Grape seed proanthocyanidin extracts prevent hyperglycemia-induced monocyte adhesion to aortic endothelial cells and ameliorates vascular inflammation in high-carbohydrate/high-fat diet and streptozotocin-induced diabetic rats

The role of grape seed proanthocyanidin extracts (GSPE) in the prevention of diabetic vascular inflammation and monocyte-endothelial cell interactions has not been examined. We used high-carbohydrate/high-fat diet and streptozotocin to induce diabetes and treated with GSPE (125, 250 and 500?mg/kg) for 24 weeks. Inflammatory response and intima-media thickness (IMT) in aortic root were observed by hematoxylin-eosin (H&;E) staining. The receptor of advanced glycation end products (RAGE) expression of aortic root was assayed by immunohistochemistry. Isolation of rat aortic endothelial cell (RAEC) was used to ex vivo monocyte adhesion assay. In this study, inflammatory response and IMT were significantly increased in diabetic rats compared to non-diabetic rats, which can be reversed by GSPE (p?p?相似文献   

邻苯二甲酸二异丁酯对小鼠海马cAMP/PKA-CREB信号转导通路的影响

目的观察邻苯二甲酸二异丁酯(DiBP)对小鼠海马cAMP/PKA-CREB信号通路的影响。方法 30只雄性昆明小鼠适应性喂养3天后,按体重随机分为一个对照组和4个实验组(Ⅰ、Ⅱ、Ⅲ、Ⅳ)。对照组小鼠灌胃给予玉米油溶剂;实验组小鼠灌胃给予含DiBP的玉米油溶液,剂量分别为:50、250、500、1000mg/kg BW。实验周期8周,普通饲料喂饲,自由饮水。实验结束后冰浴条件下取海马,采用酶联免疫法测定环磷酸腺苷(cAMP)含量;蛋白印迹法测定磷酸化蛋白激酶A(P-PKA C)、磷酸化环磷腺苷反应元件结合蛋白(P-CREB)表达水平;实时荧光定量PCR法测定CREB、脑源性神经营养因子(BDNF)、c-fos和c-jun的mRNA表达水平。结果第Ⅳ组海马组织中cAMP含量和P-PKA C蛋白表达水平明显低于对照组,差异具有统计学意义(P<0.05);各剂量组P-CREB蛋白表达量均低于对照组,其中第Ⅱ组与对照组相比差异有统计学意义(P<0.05),同时CREB、BDNF、c-fos和c-jun的mRNA表达水平与对照组相比都呈不同程度的下调。结论小鼠海马cAMP/PKA-CREB信号通路中多种信号分子的表达异常,可能是DiBP导致小鼠认知损伤的重要机制之一。     

茶色素抑制单核-内皮细胞粘附及其机制研究

为研究茶色素 (TP)对氧化型低密度脂蛋白 (Ox- L DL)损伤血管内皮细胞所致单核细胞粘附的影响 ,应用硫酸铜诱导低密度脂蛋白 (L DL )氧化 ,用细胞粘附实验、流式细胞仪荧光强度测定、细胞 EL ISA等方法分别从细胞、蛋白表达等方面研究茶色素对细胞间粘附分子 (ICAM- 1)和血管细胞间粘附分子 (VCAM-1)表达的影响。结果显示 ,80、40、2 0 mg/ L的 TP抑制 Ox- L DL诱导的单核细胞 -内皮细胞粘附 ,抑制 Ox-L DL 诱导的 ICAM- 1和 VCAM- 1表达并呈浓度依赖性。提示 TP抑制 ICAM- 1和 VCAM- 1的表达是其抑制单核细胞 -内皮细胞粘附及抗动脉粥样硬化的机制之一。     

Chocolate procyanidins decrease the leukotriene-prostacyclin ratio in humans and human aortic endothelial cells

