Effect Of Leptin On Focal Cerebral Ischemia Injury In Rats And Its Mechanism

Background: Stroke is the second leading cause of death worldwide,and the most common cause of permanent disability worldwide,according to the WHO.600 died of stroke every year all over the world,which is 80% of ischemic stroke.In China,the prevalence of stroke was about 1.88%,which was significantly higher than that of the cooperative group of cerebrovascular disease epidemiology in 1986(the prevalence rate was 0.27%).In recent years,the prevalence of stroke in China has been rising.At present,cerebrovascular disease has become the leading cause of death among residents in China,and the incidence of ischemic stroke is increasing at an annual rate of 8.7%.Leptin is a polypeptide hormone secreted mainly by adipose cells.It is encoded by the obese gene and its molecular weight is 16 KD,which can be combined with the receptor in the hypothalamus to produce the physiological function of inhibiting food intake and controlling body weight.In recent years,the results show that leptin may play a positive role in the protection of brain cells,and can significantly reduce the brain cell death induced by ischemia and hypoxia,and reduce the infarct size.At present,foreign influence on leptin in the study reported protective effect on cerebral ischemic stroke mainly focused on the nuclear expression regulation role of leptin in stroke and domestic animalexperiments are rarely reported.Some studies have shown that leptin can be used as a potential treatment for ischemic cerebrovascular disease.Objective:To observe the effect of leptin on focal cerebral ischemia in rats,and to explore the possible mechanism of its protective effect on cerebral ischemia.Methods:Male SD rats were randomly assigned in accordance with the principle of randomly assigned to 4 groups,sham operation group,model group,treatment group,leptin leptin +ERK1/2 inhibitor(PD98059)treatment group,SD male rat model of middle cerebral artery ischemia by using suture method(MCAO).Objective To observe the effect of leptin on the focal cerebral ischemia injury in ERK1/2 signaling pathway in rats.Result:1.Leptin reduced neurological deficit,but did not affect body weight change.2.leptin reduced infarct volume and brain edema.3.Leptin increased the expression of p-ERK1/2 in focal cerebral ischemia in rats and expressed more in the ischemic penumbra.4.PD98059 inhibitor could inhibit the expression of p-ERK1/2.Conclusions:In the rat model of middle cerebral artery(MCAO),it was found that leptin could promote the expression of ERK1/2 phosphorylation in the ischemic penumbra and the ischemic core,which was further aggravated by ischemia.Leptin has protective effects on ischemic penumbra,and its protective mechanism is through the activation of ERK1/2 signaling pathway.By activating the ERK1/2 signaling pathway to reduce brain edema,reduce cerebral infarction volume,reduce ischemic brain damage,improve neurological defects.