鸢尾苷元对血管紧张素Ⅱ作用下心肌成纤维细胞增殖和凋亡的影响

目的探讨鸢尾苷元对血管紧张素Ⅱ(AngⅡ)作用下心肌成纤维细胞增殖和凋亡的影响及其机制。方法采用差速贴壁法获得纯化的大鼠心肌成纤维细胞,采用MTT法和原位末端标记法检测鸢尾苷元或磷脂肌醇-3-激酶(PI3K)/蛋白激酶B(Akt)信号通路对AngⅡ作用下心肌成纤维细胞增殖和凋亡的影响,采用RT-PCR检测鸢尾苷元对AngⅡ作用下心肌成纤维细胞中凋亡相关基因Bcl-2、Bax mRNA表达的影响,Western blot法检测鸢尾苷元对AngⅡ作用下心肌成纤维细胞中凋亡相关蛋白Bcl-2、Bax和PI3K/Akt信号通路相关蛋白p-Akt、T-Akt表达的影响。结果 AngⅡ能明显促进心肌成纤维细胞增殖,抑制细胞凋亡;给予50,100和200μmol·L^-1鸢尾苷元后,AngⅡ使心肌成纤维细胞促增殖和抑凋亡作用明显受到抑制,且200μmol·L^-1鸢尾苷元作用最显著。200μmol·L^-1鸢尾苷元能够明显抑制AngⅡ诱导的Bcl-2 mRNA和p-Akt、Bcl-2蛋白的表达;减弱AngⅡ对Bcl-2 mRNA和蛋白表达的...     

表食子儿茶素没食子酸酯对皮质酮损伤神经细胞的保护效应及其作用机制

目的：研究表没食子儿茶素没食子酸酯（EGCG）对皮质酮损伤神经细胞的作用及对细胞内PI3K/Akt信号的影响。方法：用MTT法检测细胞损伤程度,构建皮质酮（CORT）应激损伤细胞模型;倒置显微镜下观察细胞形态变化;Hochest染色观察细胞凋亡情况;免疫印迹方法检测细胞p-Akt、Akt蛋白表达变化。结果：与正常对照组相比,模型组细胞存活率明显降低,细胞形态改变,突触收缩,凋亡增加,Akt磷酸化降低;当给予EGCG后,细胞存活率提高,细胞形态有所恢复,细胞凋亡减少,Akt磷酸化水平升高;先给予PI3K/Akt阻断剂后,EGCG对细胞存活率的升高作用和对细胞形态的缓解作用均被抑制。结论：EGCG能缓解CORT对PC12细胞的损伤作用,而PI3K/Akt信号在EGCG神经保护效应中具有重要作用。     

萝卜硫素通过Src/PI3K/Akt通路调控人脐静脉内皮细胞NO的生成机制

目的:研究萝卜硫素(SFN)促进人脐静脉内皮细胞(human umbilical vein endothelial cells,HUVEC)生成一氧化氮(NO),参与内皮细胞修复的作用机制.方法:采用MTT法检测SFN对HUVEC细胞存活率的影响;检测SFN对HUVEC NO释放量的影响;采用Western blot法...     

Akt介导VEGF信号通路在促进胃癌淋巴管新生中的作用

随着研究的深入,肿瘤淋巴管新生已被证实在实体肿瘤淋巴转移途径中起着至关重要的作用,并可作为一个评价肿瘤预后的重要指标.但长期以来由于缺乏对淋巴管内皮特异因子和淋巴管检测技术的认识,对淋巴管转移具体机制与肿瘤淋巴管新生分子途径尚未完全明确.Akt信号通路是细胞内一条重要的信号传导通路,与肿瘤发生、增殖、抗凋亡、转移等密切相关.近年来发现Akt在介导VEGF信号通路与肿瘤淋巴管转移或肿瘤淋巴管新生的也存在着密切关系.本文对Akt信号通路在胃癌淋巴管新生中重要作用与研究进展作一综述.     

Mussel oligopeptides ameliorate cognition deficit and attenuate brain senescence in d-galactose-induced aging mice

Dietary supplementation exerts beneficial effects in reducing incidence of chronic neurodegenerative diseases. The purpose of this study was to examine protective effects of mussel (Mytilus edulis) oligopeptides supplementation on brain function in d-galactose induced aging mice. Sixty female 8-month-old mice were randomly divided into five groups: vehicle control, d-galactose, and d-galactose combined with 200, 500, 1000 mg/kg mussel oligopeptides. The results showed that mussel oligopeptides could improve cognitive learning and memory ability and protect the hippocampal neurons. In addition, GSH, SOD and GSH-pX activities were increased and MDA level was significantly decreased in mice fed with mussel oligopeptides. It was also found that mussel oligopeptides supplementation prevented d-galactose-induced elevations of iNOS activity and NO production and lactate acid levels in brain. Moreover, PI3K and Akt genes were up-regulated by mussel oligopeptides supplementation. These findings suggest that mussel oligopeptides are able to enhance exercise capacity and protect against oxidative damage caused by d-galactose in aging model mice through regulating oxidation metabolism and PI3K/Akt/NOS signal pathway. Therefore, mussel oligopeptides are good materials for future development of healthcare products to combat age-related brain dysfunction and to improve healthy life span.     

