Effect of calcium-sensing receptor in cardiac hypertrophy induced by angiotensin Ⅱ in cultured neonatal rat cardiomyocytes / 中国地方病学杂志

Objective To explore the roles and possible mechanism of calcium-sensing receptor(CaSR) in cell cardiac hypertrophy model using angiotensin Ⅱ (Ang Ⅱ ).Methods The cultured neonatal rat ventricular myocytes were treated with Ang Ⅱ as cell cardiac hypertrophy model.Hypertrophic neonatal rat cardiomyocytes were treated with GdCl3(a specific agonist of CaSR) and/or with Ro318220(a specific inhibitor of PKC pathway).To evaluate the status of cardiac hypertrophy,cell diameter was observed by HE dyeing,and protein content was determined through coomassie brilliant blue protein kit.The intracellular calcium concentration( [ Ca2+]i) was determined by laser scanning confocal microscope.The protein expression of CaSR and PKC pathway were analyzed using Western blotting.Results ①Compared to the control group(0.1263 ± 0.0443),the protein expression of CaSR was increased in Ang Ⅱ group and in GdCl3 group(0.1963 ± 0.0375,0.2778 ± 0.0564,all P＜ 0.05).Moreover,compared with Ang Ⅱ alone,the increase was significant in GdCl3 group(P ＜ 0.05).②Compared to control group(222.70 ± 22.09),AngⅡ group(392.16 ± 36.85) remarkably increased [Ca2+]i(P＜ 0.05),and this increase of [Ca2+]i was further enhanced in GdCl3 group (502.60 ± 44.21) versus Ang Ⅱ group (P ＜ 0.05).③Compared to control group,Ang Ⅱ could induce cardiomyocyte hypertrophy,and GdCl3 enhanced the effect.Moreover,this enhancement was attenuated by Ro318220.④Compared to control group(0.27 ± 0.07,0.69 ± 0.06,0.87 ± 0.04),the protein expression of PKCα,PKCε and PKCδ was increased in Ang Ⅱ group(0.60 ± 0.16,1.02 ± 0.13,1.20 ± 0.18,all P＜ 0.05) and the protein expression of PKCα,PKCε was increased in GdCl3 group(0.82 ± 0.16,1.34 ± 0.12,all P ＜ 0.05).Moreover,compared with Ang Ⅱ group,the protein expression of PKCα,PKCε was obviously increased in GdCl3 group (all P ＜ 0.05);compared with GdCl3 group,the protein expression of PKCα,PKCε(0.41 ± 0.10,0.85 ± 0.14) was obviously decreased in Ro318220 group(all P ＜ 0.05).Conclusions CaSR is involved in cardiac hypertrophy induced by Ang Ⅱ through PKC pathway in cultured neonatal rat cardiomyocytes.

Effect of artemisinin on ischemia/reperfusion injury of isolated rat myocardium / 中国中药杂志

<p><b>OBJECTIVE</b>To observe the effect of artemisinin on the ischemia/reperfusion injury of the iisolated rat myocardium and to preliminarily study the possible mechanism.</p><p><b>METHOD</b>Fifty Wistar rats were randomly divided into 5 groups: a control group, an ischemia/reperfusion (I/R) group, and 3 artemisinin (AS) groups (10, 100, 1000 micromol x L(-1)), 10 rats in each group. Ischemia/reperfusion injury of the isolated rat myocardium was induced by a Langendorff system. The electrocardiogram, the cardiac functional parameters, coronary flow, and the activities of LDH (lactate dehydrogenase), CPK (creatine phosphokinase), SOD (superoxide dis-mutase) and the level of malondiadehyde (MDA) in myocardial tissue, and the myocardial ultrastructures were investigated.</p><p><b>RESULT</b>AS (10,100 micromol x L(-1)) could significantly improve the index of the myocardial function (+/- dp/dt(max), LVSP) after the ischemia/reperfusion, increase the coronary flow, decrease the leakage of LDH and CPK, and increase the SOD activity and decrease the MDA level in cardiac tissues, and alleviate the myocardial ultrastructure injury. But, AS (1000 micromo x L(-1)) did not have the above effects.</p><p><b>CONCLUSION</b>AS (10, 100 micromol x L(-1)) alleviate the myocardial ischemia/reperfusion injury in rats. The mechanism may be related to its functions of antioxidation and scavenging free radicals.</p>

Protective effect of quercetin against adriamycin-induced cardiotoxicity and its mechanism in mice / 药学学报

This study is to investigate the protective effect of quercetin against adriamycin-induced cardiotoxicity and its mechanism. The cardiotoxicity was induced by intraperitoneal injection of adriamycin (ADR) at a single dose of 20 mg x kg(-1). Mice were randomly divided into 5 groups (n=20): normal control group, ADR 20 mg x kg(-1) group, quercetin (50, 100, and 200 mg x kg(-1) groups, intragastric administration, once a day, for 7 days before ADR administration). The health conditions, electrocardiogram, activity of iNOS, SOD and LDH, levels of NO and MDA in serum or tissue homogenate, the ultrastructure and the expression of p53 protein in cardiac tissue of mice were observed. Compared with the normal control group, ADR decreased the amplitude of ECG's R wave (P < 0.001), increased the incidence of arrhythmia (to 60%), injured myocardial ultrastructure, increased the activity of LDH and iNOS, and levels of NO and MDA, decreased the activity of SOD, and increased the expression of p53 (P < 0.001). Compared with ADR 20 mg x kg(-1) group, the quercetin decreased the levels of LDH, iNOS, NO and MDA, increased the activity of SOD, restored the amplitude of R wave, decreased the incidence of arrhythmia and p53 expression (P < 0.001 , P < 0.01 or P < 0.05), and markedly reduced the myocardial ultrastructure injury. Quercetin had protective effect against adriamycin-induced cardiotoxicity. The mechanism may be related to its enhancing myocardial SOD activity, decreasing iNOS activity and inhibiting myocardial apoptosis.