Effects of irbesartan on Notch1 signaling pathway in diabetic rats with myocardial injury / 中国应用生理学杂志

OBJECTIVE@#To investigate the effects and mechanisms of irbesartan on myocardial injury in diabetic rats, and to analyze the changes of Notch1 signaling pathway in it.@*METHODS@#Thirty rats were randomly divided into four groups:normal control group (CON, =6), high calorie group (HC, =6) and diabetes mellitus group (DM, =9), irbesartan + diabetes group (Ir + DM, =9). After modeling 8 weeks later, the body weight ratio and left ventricular weight index were measured and the serum levels of triglyceride (TG) and total cholesterol (TC) were measured by automatic biochemical analyzer. The changes of superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in myocardium of rats were determined by the kit and the expressions of B-cell lymphoma-2 (Bcl-2) and Bcl-2 assaciated X protein (Bax) protein in myocardium were detected by immunohistochemistry. The expressions of Notch1, Hes-1 and jagged-1 in myocardium of rats were detected by Western blot.@*RESULTS@#Compared with CON group, the levels of heart weight/body weight (H/B), left ventricular weight index(LVWI) and fasting blood glucose(FBG) in HC group were not significantly changed, while the levels of blood lipids, MDA and Bax were increased significantly, and the expressions of SOD, Bcl-2 and Notch1, Hes-1 and Jagged-1 were decreased. Compared with HC group, the levels of H/B, LVWI, FBG, MDA and Bax in DM group were increased significantly, and the levels of SOD, Bcl-2 and Notch1, Hes-1 and Jagged-1 were decreased. The expression of H/B, LVWI, Notch1, Hes-1 and Jagged-1 in Ir+DM group were increased, but there was no significant difference between the other indexes. The H/B and LVWI in Ir + DM group were significantly lower than those in DM group, the levels of blood lipid and blood glucose did not change significantly, but the incidence of oxidative stress and apoptosis was reduced. While Notch1, Hes-1, Jagged -1 protein expressions were increased.@*CONCLUSIONS@#Diabetes can induce myocardial injury, and irbesartan has myocardial protective effects through activation of Notch1.

Effects of simvastatin on aortic vascular endothelial cell apoptosis and Bcl-2 protein expression in a rat model of atherosclerosis / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the effects of simvastatin on vascular endothelial cell apoptosis and Bcl-2 protein expression in the aorta in a rat model of atherosclerosis.</p><p><b>METHODS</b>Thirty-six rats were randomized into control group (n=10), atherosclerosis model group (n=13) and simvastatin intervention group (n=13). In the latter two groups, rat models of atherosclerosis were established by intraperitoneal injection of vitamin D3 combined with high-fat feeding for 6 weeks, and the control rats were fed with regular diet. In the intervention group, the rats were further fed with high-fat diet with daily simvastatin treatment for 4 weeks. After the treatments, the pathological changes and plaque in the thoracic aorta were observed, and the expression of Bcl-2 protein was detected with immunohistochemistry. TUNEL assay was used to determine the apoptosis index (AI) of the vascular endothelial cells.</p><p><b>RESULTS</b>Compared with that in the control group, Bcl-2 protein expression in the aorta of atherosclerotic rats was significantly decreased (P<0.05); simvastatin treatment obviously increased the expression of Bcl-2 protein in atherosclerotic rats (P<0.05) to a level similar to that in the control group. The AI was the highest in the model group (P<0.05) and comparable between the control and simvastatin treatment group.</p><p><b>CONCLUSION</b>The therapeutic effect of simvastatin against atherosclerosis is probably mediated by up-regulation of Bcl-2 protein, which inhibits vascular endothelial cell apoptosis in rats with aortic atherosclerosis.</p>

Correlation between cytochrome 3A4+894C>T P450 gene polymorphism and outcomes of coronary intervention in patients with acute coronary syndrome / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the relationship between plasma cytochrome P450 3A4 (CYP3A4) 894C>T gene polymorphism and the risk of recurrence of adverse cardiac events after percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS).</p><p><b>METHODS</b>A total of 275 patients with ACS received standard dual antiplatelet therapy and PCI. Platelet aggregation rate (PAR) was detected in each patient before and 7 days after administration of the anti-platelet drugs. Single nucleotide polymorphism of CYP3A4 gene 894C>T was detected with PCR and microarray technique. The number of coronary artery lesions was determined by PCI and the Gensini score was calculated. The patients were followed up for 3-12 months after discharge.</p><p><b>RESULTS</b>No significant difference was found in CYP3A4 gene polymorphism between patients with clopidogrel resistance (CR group) and those without CR (NCR group) (P>0.05). Multivariate logistic regression analysis showed that CYP3A4 gene 894C>T polymorphism was not correlated with CR in patients with ACS (OR 1.359, P>0.05). During the follow-up, the incidence of cardiovascular events was significantly higher in CR group than in NCR group (P<0.05), but this difference was not related to the mutation type of 894C>T locus of CYP3A4 gene.</p><p><b>CONCLUSION</b>The CYP3A4 gene 894C>T polymorphism is not associated with the effect of anti-platelet therapy and the risk of cardiovascular event in patients with ACS following PCI.</p>

