The regulation of ischemic postconditioning on metabolic disorders of type 2 diabetes mellitus combined with cerebral ischemia in tree shrews / 中华内分泌代谢杂志

ABSTRACT

Objective To establish tree shrew model of type 2 diabetes mellitus (T2DM) combined with cerebral ischemia (IS),and to explore the regulatory mechanism of ischemic postconditioning (PC) on gene differential expression in cerebral cortex under metabolic abnormalities and cerebral ischemia condition.Methods Seventy tree shrews were divided into control,T2DM,IS,T2DM+IS and T2DM +IS +PC groups (n =14 each group).The experimental diabetes model was established by the combined use of high fat diet breeding with streptozocin injection in tree shrew.The local cerebral thrombosis was induced by photochemical reaction in tree shrews,and ischemic PC was established at 4h after cerebral ischemia followed by clipped ipsilateral common carotid artery three times (5 min/time).The metabolic status of tree shrews was measured by serum biochemical markers.TTC staining,HE staining,and electron microscopy were used to observe the changes of the body's metabolic status at 24h after IS.RNA-seq was used to analyze differentially expressed genes.Results The ultrastructure of brain cells was abnormal and the cerebral infarction area was the largest in T2DM+IS tree shrews (P＜0.01).Compared with control group,body weight of tree shrews in T2DM + IS group was significantly reduced (P＜ 0.01) while blood glucose,total cholesterol,low density lipoprotein-cholesterol,triglyceride,and C-reactive protein (CRP) levels were markedly increased(all P＜0.01).The RNA-seq analysis showed that there were 1 629 differentially expressed genes (1 109 up-regulated genes and 520 down-regulated genes) in T2DM + IS group vs control group.However,ischemic PC deceased the cortical infarction area (P＜0.01)and reduced blood glucose,lipid and CRP levels (P＜0.05),with 520 differential expression genes (203 up-regulated genes and 317 down-regulated genes).Conclusion Ischemic PC improves the metabolic disturbance-aggravated ischemic brain injury in T2DM tree shrews,which may be related to its regulation on gene expression in cerebral cortex.