Effect of pioglitazone on white matter lesions and spatial memory function in chronic hypertensive rats / 国际脑血管病杂志

ABSTRACT

Objective To investigate the effect of peroxisome proliferator-activated receptor γ (PPARγ) agonist pioglitazone on white matter lesions and spatial memory function in chronic hypertensive rats.Methods Thirty-six male Sprague-Dawley rats were randomly divided into a sham operation group (n =6),a hypertensive group,(n =15),and a pinglitazone group (n =15).A model of stroke-prone renovascular hypertensive rat (RHRSP) was induced by the two-kidney two clip method in the hypertensive group and pioglitazone group.At 8 weeks after procedure,the rats were administered intragastrically.10 mg/(kg · d) pioglitazone was given in the pioglitazone group and an equal volume of saline was given in the hypertensive group.Blood pressure was monitored via caudal artery every 2 weeks before procedure,before administration,and after administration,respectively.After 12 weeks of continuous administration,Loyez staining was used to observe the degree of leukoaraiosis,and Morris water maze test was used to detect spatial memory function.Results After modeling,the blood pressure of RHRSP increased gradually.It was significantly higher than the sham operation group (all P =0.001).There was no significant difference in blood pressure between the hypertensive group and the pioglitazone group (P =0.897).The Morris water maze test showed that escape latencies of the sham operation group and the pioglitazone group were significantly shorter than the hypertensive group (all P ＜0.05).The numbers of crossing hidden platform in the 3 groups of rats were 5.200 ± 1.798,4.560 ± 1.592,and 2.333 ± 1.978 times,respectively.There were significantly differences (F =8.143,P =0.001).Both the sham operation group and the pioglitazone group were significantly more than the hypertensive group (all P ＜0.05).Loyez staining showed that the grades of white matter lesions in corpus callosum of the sham operation group,the hypertensive group,and the pioglitazone group were 0.333 ± 0.516,2.600 ± 0.507,and 0.500 ± 0.522,respectively.There were significantly differences among the 3 groups (F =25.652,P =0.000).The grade of the sham operation group and the pioglitazone group was significantly lower than the hypertensive group (all P＜ 0.05).Conclusions PPARγ agonist pioglitazone may protect the spatial memory function by relieving white matter lesions of the chronic hypertensive rats.