BACKGROUND: Polyphenolic phytochemicals inhibit vascular and inflammatory processes that contribute to disease. These effects are hypothesized to result from polyphenol-mediated alterations in cellular eicosanoid synthesis. OBJECTIVE: The objective was to determine and compare the ability of cocoa procyanidins to alter eicosanoid synthesis in human subjects and cultured human aortic endothelial cells. DESIGN: After an overnight fast, 10 healthy subjects (4 men and 6 women) consumed 37 g low-procyanidin (0.09 mg/g) and high-procyanidin (4.0 mg/g) chocolate; the treatments were separated by 1 wk. The investigation had a randomized, blinded, crossover design. Plasma samples were collected before treatment and 2 and 6 h after treatment. Eicosanoids were quantitated by enzyme immunoassay. Endothelial cells were treated in vitro with procyanidins to determine whether the effects of procyanidin in vivo were associated with procyanidin-induced alterations in endothelial cell eicosanoid synthesis. RESULTS: Relative to the effects of the low-procyanidin chocolate, high-procyanidin chocolate induced increases in plasma prostacyclin (32%; P<0.05) and decreases in plasma leukotrienes (29%; P<0.04). After the in vitro procyanidin treatments, aortic endothelial cells synthesized twice as much 6-keto-prostaglandin F(1alpha) (P<0.01) and 16% less leukotriene (P<0.05) as did control cells. The in vitro and in vivo effects of procyanidins on plasma leukotriene-prostacyclin ratios in culture medium were also comparable: decreases of 58% and 52%, respectively. CONCLUSION: Data from this short-term investigation support the concept that certain food-derived flavonoids can favorably alter eicosanoid synthesis in humans, providing a plausible hypothesis for a mechanism by which they can decrease platelet activation in humans.     

人颈动脉斑块血管粘附蛋白1的表达及其与炎症的关系

目的研究血管粘附蛋白1(VAP-1)在人颈动脉斑块内的表达及其与炎性细胞的关系。方法采用免疫组化染色方法分析8例人颈动脉斑块内VAP-1、簇分化抗原4(CD4)和簇分化抗原68(CD68)表达情况。结果 VAP-1主要表达于颈动脉斑块内新生血管的内皮细胞,并与CD4和CD68阳性的炎性细胞成正相关。结论 VAP-1可能参与了炎性细胞通过新生血管侵入斑块的过程,未来可能成为标记或逆转易损斑块炎性反应的新靶点。     

Genistein inhibits insulin-like growth factor-I receptor signaling in HT-29 human colon cancer cells: a possible mechanism of the growth inhibitory effect of Genistein

Genistein, a soy isoflavone, has attracted much attention for its chemopreventive properties. Overexpression and constitutive activation of receptor tyrosine kinases are frequent events in human cancer. Because genistein has previously been reported to decrease HT-29 cell growth, the present study compared the effects of genistein with daidzein on the protein levels of the members of the ErbB receptor family and insulin-like growth factor-I (IGF-I) receptor (IGF-IR). HT-29 cells were cultured in serum-free medium, with 0, 25, 50, or 100 micromol/L genistein, daidzein, and/or 10 nmol/L IGF-I. DNA synthesis was estimated by 5-bromo-2'-deoxyuridine incorporation. Apoptotic cells were analyzed by annexin-V staining followed by flow cytometry. Genistein inhibited viable HT-29 cell numbers, in a dose-dependent manner, whereas daidzein had no effect on cell growth. The decrease in cell growth caused by genistein was due to decreased DNA synthesis and apoptosis induction. Immunoblot analysis showed that neither genistein nor daidzein decreased the protein levels of either of the epidermal growth factor receptors, ErbB2 or ErbB3. Genistein did, however, decrease the IGF-IR protein levels, whereas daidzein had no effect. Genistein did not change the protein levels of insulin-receptor substrate-1 (IRS-1), the p85 regulatory subunit of phosphatidylinositol 3-kinase (PI3K), or Akt. Immunoprecipitation/western blot analyses revealed that genistein decreased IGF-I-stimulated phosphorylation of IGF-IR and IRS-1, recruitment of p85 to IGF-IR, and phosphorylation of Akt. These results suggest that inhibition of cell proliferation and induction of apoptosis by genistein are mediated, at least in part, by its ability to inhibit IGF-IR signaling and the PI3K/Akt pathway.     

