ABSTRACT
@#The purpose of this research is to investigate the therapeutic effects of losartan potassium on 5/6 nephrectomy rats with chronic heart failure(CHF)and to explore the mechanism. 24 Rats were randomly divided into three groups namely sham group(Sham), pathology group(Nx)and losartan potassium group(Lst), respectively. CHF model in rats were induced by 5/6 nephrectomy. At the 7th week, rats of Lst group were given losartan potassium(50 mg/L)for consecutive 2 weeks. Then all rats were measured for hemodynamic parameters, cardiac index, creatinine, urea nitrogen in serum, and expressions of CD133, VEGFR2, Sox2, cleaved Caspase-3 and Bcl-2 in heart. Compared with Nx group, rats of Lst group improved cardiac and renal functions: decreased LVDP, LVEDP, cardiac index, creatinine, urea nitrogen and increased LVSP. Furthermore, losartan potassium up-regulated gene expression of CD133, VEGFR2, Sox2 and protein level of Bcl-2, and down-regulated cleaved Caspase-3 protein expression. Results suggest that losartan potassium can improve cardiac function of rats with CHF which may be correlated with mobilizing bone marrow stem cells, increasing endothelial progenitor cells(EPCs)level in heart, repairing endothelial function, and inhibiting myocardial apoptosis.
ABSTRACT
OBJECTIVE:To study the influence of calcineurin gene polymorphism on the efficacy of cyclosporine A (CsA). METHODS:The blood samples of patients treated with CsA were collected. The trough blood concentration of CsA was detected by EMIT. The genotype of PPP3CA and PPP3CB was assayed by RFLP-PCR method. The expression of NFAT-regulated gene IL-2, IFN-γand GM-CSF were measured by RT-qPCR,which were used to define the index of indirect efficacy of CsA. The relationship of gene polymorphism with CsA efficacy was study by relationship analysis and multiple factor regression method,etc. RESULTS:A to-tal of 100 blood samples were collected. There was no significant correlation between the expression of CsA efficacy-related NFAT-reg-ulated gene GM-CSF and trough concentration of CsA(rGM-CSF=-0.04,P=0.238);the expression of IL-2 and IFN-γ were negatively correlated with trough concentration of CsA significantly(rIL-2=-0.384 3,P0.05). Stratified analysis showed that among patients with immune disease underwent renal transplantation,efficacy of patients with PPP3CB rs3763679 genovariation(TC+TT) were better than those with wild-type gene (CC)(P<0.05). After the efficacy was normalized by CsA trough concentration, multivariate analysis showed that normalized efficacy of CsA was negatively correlated with gender,PPP3CB rs3763679,lactate dehy-drogenase and creatinine significantly,but positively correlated with PPP3CA rs3804358,leucocyte count,usea nitrogen,glycerin trilaurate,etc. CONCLUSIONS:PPP3CB rs3763679 gene polymorphism influence the efficacy of CsA;among patients with immune disease underwent renal transplantation,efficacy of patients with PPP3CB rs3763679 TT+TC is better than that of CC type. At the same time,gender,PPP3CA rs3804358,leucocyte count,usea nitrogen,glycerin trilaurate and other factors all can influence the nor-malized efficacy of CsA to different extent. Multiple factors should be considered when using CsA.