| Objective: To observe the effect of PPAR gamma (peroxisome proliferator activated receptor )agonist pioglitazone pretreatment on myocardial ischemia reperfusion myocardial apoptosis andon the expression of GRP78 and Caspase-12 proteins in rats.so as to explore the the endoplasmicreticulun stress signaling pathways for pioglitazone in protection of m yocardium.Methods: male Wistar rats, the ordinary diet feeding. Weight 170-230g, were randomly dividedinto sham operation group, the I / R group and pioglitazone preconditioning group. pioglitazonepreconditioning group was further divided into 3 groups, were infused orally with pioglitazonein , 3mg/kg.d 10mg/kg.d 20mg/kg.d soluble in 2ml saline gavage and sham operation group andI/R group were infused orally with 0.9%sodium chloride solution,2ml/d, a total of 7 days. Theischemia/reperfusion injury rats models were produced: tracheal intubation using animalventilator breathing, electrocardiogram, ligation of the anterior descending coronary artery30min,reperfusion 2h. Modeling success after abdominal aortic blood sampling, centrifugal,separation of serum, using automatic biochemical analyzer detection of serum LDH, CK levels;cardiac, clean blood, take the left ventricular forearm, embedding, sectioning, using TUNEL( ISEL ) staining for detection of apoptosis in myocardial cells of several groups, using SABC( streptoavidin - peroxidase ) Immunohistochemistry Assay for detection of GRP78 andcaspase-12 protein expression, and the expression of semi quantitative analysis.Results: 1 rats in I / R serum ,the level of LDH, CK were significantly higher than that in thesham operation group ( P < 0.05 ), different doses of pioglitazone pretreatment serum LDH, CKlevels were significantly lower thanI / R group ( P < 0.05 ), but the effects of pioglitazone ingroup 3mg and group 10mg showed no obvious difference ( P > 0.05 ). 2 the myocardial cellapoptosis index in I / R group increased significantly than in the sham operation group ( P <0.05 ). pioglitazone pretreatment groups apoptosis index is better than that of I / R groupdecreased significantly ( P < 0.05 ), pioglitazone 3mg group and 10mg group showed nosignificant difference ( P > 0.05 ). 3 in myocardial tissues of I / R，the expression of caspase-12,GRP78 protein was significantly elevated compared with the sham operation group ( P < 0.05 ),rats given pioglitazone preconditioning, to make model of ischemia reperfusion, 3 doses ofpioglitazone preconditioning group reduced myocardial cell protein GRP78 and caspase-12expression significantly than I / R group（p<0.05）, but pioglitazone 3mg group and 10mg groupshowed no significant difference ( P > 0.05 ).Conclusion: Pretreatment with pioglitazone could be play a protective role on myocardialischemia-reperfusion injury in rats,which may be related to inhibit the expression of GRP78、 Caspase-12protein, reduce the endoplasmic reticulum stress-related apoptosis. and The higherdose has more significant effect. |
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