中国2型糖尿病药物治疗现状与血糖控制的调查研究

目的了解上海市普陀区社区管理2型糖尿病(T2DM)患者血糖及心血管疾病危险因素。方法采用系统抽样方法,抽取上海市普陀区10个社区在册管理的408例T2DM患者进行问卷调查、体格检查及实验室检测,收集人口学信息及血糖、血脂、血压控制情况并进行分析。结果共纳入408例T2DM患者,其中男性186例(45.59%),女性222例(54.41%),平均年龄为(66.86±6.97)岁。合并高血压者占61.27%,合并血脂异常者占60.05%,超重或肥胖者占56.62%。平均糖化血红蛋白(HbA1c)为(7.43±1.52)%。血糖(HbA1c < 7%)、血压(< 140/80 mmHg)、血脂达标(LDL-C < 2.6 mmol/L)的患者分别为48.77%、26.23%和26.72%,只有2.70%的患者HbA1c、血压、LDL-C同时达标。T2DM病程大于10年者,HbA1c达标率最低(P < 0.01)。多因素logistic回归分析显示,影响血糖达标的独立因素分别为吸烟、病程长、BMI高,影响血压达标的独立因素为睡眠时间≥7 h/d、超重/肥胖、腰臀比(WHR)高,影响血脂达标的独立因素为女性、腰围大。结论普陀区社区管理T2DM患者中,血糖、血压、血脂综合防治达标率不尽如人意,应加强对社区2型糖尿病患者心血管疾病危险因素的综合控制。     

Vitamin E increases production of vasodilator prostanoids in human aortic endothelial cells through opposing effects on cyclooxygenase-2 and phospholipase A2

Impairment of endothelium-dependent vasodilation is associated with the initiation and development of atherosclerosis. Vasodilator prostanoids constitute a protective mechanism in maintaining normal vasomotor function. In the current study, we determined the effect of in vitro vitamin E supplementation at physiologically relevant concentrations (10-60 micromol/L) on the production of the vasodilator prostanoids prostaglandin I(2) (PGI(2); prostacyclin) and prostaglandin E(2)(PGE(2)) by human aortic endothelial cells (HAECs) as well as its underlying mechanism. Results showed that vitamin E dose dependently (10-40 micromol/L) increased the production of both prostanoids by HAECs. This was associated with a dose-dependent (10-40 micromol/L) upregulation of cytosolic phospholipase A(2) (cPLA(2)) expression and arachidonic acid release. In contrast, vitamin E dose dependently (10-60 micromol/L) inhibited cyclooxygenase (COX) activity but did not affect the expression of either COX-1 or COX-2, indicating that the effect of vitamin E on COX activity was post-translational. Thus, vitamin E had opposing effects on the 2 key enzymes in prostanoid biosynthesis; at the concentrations used in this study, this resulted in a net increase in the production of vasodilator prostanoids. The vitamin E-induced increase in PGI(2) and PGE(2) production may contribute to its suggested beneficial effect in preserving endothelial function.     

Conjugated linoleic acids lower the release of eicosanoids and nitric oxide from human aortic endothelial cells

The objective of this study was to determine the effects of cis-9, trans-11 and trans-10, cis-12 CLA on the release of vasoactive eicosanoids and nitric oxide (NO) in human aortic endothelial cells. Experiments were conducted in which cells were incubated with these fatty acids, and the concentrations of various eicosanoids [6-keto prostaglandin (PG) F(1alpha) as a stable product of PGI(2), thromboxane (TX) B(2) as a stable product of TXA(2), and PGE(2)] and NO in the medium were determined. Cells treated with 50 micro mol/L of either cis-9, trans-11 or trans-10, cis-12 CLA released less of all of the eicosanoids and NO than control cells treated with medium alone (P < 0.05). The ratio between the amounts of 6-keto-PGF(1alpha) and that of TXB(2) released did not differ between control cells and cells treated with either CLA isomer. Moreover, cells treated with 50 micro mol/L of cis-9, trans-11 or trans-10, cis-12 CLA had a lower amount of arachidonic acid in their phosphatidylethanolamine fraction and a lower mRNA concentration and activity of secretory phospholipase A(2) than control cells (P < 0.05). These data suggest that eicosanoid formation was impaired by a reduced availability of arachidonic acid for the cyclooxygenase pathway. In conclusion, this study shows that cis-9, trans 11-CLA and trans-10, cis-12 CLA influence the release of various eicosanoids and NO from human aortic endothelial cells. The effects observed in this study might be important because eicosanoids and NO released from endothelial cells are involved in the regulation of vessel tone and platelet aggregation. The results of the present study suggest that both CLA isomers had unfavorable effects on endothelial function.     

