Therapeutic effect of intraperitoneal injection of total flavonoids from trollius chinensis on cerebral ischemia-reperfusion injury in rats and its mechanism
Objective To observe the therapeutic effect of intraperitoneal injection of total flavonoids from trollius chinensis on cerebral ischemia-reperfusion injury in rats and to explore its mechanism.Methods Male SD rats were ran-domly divided into the sham operation group,middle cerebral artery occlusion(MCAO)group,total flavonoids from trolli-us chinensis group,and ferroptosis inhibitor group,with 18 rats in each group.Except for the sham operation group,we used the thread-embolization method to make the rat MCAO models in other groups;the surgical procedures of the sham op-eration group was basically the same as that of the model group but the wire-bolt was not inserted.Rats in the total flavo-noids from trollius chinensis group and the ferroptosis inhibitor group were intraperitoneally injected with total flavonoids from trollius chinensis and the ferroptosis inhibitor Lip-1,respectively;rats in the sham operation group and the model group were injected with the equal volume of normal saline intraperitoneally,and the drugs were administered once a day,and for 3 consecutive days.The Longa scoring method was used to score the neurological deficits in rats.TTC staining was used to calculate the percentage of infarcted brain tissue.Colorimetric analysis was used to detect oxidative stress indica-tors such as reactive oxygen species(ROS),malondialdehyde(MDA),and glutathione peroxidase(GSH-Px)in the brain tissues.Western blotting was used to detect the ferroptosis-related proteins glutathione peroxidase 4(GPX4),long-chain acyl CoA synthase(ACSL4),transferrin receptor 1(TFR1),and membrane iron transporter-1(Ferroportin-1)in the brain tissues.Results Neurological deficit score and the percentage of cerebral infarction volume were as follows:MCAO group>total flavonoids from trollius chinensis group,ferroptosis inhibitor group>sham operation group(all P<0.05).The content of ROS and MDA in the brain tissues was as follows:MCAO group>total flavonoids from trollius chi-nensis group,ferroptosis inhibitor group>sham operation group,and the GSH-Px content was in the following order:sham operation group>total flavonoids from trollius chinensis group,ferroptosis inhibitor group group>MCAO group(all P<0.05).The protein expression of GPX4,TFR1,and ferroportin-1 was as follows:MCAO group<total flavonoids from trollius chinensis group,ferroptosis inhibitor group,and sham operation group,and the ACSL4 protein expression was as follows:MCAO group>total flavonoids from trollius chinensis group,ferroptosis inhibitor group,and sham operation group(all P<0.05).Conclusion Intraperitoneal injection of total flavonoids from trollius chinensis has certain thera-peutic effect on cerebral ischemia-reperfusion injury in rats,and the mechanism may be related to the inhibition of ferroptosis.
total flavonoids from Trollius chinensisischemia-reperfusion injurycerebral ischemiaferroptosisoxidative stress