Abstract:

Objective
To study the effect of peroxisome proliferators-activated receptor-γ(PPAR-γ) ligands rosiglitazone(RSG) on focal cerebral ischemia injury   in type 2 diabetic(T2DM) rats from the endoplasmic reticulum stress（ERS） perspectives and to clarify its mechanism.Methods 72 male SD rats were fed with high amounts of sugars and fats for 4 weeks,then the low -dose STZ (25.0 mg/kg) was injected into caudal vein to make T2DM rat models, the  model rats were divided into four groups randomly:sham operation group(n=18),control group(n=18),RSG group(n=18) and RSG+GW9662 group(n=18).The MCAO models were made after the rats in each group were pretreated by drugs.The surgical procedure in sham operation group was the same as the above,but no thread inserted.The rats were executed  24 h after cerebral ischemia,the neuroethology evaluations for  the rats in each group   were made,and the  pathomorphology of brain tissue in rats  was  observed by HE staining,the expressions of glucose-regulated protein 78 （GRP78） and C/EBP homologous protein （CHOP）were detected by immunohistochemical and Western blotting,and the expressions of GRP78 mRNA and CHOP mRNA were detected by RT-PCR.Results  The nerve function defect after cerebral ischemia improved obviously in RSG group compared with control group(P<0.01);there were no statistically significant differences between RSG+GW9662 group and control group(P>0.05).The GRP78 expression in RSG group was higher than that in control group(P<0.05),however,the CHOP expression in RSG group was lower than that in control group (P<0.05)；RSG+GW9662 group showed opposite trend compared with RSG group.Conclusion PPAR-γ agonist RSG has the protective effect on focal cerebral ischemia injury  of T2DM rats and the mechanism may be related with up-regulating  the   GRP78 expression and  decreasing  the CHOP expression.

Key words: words：peroxisome prolifer ators-activated receptor-γ;endoplasmic reticulum stress;rosilglitazone;cerebral ischemia;type 2 diabetes