Protecive Effects Of Pioglitazone On Focal Cerebral Ishemia-reperfusion Injury In Rat And The Levels Of Il-6

Objective To investigate whether the PPAR gamma ligand pioglitazone (PGZ) acting as a peroxisome proliferator-activated receptorγagonist (PPARγ) inhibited focal brain ischemia-reperfusion injury and study its effects on blood and brain level of interleukin -6(IL-6), and to explore whether the protective role of PGZ on focal brain ischemia-reperfusion injury is related to the content of the IL-6.Methods A total of 100 adult male SD rat underwent 2h middle cerebral artery occlusion followed by a 22h reperfusion (MCAO/R) were randomly divided into sham group, I/R+NS group, I/R+ PGZ high-dose group (15mg/kg) and I/R+ PGZ low-dose group (10mg/kg). The pioglitazone pretreament group was fed Pioglitazone at 3d and 1h before ischemia and I/R+NS group was fed equal amounts of saline water. 22h After MCAO/R, we investigated the following indicators. The neurological scores were made according to Zea Longa scale. 2, 3, 5 - triphenyl tetrazolium chloride (TTC) staining was adopted to determine the volume of cerebral infarction. The content of IL-6 was measured in ischemic brain and serum by using ELISA. At the same time, pathological change was observed by HE staining and Nissl staining. Results Neurological function score was significantly decreased in the pioglitazone pretreament group compared with those in the I/R+NS group, I/R+ PGZ high-dose group (15mg/kg) and I/R+ PGZ low-dose group(10mg/kg) were decreased by 46.1% and 30.7 % respectively ( P <0.01). Pioglitazone reduced cerebral infarction volume in rats (P <0.01), which was more predominant in I/R+ PGZ high-dose group compared with I/R+ PGZ low-dose group (P <0.05). The levels of IL-6 in ischemic brain and serum in the I/R+NS group were lower that in the sham operated group (P <0.01) and higher than that in I/R+PGZ high-dose group (15mg/kg) and I/R+PGZ low-dose group (10mg/kg)(P <0.05), it was more lower in R+ PGZ high-dose group compared with I/R+ PGZ low-dose group (P <0.05) , and the brain cell morphology in PGZ pretreatment group recover better than I/R+NS group.Conclusions Pioglitazone has the protective effect on focal cerebral ischemia /reperfusion injury in rats in dose-dependent manner, the protective role of pioglitazone on focal cerebral ischemia /reperfusion injury in rats is related to the reduce the content of the IL-6.