Effects of activation of ALDH2 by ethanol on the expression of JNK in kidney of diabetic rats / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To observe the effect of activation of aldehyde dehydrogenase 2 (ALDH2) by ethanol on the expression of c-Jun N-terminal kinase (JNK) in the kidney of diabetic rats.</p><p><b>METHODS</b>Eightheen healthy male SD rats were randomly divided into 3 groups (n = 6): normal control group, diabetes group and ethanol + diabetes group. After 8 weeks, 24 h urine samples from rats were collected to detect urinary protein content. The kidney was isolated and the ratio of kidney weight/body weight (index of kidney weight) was detected. The levels of fasting blood glucose, glycosylated hemoglobin serum urea nitrogen and serum creatinine were measured. Morphological changes of renal tissue were observed by optical microscope. The protein expressions of ALDH2 and JNK in renal tissue were detected by Western blot.</p><p><b>RESULTS</b>Compared with the normal control rats, the levels of fasting blood glucose, glycosylated hemoglobin, serum urea nitrogen, serum creatinine and the index of kidney weight were increased markedly in diabetic rats. The expression of ALDH2 protein was decreased, while p-JNK, JNK protein expressions and the ratio of p-JNK/JNK were increased. The morphological observation was shown that the amount of glomerular mesangial matrix were increased, basement membrane were thickened and capillary lumen were narrowed. However,in ethanol + diabetes group, renal function was improved and the damage of renal structure was attenuated. The expression of ALDH2 protein was increased, while p-JNK, JNK and the ratio of p-JNK/JNK were decreased.</p><p><b>CONCLUSION</b>Enhanced ALDH2 expression can protect kidney in diabetic rats, which may be relevant with inhibitting the activity of JNK pathway.</p>

Effect of ALDH2 activation against myocardial ischemia/reperfusion injury in diabetic rat / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To observe the role of activation of aldehyde dehydrogenase 2 (ALDH2) on myocardial ischemia/reperfusion (I/ R) injury in diabetic rats.</p><p><b>METHODS</b>Diabetic rat model was simulated by intraperitoneal injection 55 mg/kg streptozotocin (STZ) and divided into diabetes and ethanol + diabetes groups (n = 8). After 8 weeks, myocardial ischemia/reperfusion model was mimicked in vitro. The ventricular dynamical parameters and lactate dehydrogenase (LDH) content in coronary flow were determined. The fasting blood glucose and glycosylated hemoglobin (HbA1c) level were determined by automatic biochemistry analyzer. The ALDH2 mRNA and protein expressions of left anterior myocardium were evaluated by RT-PCR and Western blot.</p><p><b>RESULTS</b>In contrast to I/R in normal rat, in diabetic rat, left ventricular development pressure (LVDP), maximal rise/fall rate of left ventricular pressure (+/- dp/dtmax) and left ventricular work (RPP) were decreased, left ventricular end diastolic pressure (LVEDP) and LDH release were increased, and ALDH2 mRNA and protein expressions were decreased; compared with I/R in diabetic rat, ALDH2 agonist ethanol significantly promoted the recovery of LVDP, +/- dp/dtmax, RPP, reduced HbA1c level, LVEDP and LDH released, ALDH2 mRNA and protein expressions were increased.</p><p><b>CONCLUSION</b>In diabetic rat, the expression of ALDH2 was decreased when heart was subjected to I/R. Enhanced mitochondrial ALDH2 expression in diabetic rat could play cardiac protective role.</p>

Anti-apoptotic role of mitochondrial aldehyde dehydrogenase 2 in myocardial ischemia/reperfusion injury in diabetic rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the anti-apoptotic effect of aldehyde dehydrogenase 2 (ALDH2) on myocardial ischemia/reperfusion (I/R) injury in diabetic rats.</p><p><b>METHODS</b>Normal male SD rats were divided into normal, diabetes and ethanol (the agonist of ALDH2) + diabetes groups. In the latter two groups, diabetes was induced by an intraperitoneal injection of 55 mg/kg STZ. Four weeks after the modeling, myocardial I/R was mimicked ex vivo, and lactate dehydrogenase (LDH) content in the coronary flow was determined. The activities of caspase-3 and ALDH2 were evaluated, and the expressions of Bcl-2 and Bax mRNA in the left anterior myocardium were detected using RT-PCR.</p><p><b>RESULTS</b>In diabetic group, LDH release and caspase-3 activity were increased, while ALDH2 activity and Bcl-2/Bax mRNA expression were decreased as compared to those in normal control group. Compared with the diabetic group, ALDH2 agonist ethanol significantly reduced LDH release and caspase-3 activity, increased ALDH2 activity and Bcl-2/Bax mRNA expression.</p><p><b>CONCLUSION</b>In diabetic rats, enhanced ALDH2 expression can offer mycardial protection possibly in relation to suppress cell apoptosis.</p>