Cardioprotective Effects of Qishen Granule(芪参颗粒)on Sarcoplasmic Reticulum Ca^2＋ Handling in Heart Failure Rats

Objective：To assess the effects of Qishen Granule（芪参颗粒, QSG） on sarcoplasmic reticulum（SR） Ca^2＋ handling in heart failure（HF） model of rats and to explore the underlying molecular mechanisms. Methods：HF rat models were induced by left anterior descending coronary artery ligation surgery and high-fat diet feeding. Rats were randomly divided into sham（n=10）, model（n=10）, QSG（n=12, 2.2 g/kg daily） and metoprolol groups（n=12, 10.5 mg/kg daily）. The therapeutic effects of QSG were evaluated by echocardiography and blood lipid testing. Intracellular Ca^2＋ concentration and sarco-endoplasmic reticulum ATPase 2a（SERCA2a） activity were detected by specific assay kits. Expressions of the critical regulators in SR Ca^2＋ handling were evaluated by Western blot and real-time quantitative polymerase chain reaction. Results：HF model of rats developed ventricular remodeling accompanied with calcium overload and defective Ca^2＋ releaseuptake cycling in cardiomyocytes. Treatment with QSG improved contractive function, attenuated ventricular remodeling and reduced the basal intracellular Ca^2＋ level. QSG prevented defective Ca^2＋ leak by attenuating hyperphosphorylation of ryanodine receptor 2, inhibiting expression of protein kinase A and up-regulating transcriptional expression of protein phosphatase 1. QSG also restored Ca^2＋ uptake by up-regulating expression and activity of SERCA2 a and promoting phosphorylation of phospholamban. Conclusion：QSG restored SR Ca^2＋cycling in HF rats and served as an ideal alternative drug for treating HF.

Effect of angiotensin converting enzyme inhibitor on the calcium transients and calcium handling proteins in ventricular myocytes from rats with heart failure

Background Chronic heart failure (CHF) is associated with calcium transients and calcium handling proteins. Angiotensin converting enzyme (ACE) inhibitor has been demonstrated to have beneficial effect on CHF. Yet studies addressed to the relationship between ACE inhibitor and calcium transients in CHF are rare. The aim of this study was to investigate the influence of ACE inhibitor (perindopril) on the contractility and calcium transients and calcium handling proteins in ventricular myocytes from rats with experimental heart failure.Methods Male Wistar rats were randomized to heart failure group treated with perindopril (CHF-T, 3 mg·kg -1 ·d -1 ), heart failure group without treatment (CHF-C) and sham-operated group (PS). Heart failure was induced by abdominal aortic constriction. All groups were further followed up for 12 weeks. Left ventricular myocytes were then isolated. Single cell shortening fraction and [Ca 2+ ]_i were simultaneously measured by laser scanning confocal microscope under the field stimulation (1.0 Hz). Reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot were performed to evaluate the changes of mRNA and protein of Na +-Ca 2+ exchanger (NCX_1), sarcoplasmic reticulum Ca 2+ -ATPase (SERCA_2) and phospholamban (PLB).Results The fraction of cell shortening (FS%) and [Ca 2+ ]_ imax (nmol/L) were significantly reduced in group CHF-C compared with group PS (FS%: 7.51±1.15 vs 13.21±1.49;[Ca 2+ ]_ imax :330.85±50.05 vs 498.16±14.07; both P <0.01), and restored at least partially in CHF-T group. In CHF-C group, the left ventricular mRNA of NCX_1 and PLB were significantly upregulated in comparing with PS group (R_ NCX1/β-Actin : 0.51±0.12 vs 0.19±0.06, P <0.01; R_ PLB/β-Actin : 0.26±0.12 vs 0.20±0.08, P <0.05), while SERCA_2 mRNA was downregulated (0.48±0.10 vs 0.80±0.11, P <0.01). The mRNA levels of NCX_1 and SERCA_2 in CHF-T group were between the CHF-C and PS group, and the differences of the latter two groups were significant (all P <0.05). In CHF-C and CHF-T groups, the protein expression of NCX_1 were 1.141±0.047 and 1.074±0.081 times of that in PS group respectively (both P <0.05), and SERCA_2 protein levels were 0.803±0.100 and 0.893±0.084 times of that in PS group respectively (both P <0.05). The protein expression of NCX_1 and SERCA_2 in the CHF-C and CHF-T groups is significantly different (both P <0.05).ConclusionACE inhibitor could improve cardiac function of failing heart through directly enhancing the contractility of single cardiomyocyte, and these effects are probably mediated by its roles in preventing the deleterious changes of calcium transients and calcium handling proteins in CHF.

An Aggregation Composition Compensation Method Based on Paired Net

With regard to the failure and cancellation of business logic of web services composition(WSC),this paper propose a novel web services transaction compensation mechanism based on paired net which can dynamically establish agile compensation-triggered process(CSCP-Nets),and satisfy prospective compensation requirements.The related execution semantics of five usual composition compensation patterns based on paired net are analyzed in the situations of successful execution,failure compensation and failure recovery.Paired net based application of trip reservation process(TRP) shows that it is feasible.