RESUMEN
1. It has been well established that oestrogens can increase the number of endothelial progenitor cells (EPC) by anti-apoptotic effects. Resveratrol, a polyphenolic phytoalexin extracted from grapes and wine, has been reported to act as an oestrogen receptor agonist. We hypothesize that putative phyto-oestrogen may promote EPC proliferation and survival in vitro. 2. Endothelial progenitor cells were isolated from human peripheral blood and identified immunocytochemically. Endothelial progenitor cells were incubated with resveratrol (1, 10, 25 and 50 mmol/L) or control for specified times. Cell proliferation, migration and in vitro vasculogenesis were assayed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetra-zolium bromide (MTT) assay, modified Boyden chamber assay and in vitro vasculogenesis detection, respectively. 3. Resveratrol increased the number of EPC and promoted EPC proliferation, adhesion and migration in a dose- and time-dependent manner. Cell number peaked at 50 mmol/L resveratrol after incubation for 24 h compared with vehicle control (61.3 +/- 5.8 vs 112.8 +/- 7.2, respectively; P < 0.01). 4. Furthermore, cell cycle analysis showed that 50 mmol/L resveratrol significantly increased the S phase and decreased the G(0)/G(1) phase of EPC. In addition, resveratrol increased vascular endothelial growth factor production and further induced vasculogenesis in vitro. 5. In conclusion, resveratrol significantly induces EPC proliferation, migration and further promotes angiogenesis in vitro.
Asunto(s)
Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Endoteliales/efectos de los fármacos , Neovascularización Fisiológica/efectos de los fármacos , Fitoestrógenos/farmacología , Células Madre/efectos de los fármacos , Estilbenos/farmacología , Adhesión Celular/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Relación Dosis-Respuesta a Droga , Células Endoteliales/metabolismo , Fase G1/efectos de los fármacos , Humanos , Fase de Descanso del Ciclo Celular/efectos de los fármacos , Resveratrol , Fase S/efectos de los fármacos , Células Madre/metabolismo , Factores de Tiempo , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
OBJECTIVE: To assay the expression of KiSS-1 and GnRH in the male rat hypothalamus at different developmental stages, and to explore the significance of KiSS-1 in sex development onset and normal reproduction regulation. METHODS: Expression analyses of KiSS-1 and GnRH genes were conducted in the rat hypothalamus at different developmental stages with RT-PCR and real time-PCR. The testosterone level was assayed by chemoluminescence technique. RESULTS: KiSS-1 mRNA rose gradually during sex development in the rat hypothalamus, highest at puberty and lowered a little at adulthood. KiSS-1 mRNA of the prepubertal, early pubertal, pubertal and adult rats was 1.7, 2.1, 3.5 and 2.0 times higher than that of the infantile rats respectively. The expression of GnRH and KiSS-1 correlated positively (r = 0.905, P < 0.05). But the activation of GnRH neuron was later than KiSS-1. The expression of GnRH was the highest in the puberty rats. GnRH mRNA of the prepubertal, early pubertal, pubertal and adult rats was 1.1, 1.94, 2.42 and 1.92 times higher than that of the infantile rats respectively. The level of testosterone in the adult rats was significantly higher than that at the earlier stage and was the highest at the adult stage. CONCLUSION: The expression of KiSS-1 correlates positively with that of GnRH. KiSS-1 may participate in the regulation of GnRH and is relevant to puberty onset and the regulation of reproduction function.