光气染毒对小鼠肺Ⅱ型细胞凋亡及血管内皮生长因子的影响

目的　观察光气致肺水肿小鼠肺Ⅱ型细胞发生凋亡情况和血清、肺脏的血管内皮生长因子 (VEGF)、VEGF受体 (Flt1)的变化及肺脏VEGFmRNA的表达。方法　 2 6只二级BALB C小鼠 ,雄性 ,随机分为 2组 :对照组和染毒组 (各 13只 )。对照组小鼠以空气为对照 ,染毒组小鼠给予 11.9mg L剂量的光气 ,时间均为 5min ,染毒后 4h ,分离小鼠原代肺Ⅱ型细胞 ,电镜观察两组小鼠肺Ⅱ型细胞凋亡情况 ,酶联免疫法测定血清和肺脏的VEGF、Flt1的含量及反转录PCR法测定肺脏VEGFmRNA的表达。结果　电镜显示光气染毒肺水肿小鼠原代肺Ⅱ型细胞出现凋亡小体 ;染毒小鼠血清VEGF和肺脏的VEGF、Flt1含量 [(134.0 7± 12 0 .2 6 )、(4 77.76± 98.0 6 )、(12 818.4 8± 2 30 4 .15 )pg ml]明显低于对照组 [(4 4 5 .5 7± 173.30 )、(10 2 6 .87± 4 74 .5 6 )、(2 1976 .5 1± 74 2 1.0 1)pg ml],差异有显著性 (P <0 .0 5 ) ;染毒小鼠血清Flt1含量 [(2 36 9.5 6± 381.70 )pg ml]明显高于对照组 [(1898.0 0± 4 5 3.6 9)pg ml],差异有显著性 (P <0 .0 5 ) ;染毒小鼠肺脏VEGFmRNA表达降低。结论　光气经呼吸道染毒可引起肺水肿小鼠原代肺Ⅱ型细胞发生凋亡 ,使血清VEGF和肺脏VEGF、Flt1降低及肺脏VEGFmRNA表达降低。     

Purple sweet potato anthocyanins attenuate hepatic lipid accumulation through activating adenosine monophosphate–activated protein kinase in human HepG2 cells and obese mice

Purple sweet potato is a functional food rich in anthocyanins that possess disease-preventive properties. Anthocyanins are known to possess potent antidiabetic properties. However, the effect of the anthocyanin fraction (AF) from purple sweet potato on hepatic lipid metabolism remains unclear. Our hypothesis is that AF inhibits hepatic lipid accumulation through the activation of adenosine monophosphate–activated protein kinase (AMPK) signaling pathways in vitro and in vivo. In this study, we evaluated body weight, liver histology, and hepatic lipid content in high-fat diet (HFD)–fed ICR mice treated with AF. In addition, we characterized the underlying mechanism of AF's effects in HepG2 hepatocytes through Western blot analysis. Anthocyanin fraction (200 mg/kg per day) reduced weight gain and hepatic triglyceride accumulation and improved serum lipid parameters in mice fed an HFD for 4 weeks. Anthocyanin fraction significantly increased the phosphorylation of AMPK and acetyl-coenzyme A carboxylase (ACC) in the liver and HepG2 hepatocytes. In addition, AF down-regulated the levels of sterol regulatory element-binding protein 1 and its target genes including ACC and fatty acid synthase (FAS). The specific AMPK inhibitor compound C attenuated the effects of AF on the expression of lipid metabolism–related proteins such as SREBP-1 and FAS in HepG2 hepatocytes. The beneficial effects of AF on HFD-induced hepatic lipid accumulation are thus mediated through AMPK signaling pathways, suggesting a potential target for the prevention of obesity.     

Carnosic acid prevents the migration of human aortic smooth muscle cells by inhibiting the activation and expression of matrix metalloproteinase-9

The migration and matrix metalloproteinase (MMP) activation of vascular smooth muscle cells may play key roles in the development of atherosclerosis. Carnosic acid (CA) is a phenolic compound found in herbs, including rosemary and sage. Previous studies indicated that CA possesses antioxidant activity in vitro. In this study, we investigated the effects of CA on TNF-alpha-induced cell migration, the formation of intracellular reactive oxygen species, the translocation of NF-kappaB and the activation and expression of MMP-9 in human aortic smooth muscle cells (HASMC). The Matrigel migration assay showed that CA (10 and 20 micromol/l) effectively inhibited TNF-alpha-induced migration of HASMC as compared with the control group. To explain this inhibitory effect, MMP-9 was assayed by gelatin zymography and Western blot. The results indicated that CA inhibited MMP-9 activity and expression. Furthermore, the production of reactive oxygen species and the nuclear translocation of NF-kappaB p50 and p65 induced by TNF-alpha were dose-dependently suppressed by CA pretreament. These results indicate that CA has anti-inflammatory properties and may prevent the migration of HASMC by suppressing MMP-9 expression through down-regulation of NF-kappaB.     

