Role Of Diabetes Mellitus In The Pathogenic Process Of Ischemic Stroke And Its Possible Mechanism Of Deteriorate Ischemic Injury

Objective:To investigate the role of of diabetes mellitus in the pathogenic process of ischemic stroke and its possible mechanism of deteriorate ischemic injury.Methods:1.Clinical research:in this retrospective study,we analyze the role of lipids and carotid artery plaque in the pathogenic process of ischemic stroke with diabetes mellitus,and the distribution of infarction impacted by diabetes mellitus.2.Basic research:the change of PGC-1? was detected during the course of ischemic stroke,and its role and possible pathway were studied through relative intervention.Based on this background,we next study its change and role in the individuals of ischemic stroke with diabetes mellitus.Results:1.The relative risk between ischemic stroke and diabetes mellitus was 2.256(95%CI=1.242-4.095)and 2.105(95%CI=1.066-4.157)adjusted by ordinary risk factors,both the results were P<0.05,while the carotid artery plaque was added in procedure of adjustment,the result was P>0.05(OR(95%CI)was 1.696(0.833-3.452).2.It is lower of HDL-C in the group of diabetes mellitus compared to the group of non-diabetes mellitus(1.050 ± 0.319mmo1/1 vs 1.157±0.322mmol/l,P=0.001).3.HDL-C was correlated to plaque information with OR(95%CI,P value)was 0.416(0.210-0.823,0.012)through logistic regression,while there has no correlation between plaque information and other subtype of blood lipids.3.The level of high density lipoprotein(HDL)cholesterol was decreased obviously in the DM group compared to the non-DM group and low level of HDL cholesterol was prevalent in the AIS patients with DM.logistic regression demonstrated that decreased HDL cholesterol was correlated to the AIS with DM,not all AIS,and the relative risk of ischemic stroke in low HDL cholesterol level group was 2.113(95%CI= 1.191-3.749,P=0.011)compared to the high level group.Furthermore,age has the obviously impact on it.HDL cholesterol was correlated to the AIS with DM just in the populations of aged? 70 years(OR=0.192,P=0.000),low level of HDL cholesterol had more high risk of ischemic stroke than that in the high level group(OR=6.818,P=0.002).4.Posterior infarction was correlated to diabetes,with the value of R and P was 0.176 and 0.000.Logistic regression between posterior infarction and diabetes demonstrated that OR(95%CI)was 2.247(1.551-3.257),it changed to 1.898(1.213-2.968)when adjusted by relative risk factors,and both of the P value were below 0.05.5.More PGC-1? expression was found in the OGD neurons compared with normal group.Overexpre-ssion of PGC-1? suppressed cell apoptosis while inhibition of the PGC-1?expression induced cell apoptosis in OGD neurons.Furthermore,increase of PGC-1?resulted in activation of NMDA receptor,p38 and ERK MAPK pathway.Block of NMDA receptor by its antagonists MK-801 reduced PGC-1? mRNA expression in OGD neurons,while NMDA itself can directely induced the expression of PGC-1? in neuronal cell.At the same time,PD98059(ERK MAPK inhibitor)and SB203580(P38 MAPK inhibitor)also prevented the upregulation of PGC-1? in OGD neurons and MK801 can inhibit the expression of P38 and ERK MAPK.6.Exacerbated brain damage was obviously in diabetic mice subjected to focal ischemia compared to the wild type mice,so did the decrease of PGC-1?,and atorvastatin can reverse its expression effectively.Also,ANG-1,ANG-2,VEGF and JNK have the same trend.Conclusions:1.Diabetes mellitus play the important role in the formation of carotid artery plaque through lipids,which will influence the occurrence of ischemic stoke.2.Decreased PGC-1? induced the exacerbated brain damage of ischemic stroke caused by diabetes mellitus.