Protective Effects Of Chrysophanol Liposomes On Cerebral Ischemia And Reperfusion Injury In Mice

Ischemic cerebrovascular disease (ICVD) is a type of diseases that is harm to human health with high prevalence, morbidity and mortality. At present, a lot of researches have been done on the active ingredient of natural medicine in the treatment of cerebrovascular disease in recent years.Chrysophanol (Chry) is one of the anthraquinone compounds. By our previous researches, its action on improving memory impairment and anti-hypoxia ability were demonstrated. However, because of its lower solubility, instability nature and gastrointestinal irritation, the further application is limited. The chrysophanol liposome with high bioavailability has been prepared by our research group. The experiments showed that chrysophanol liposome could obviously improve the memory disorder caused by cerebral ischemia and reperfusion injury.This project aims to confirm the action of chrysophanol liposomes on protecting hippocampal neurons against the damage after cerebral ischemia and reperfusion from the morphology point of view, and further explore the protective mechanism.275male mice were randomly divided into11groups:normal control group, sham-operated group, cerebral ischemia and reperfusion injury model group, and the solvent control group of N, N-dimethylformamide (DMF) and liposomes, chrysophanol group (10.0,1.0,0.1mg·kg-1), chrysophanol liposomes group (10.0,1.0,0.1mg·kg-1). After d14, the relevant indexes of the brain tissue were determined.1The influences of chrysophanol liposomes on neurological severity score(NSS) and infarct area after cerebral ischemia and reperfusion Compared with sham-operated controls, the deficits of neural function in the model group was increased markedly after d7and d14(P<0.05) Compared with the same chrysophanol group, the neural symptoms were improved and the infarcted area was significantly reduced in liposomes group (10.0mg·kg-1) after d14(P<0.05)2The influences of chrysophanol liposomes on patho morphology and the ultras tructure pathology of hippocampal neurons after cerebral ischemia and reperfusionNormal control group and sham-operated group had normal cellular structure. In the model group the majority of cell structure were damaged. The nucleus became shrinking, and mitochondria swelling with cristae broken. There were relatively complete cell structure, slightly pyknotic nuclei, minor injury to mitochondria and a majority of mitochondria were normal in the chrysophanol liposomes group (10.0mg·kg-1).3The effects of chrysophanol liposomes on expression of caspase-3, Bax and Bel-2after cerebral ischemia and reperfusion in hippocamalCompared with sham-operated group, caspase-3, Bax and Bcl-2expression in the model group were significantly increased (P<0.05) Compared with the same chrysophanol group, chrysophanol liposomes group (10.0mg·kg-1) was significantly better (P<0.05)4The effects of chrysophanol liposomes on expression of BDNF and GFAP after cerebral ischemia and reperfusion in hippocamalCompared with sham-operated group, The BDNF and GFAP expression in the model group were significantly different,(P<0.05) Compared with sham-operated group, chrysophanol liposomes group (10.0mg·kg-1) was significantly better (P<0.05).All results show that the chrysophanol liposomes can significantly improve neural function and ultrastructural pathological injury, increase BDNF expression, inhibit astrocyte activation, and regulate caspase-3, Bax and Bcl-2expression after cerebral ischemia and reperfusion injury. The chrysophanol liposomes is expected for the treatment of ischemic cerebrovascular disease clinically.