妊娠期糖尿病孕妇胎盘组织Akt和GLUT-1的表达与新生儿体重的相关性

目的探讨妊娠期糖尿病(GDM)孕妇胎盘组织Akt和GLUT-1的表达与新生儿体重的相关性。方法选取我院收治的40例GDM患者作为研究组,另选取40例健康孕妇作为对照组,检测两组孕妇的孕期BMI、孕期增重、 FPG、 FINS、HbA1c水平,分析胎盘组织Akt和GLUT-1表达情况及其与新生儿体重的相关性。结果研究组胎盘组织Akt和GLUT-1表达明显低于对照组(P <0.05)。Pearson相关性分析显示,Akt表达(r=-0.697, P=0.035)、 GLUT-1表达(r=-0.768, P=0.029)均与新生儿体重呈负相关。结论 GDM孕妇胎盘组织中Akt和GLUT-1表达水平下降可能是造成新生儿体重上升的原因。     

The anti-fibrotic effects of epigallocatechin-3-gallate in bile duct-ligated cholestatic rats and human hepatic stellate LX-2 cells are mediated by the PI3K/Akt/Smad pathway

Aim:

(−)-Epigallocatechin-3-gallate (EGCG) is one of the most abundant polyphenols in green tea with strong antioxidant activity and various therapeutic effects. In this study, we investigated the anti-fibrotic effects of EGCG and underlying mechanisms in bile duct-ligated (BDL) rats and a liver fibrosis model in vitro.

Methods:

BDL rats were treated with EGCG (25 mg·kg⁻¹·d⁻¹, po) for 14 d, and then the serum, bile and liver samples were collected. Liver fibrosis was assessed by serum, urine and bile biochemistry analyses and morphological studies of liver tissues. TGF-β1-stimulated human hepatic stellate LX-2 cells were used as a liver fibrosis model in vitro. The expression of liver fibrogenic genes and signaling proteins in the PI3K/Akt/Smad pathway was examined using Western blotting and/or real-time PCR.

Results:

In BDL rats, EGCG treatment significantly ameliorates liver necrosis, inflammation and fibrosis, and suppressed expression of the genes associated with liver inflammation and fibrogenesis, including TNF-α, IL-1β, TGF-β1, MMP-9, α-SMA, and COL1A1. In LX-2 cells, application of EGCG (10, 25 μmol/L) dose-dependently suppressed TGF-β1-stimulated expression of COL1A1, MMP-2, MMP-9, TGF-β1, TIMP1, and α-SMA. Furthermore, EGCG significantly suppressed the phosphorylation of Smad2/3 and Akt in the livers of BDL rats and in TGF-β1-stimulated LX-2 cells. Application of {"type":"entrez-nucleotide","attrs":{"text":"LY294002","term_id":"1257998346","term_text":"LY294002"}}LY294002, a specific inhibitor of PI3K, produced similar effects as EGCG did in TGF-β1-stimulated LX-2 cells, but co-application of EGCG and {"type":"entrez-nucleotide","attrs":{"text":"LY294002","term_id":"1257998346","term_text":"LY294002"}}LY294002 did not produce additive effects.

Conclusion:

EGCG exerts anti-fibrotic effects in BDL rats and TGF-β1-stimulated LX-2 cells in vitro via inhibiting the PI3K/Akt/Smad pathway.     

Molecular mechanisms of human thyrocyte dysfunction induced by low concentrations of polychlorinated biphenyl 118 through the Akt/FoxO3a/NIS pathway

Polychlorinated biphenyls (PCBs) are typical persistent organic pollutants that can interfere with multiple organ systems of humans. Previously, we concluded that persistent exposure to low doses of PCB118 could severely damage the thyroidal structure, dramatically decrease the concentration of serum thyroid hormones and inhibit the pivotal gene expressions such as sodium/iodide symporter (NIS) and thyroglobulin (Tg). To explore the molecular mechanisms of thyrocyte dysfunction induced by 2,3′,4,4′,5‐pentachlorobiphenyl (PCB118), monolayer cultured human thyroid epithelial cells (HTECs) were treated with PCB118 or dimethyl sulfoxide (DMSO) as a control. Our results indicated that relatively higher concentrations of PCB118 could induce a loss in the viability of HTEC. In cultures with concentrations of PCB118 from 0.025 to 25 nM, which did not affect cell viability or apoptosis, concentrations of Tg and thyroxine (T₄) were significantly decreased compared with those in the controls. In addition, mRNA and protein levels of Akt were increased significantly in the PCB118‐treated groups, whereas FoxO3a expression did not show particular variation. Furthermore, exposure to PCB118 was associated with a significant increase of the protein levels of p‐Akt and p‐FoxO3a, and these effects were blocked by LY294002. In contrast, mRNA and protein expression levels of NIS were decreased significantly, and this effect was blocked by LY294002. Unlike control cells, a cytoplasmic shift of FoxO3a was observed in the PCB118‐treated group. Our research suggests that PCB118 may induce thyrocyte dysfunction through the Akt/FoxO3a/NIS signalling pathway, which provides potential new insights for finding interventions to counteract the damage to the human body caused by PCBs. Copyright © 2015 John Wiley & Sons, Ltd.