血管内皮生长因子和Periostin检测在早期诊断糖尿病视网膜病变中的意义

目的 检测糖尿病视网膜病变(DR)患者血管内皮生长因子(VEGF)和Periostin表达的变化,并探讨其相关的临床意义.方法 选取发生DR的2型糖尿病患者52例(糖尿病DR组)、未发生DR的2型糖尿病患者36例(糖尿病非DR组)以及健康体检者30例(健康对照组),52例DR患者分为非增殖期组(24例)和增殖期组(28例).酶联免疫吸附法检测血清VEGF和Periostin的表达水平.结果 糖尿病非DR组和糖尿病DR组血清VEGF和Periostin表达均显著高于健康对照组[(122.63±28.74)、(163.58±42.37) mg/L比(91.53±19.58) mg/L,(110.15±32.62)、(146.51±41.74) mg/L比(82.26±21.17) mg/L,P＜0.05或＜0.01],并且糖尿病DR组血清VEGF和Periostin表达显著高于糖尿病非DR组(P＜0.05).增殖期组血清VEGF和Periostin表达显著高于非增殖期组[(174.15±47.31) mg/L比(147.66±38.25) mg/L,(160.31±46.43) mg/L比(132.14±35.62) mg/L,P＜0.05].VEGF表达与Periostin表达呈显著正相关(r=0.415,P＜ 0.01).结论 DR患者存在血清VEGF和Periostin高表达,二者的联合检测有利于DR的早期诊断以及病情的监控.     

Carbon ion irradiation suppresses metastatic potential of human non-small cell lung cancer A549 cells through the phosphatidylinositol-3-kinase/Akt signaling pathway

We previously showed that carbon ion irradiation can inhibit the expression of the anillin (ANLN) gene, which is regulated by the activation of the phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway associated with metastasis. The purpose of this study is to compare the effects of carbon ion irradiation on the PI3K/Akt signaling pathway to those of photon irradiation. Our study showed that carbon ion irradiation of human lung adenocarcinoma cells A549 decreased their invasion more effectively than photon irradiation did. We found that carbon ion irradiation reduced the nuclear localization of ANLN at lower dose, but did not affect its expression. Low-dose carbon ion irradiation also reduced the level of phosphorylated Akt compared to untreated controls, whereas photon irradiation did not. These results suggest that carbon ion irradiation effectively suppresses the metastatic potential of A549 cells by suppressing the PI3K/Akt signaling pathway.     

Turnover of acinar and islet cells in the pancreas of monosodium glutamate-treated obese mice

OBJECTIVE: Subcutaneous administrations of monosodium glutamate (MSG) to neonatal animals result in obesity and induce the toxicity on the central nervous system, and furthermore, have an effect on entero-pancreatic hormone. The effect of MSG on the cell turnover of organs, especially the pancreas, has received little attention until now. This study was designed to examine the effect of MSG on pancreatic cell turnover by immunohistochemistry and [(3)H]thymidine autoradiography. RESEARCH METHODS AND PROCEDURES: Male JcI-ICR strain mice were SC injected with MSG (2 mg/g body weight daily) for 5 days after birth, received 112 repeated injections of [(3)H]thymidine at 6-hour intervals for 28 days after birth, and then were killed immediately thereafter, or 30, 60, or 120 days after the last injection. Autoradiography was performed on sections immunostained for glucagon, insulin, and somatostatin. RESULTS: After continuous labeling, most pancreatic cells were labeled, and thereafter, labeling of cells decreased in control and MSG-treated mice. The mean grain counts of acinar cells in MSG-treated mice decreased more slowly than those in control mice. On the other hand, those of islet cells, including glucagon, insulin, and somatostatin cells, decreased more rapidly in MSG-treated mice than those in control mice. DISCUSSION: Cell turnover of acinar cells was decelerated and that of islet cells including glucagon, insulin, and somatostatin cells was accelerated in MSG-treated mice pancreas. MSG-induced hypothalamic lesions exert the contrary influences on the cell turnover of acinar and islet cells.