Effect of Pioglitazone, a Peroxisome Proliferator-Activated Receptor Gamma Agonist, on Ischemia-Reperfusion Injury in Rats

Abstract

Two groups of rats were used to examine the effect of pioglitazone, a peroxisome proliferator-activated receptor γ (PPARγ) agonist, on rat hearts using an in vivo model of ischemia-reperfusion (I/R) to elucidate potential mechanisms. One group was the 30-min reperfusion group, which was further subdivided into sham (n = 5), vehicle (n = 6) and pioglitazone (3 mg·kg^–1, n = 7) treatment groups with 30 min ischemia followed by 30 min reperfusion to detect data related to cardiac function and the area of myocardial infarction. The other group was the 120-min reperfusion group, subdivided into sham (n = 5), vehicle (n = 6), and pioglitazone 0.3 mg·kg^–1 (n = 6), 1 mg·kg^–1 (n = 7) and 3 mg·kg^–1 (n = 6) treatment groups. Immunohistochemistry, in situ hybridization, terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) and DNA agarose gel electrophoresis were performed to detect apoptosis and expressions of Bax, Bcl-2, caspase 3, MMP-2 and PPARγ protein, and MMP-2 and PPARγ mRNA. We found that, after acute treatment with pioglitazone, the ratio of necrosis to area at risk decreased by 28% (p < 0.01) and that of necrosis to left ventricle was reduced by 32% (p < 0.01), compared with the vehicle group. Heart rate and +dp/dt_max, representing the cardiac systolic function, as well as –dp/dt_max, the indicator of cardiac diastolic function, improved significantly at 1 and 30 min after reperfusion (p < 0.05–0.01). Furthermore, myocardial apoptosis was significantly suppressed by acute treatment with pioglitazone as evidenced by the decreased number of TUNEL-positive myocytes and DNA ladder, enhanced Bcl-2 protein expression, reduced Bax and caspase 3 protein expression in a dose-dependent manner compared with vehicle-treated rats. In addition, acute treatment with pioglitazone dose-dependently increased PPARγ expression and decreased MMP-2 expression at protein and mRNA levels. Our findings demonstrate that a PPARγ agonist may protect the heart from I/R injury. The protective effect is likely to occur by reducing cardiomyocyte apoptosis and inhibiting MMP-2.

Effects of infrasound at 8�Hz 90�dB/130�dB on NMDAR1 expression and changes in intracellular calcium ion concentration in the hippocampus of rats

“…cao et al reported that there was high expression of the metabolic glutamic acid receptor mGlur1α on days 1 and 7 in rats exposed to ultrasound at 8 Hz 130 dB 2 h/day. The expression of mGlur1α was found to return to normal levels on day 14 (17). This suggests that notable changes occur in hippocampal Glu and its receptor upon exposure to infrasound at 8 Hz 120-130 dB applied daily for 2 h. regarding the effect of 8 Hz 130 dB infrasound on the increase in ca 2+ concentration, it was demonstrated that not only the ion glutamic acid receptor (iGlur), but also the metabolic glutamic acid receptor (mGlur), participated in its increase.…”

“…in this case, the effect on the increase in ca 2+ concentration was mainly mediated by mGlur1. infrasound at 8 Hz 130 dB was found to have an inhibitory effect on nMdar1 and mGlur1 expression on day 14; this coincided with a ca 2+ overload symptom, accompanying distinct damage in the ultramicroscopic structure of the cells, such as mitochondrial swelling and pyknosis (1,17). This indicates that the effect of 8 Hz 130 dB infrasound on day 14 directly resulted in damage to the structure of the cell membrane and the opening of various types of calcium channels, thus enabling extracellular ca 2+ to flow inwards and Ca…”

Peroxisome Proliferator-Activated Receptor-γ as a Potential Therapeutic Target in the Treatment of Preeclampsia

“…In models of diabetes mellitus and cardiovascular disease, activation of PPAR-␥ has been shown to restore vascular structure and correct endothelial dysfunction, [17][18][19] resulting in a reduction in the elevated blood pressure associated with hypertensive conditions. 20 -22 In the present study, administration of the PPAR-␥ agonist rosiglitazone to RUPP rats ameliorated both hypertension and endothelial dysfunction via a HO-1-dependent pathway.…”

Pioglitazone attenuates myocardial ischemia-reperfusion injury via up-regulation of ERK and COX-2

“…Considerable evidence indicates that apoptosis is a significant contributor to myocardial cell death after I/R, particularly during the early stages (1). Studies suggest that targeting the reperfusion-induced apoptotic component of cell death can affect the apoptotic and necrotic components of cell death, the consequences of which are a reduction in infarct size and improved contractile function.…”

“…Our previous study demonstrated that the peroxisome proliferator-activated receptor (PPAR) γ agonist, pioglitazone (PIO), may protect the heart from I/R injury; the protective effect is likely to occur by inhibiting cardiomyocyte apoptosis (1). PPARs are nuclear hormone receptors that stimulate transcription of specific genes by binding to specific DNA sequences after activation by an appropriate ligand.…”