in MCAO rats(compared with the model group,all P<0.01).The levels of IL-1β and TGF-β1 in the ischemic brain tissue of the model group were significantly increased(compared with the sham group,both P<0.01),while the levels of IL-1β and TGF-β1 in the brain tissue of the rats treated with low-dose and high-dose Duzhi pills were significantly decreased(compared with the model group,all P<0.01).The coagulation index fibrinogen level in the model group was significantly higher than that in the sham group(P<0.01),and both low-dose and high-dose Duzhi pills could inhibit the production of fibrinogen(compared with the model group,both P<0.01).DPPH scavenging test results showed that Duzhi pills could scavenge free radical,the half inhibitory concentration was(1.33±1.11)mg/mL,and the slope of the curve was 1.378±0.145.Conclusion Duzhi pills play a cerebral protective role in ischemic stroke rats.The mechanism may be related to the inhibition of fibrinogen production,the reduction of inflammatory factors(TGF-β1 and IL-1β),and the antioxidant effects.