RESUMO
The aim of this study was to investigate the role of the rat neuregulin-1 (NRG-1) protein in reducing doxorubicin (DOX)-induced myocardial toxicity and its underlying mechanism. The prokaryotic expression of the NRG-1 protein and the CCK8-determined activity of rat primary myocardial cells were evaluated under different DOX concentrations. Myocardial cells were divided into three groups: the control group, the 5 µM DOX (DOX5) group, and the DOX5+NRG-1 group. Western blotting was used to determine the Na+-Ca2+ exchanger (NCX-1) and cardiac myosin light-chain kinase (cMLCK) protein expression levels and real-time quantitative polymerase chain reaction methods were used to determine the mRNA expression levels. The prokaryotic expression of NRG-1 in the DOX5 group produced toxicity in the rat myocardial cells, and cell activity was significantly restored with the addition of NRG-1. The protective effect of NRG-1 was limited at higher DOX concentrations (DOX10), and the degree of cellular activity restoration was positively correlated with NRG-1 concentration. The addition of NRG-1 to DOX5 intervention inhibited NCX-1 protein and mRNA expression, and increased cMLCK protein and mRNA expression. In conclusion, DOX-induced toxicity in rat myocardial cells could be protected by NRG-1, and the mechanism may be related to the role of NRG-1 in up-regulating the cMLCK expression level and down-regulating the NCX-1 expression level.
Assuntos
Cardiomiopatias/metabolismo , Doxorrubicina/efeitos adversos , Miócitos Cardíacos/efeitos dos fármacos , Neuregulina-1/metabolismo , Substâncias Protetoras/metabolismo , Animais , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/patologia , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Doxorrubicina/administração & dosagem , Regulação da Expressão Gênica/efeitos dos fármacos , Ratos , Ratos Sprague-DawleyRESUMO
The objective of the study was to determine the long-term effects of melatonin treatment on cashmere production and hair follicle populations in cashmere goats and their activity in two consecutive cashmere growth cycles. Twenty-four female Inner Mongolian Cashmere goats were randomly allocated to two groups (n = 12), one of which received melatonin implants, the other being an untreated control group. Melatonin implants were subcutaneously inserted behind the ear at a dose of 2 mg/kg live weight on two occasions -April 30 and June 30, 2016. Hair samples were collected by combing in April of 2017 and 2018, and the weight, staple length, and diameter of the cashmere fibers were measured. Blood and skin samples were collected monthly between April and September 2016, and in April and September in 2017 for the analysis of melatonin concentration and the characteristics of secondary hair follicle populations, respectively. The results indicated that serum melatonin concentration in the treated goats was elevated (P < 0.05) relative to that of the control group, but only during the first growth cycle. Melatonin treatment of cashmere goats in one cashmere growth cycle increased the weight, staple length, and density (all P < 0.05) of the cashmere fibers and decreased fiber diameter (P < 0.01), but did not affect the characteristics of cashmere production in the subsequent annual cycle. Melatonin treatment had no effect on the population of skin secondary hair follicles for two consecutive cycles. However, in the first growth cycle after treatment, it advanced the onset of activity of skin secondary hair follicles by 2 mo (P < 0.05), and it increased the number of follicles that were active (P < 0.05). In summary, the melatonin treatment of cashmere goats in one cashmere growth cycle improved cashmere production for that cycle only, with no residual effects on the subsequent cycle, a technique acceptable to the cashmere goat industry. The enhancement of cashmere production after the treatment of goats with melatonin appears to involve the acceleration of the annual regeneration of skin secondary hair follicles and increased population of active secondary hair follicles in the skin of cashmere goats.
Assuntos
Antioxidantes/farmacologia , Cabras/fisiologia , Folículo Piloso/efeitos dos fármacos , Melatonina/farmacologia , Animais , Antioxidantes/administração & dosagem , Implantes de Medicamento , Feminino , Cabelo , Folículo Piloso/crescimento & desenvolvimentoRESUMO
This study was conducted to investigate effects of short-term nutritional supplementation on concentrations of reproductive hormones in follicular fluid and on mRNA abundance in granulosa cells (GCs) during the luteal phase of ewes. Eighteen ewes were randomly assigned to treatment or control groups (n = 9, each group). All the ewes were subjected to estrous synchronization using a Controlled Intravaginal Releasing Device (CIDR). From the second to the eleventh day of estrous synchronization, ewes were fed a diet with a relatively greater (treatment group) or a maintenance (control group) energy content. Samples of follicular fluid and GCs were collected from antral follicles of estrous ewes after CIDR removal. The results indicate mean FSH concentration of fluid in small follicles and mean LH concentrations of fluid in large follicles of the ewes in the treatment group were greater (P < 0.05) than that of ewes in the control group. Follicular fluid E2 concentrations were directly related (P < 0.05) to follicular diameter. The ewes of the treatment group had greater (P < 0.05), compared with the control group, abundances of Follicle Stimulating Hormone Receptor (FSHR) in small and medium follicles, and (P<0.05) Luteinizing Hormone Receptor (LHR), Steroid Acute Regulatory Protein (STAR), cytochrome P450 (CYP17A1, CYP19A1) enzyme and Estrogen Receptor (ESR1) in large follicles. The results of this study provide evidence for a potential mechanism by which short-term nutritional supplementation improves follicular development possibly because of increased expression of steroid synthesis-regulating genes in large follicles.
Assuntos
Suplementos Nutricionais , Ingestão de Energia , Líquido Folicular/química , Células da Granulosa/metabolismo , RNA Mensageiro/metabolismo , Ovinos/fisiologia , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Dieta/veterinária , Sincronização do Estro , Feminino , Hormônio Foliculoestimulante/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Folículo Ovariano/metabolismoRESUMO
Coronary artery disease (CAD) receives intensive attentions in the research of cardiovascular diseases, due to its high incidence and severe impact on the quality of life vascular endothelial growth factor (VEGF), a potent angiogenic and vascular permeability factor, has been strongly implicated in the pathogenesis of CAD. Genetic markers in different regions of the VEGF gene have a plausible role in modulating the risk of CAD. To identify the markers contributing to the genetic susceptibility to CAD, we examined the potential association between CAD and 10 single nucleotide polymorphisms (SNPs, rs699947, rs1570360, rs2010963, rs833068, rs3024997, rs3025000, rs3025010, rs3025020, rs3025030, rs3025039) of the VEGF gene using the MassARRAY system. Participants included 242 CAD patients and 253 healthy controls from a Chinese Han Population (He'nan Province, China). The allelic or genotypic frequencies of the rs699947 (5' untranslated regions, 5'UTR) and rs2010963 (5'UTR) polymorphisms in the CAD patients were significantly different from those in the healthy controls. The CAD patients had significantly higher frequency of the rs699947 A allele (χ(2)=11.141, P=0.001, OR=1.665, 95% CI=1.232-2.250) and rs2010963 C allele (χ(2)=13.593, P=0.0002, OR=1.611, 95% CI=1.249-2.077). Strong linkage disequilibrium was observed in the rs699947-rs1570360-rs2010963 haplotype block (D'>0.9). Significantly more C-G-C haplotypes (P=0.040) and significantly fewer C-G-G haplotypes (P=0.0004) were found in the CAD patients. The possible association of rs699947 and rs2010963 with CAD risks warrant confirmation in independent case-control studies and may be informative for future investigations on the pathogenesis of CAD.