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991.
Previous studies have demonstrated that a natural coumarin compound esculetin (Esc) possesses antioxidant, anti-tumor, and anti-inflammation activities and rescues cultured primary neurons from NMDA toxicity. In this study, we investigated the neuroprotective effects of Esc on cerebral ischemia/reperfusion (I/R) injury in a middle cerebral artery occlusion model in mice. Esc (20 μg) was administered intracerebroventricularly at 30 min before ischemia. We found that Esc significantly reduced infarct volume and decreased neurological deficit scores after 75 min of ischemia and 24 h of reperfusion. Post-treatment of Esc still provided neuroprotection even when Esc was administered after 4 h of reperfusion. Our data also indicated that intraperitoneal administration of Esc showed protective effects on cerebral I/R injury in a dose-dependent manner. We further explored the protective mechanisms of Esc on cerebral I/R injury and found that Esc decreased cleaved caspase 3 level, a marker of apoptosis. Finally, our data demonstrated that Esc exerted its anti-apoptotic activity by up-regulating the expression of Bcl-2 and down-regulating the expression of Bax, two apoptosis-related proteins. Because of its clinical use as an anticoagulant and its safety profile, Esc may have a therapeutic potential for the treatment of stroke in the future clinical trials. 相似文献
992.
The proliferation of pulmonary artery smooth muscle cells (PASMCs) plays a role in pulmonary vascular remodeling (PVR). Recently, it was shown that vascular smooth muscular cell phenotype modulation is important for their proliferation in other diseases. However, little is known about the role of human PASMC phenotype modulation in the proliferation induced by hypoxia and its molecular mechanism during PVR. In this study, we found using primary cultured human PASMCs that hypoxia suppressed the expression of endogenous PKGIα, which was reversed by transfection with a recombinant adenovirus containing the full-length cDNA of PKGIα (Ad-PKGIα). Ad-PKGIα transfection significantly attenuated the hypoxia-induced downregulation of the expression of smooth muscle α-actin (SM-α-actin), myosin heavy chain (MHC) and calponin in PASMCs, indicating that hypoxia-induced phenotype modulation was blocked. Furthermore, flow cytometry and 3H-TdR incorporation demonstrated that hypoxia-induced PASMC proliferation was suppressed by upregulation of PKGIα. These results suggest that enhanced PKGIα expression inhibited hypoxia-induced PASMC phenotype modulation and that it could reverse the proliferation of PASMCs significantly. Moreover, our previous work has demonstrated that Akt protein is activated in the process of hypoxia-induced proliferation of human PASMCs. Interestingly, we found that Akt was not activated by hypoxia when PASMC phenotype modulation was blocked by Ad-PKGIα. This result suggests that blocking phenotype modulation might be a key up-stream regulatory target. 相似文献
993.
Purpose
A number of studies reported on associations of single nucleotide polymorphisms (SNPs) present in chromosome 9p21 with early-onset coronary artery disease (CAD). The present study was then undertaken to perform a meta-analysis of all the results published to date.Methods
All studies of the 9p21 association with early-onset CAD that were published between 2007 and 2012 were retrieved from the PubMed database. RevMan 5.0 software was used to perform meta-analysis of the data that fulfilled the criteria for our meta-analysis. The effect size of four SNPs in the 9p21 region on early-onset CAD risk was assessed based on the odds ratios (ORs) with calculation of 95% confidence interval (CI).Results
A total of 7123 subjects from 7 case–control studies were genotyped. Meta-analysis demonstrated disease association for rs2383207 (OR = 0.79, 95% CI 0.71–0.88, P < 0.0001), rs2383206 (OR = 1.17, 95% CI 1.10–1.25, P < 0.00001), rs10757278 (OR = 1.28, 95% CI 1.15–1.42, P < 0.00001), and rs10757274 (OR = 1.17, 95% CI 1.08–1.33, P = 0.02).Conclusion
Genetic variation in the chromosome 9p21 region may contribute to the etiology of early-onset CAD although their effect size is rather small. 相似文献994.
目的大鼠自主呼吸情况下,快捷、简便地建立大鼠急性心肌梗死模型。方法 180~220gSD大鼠60只,于胸骨左缘第4-5肋间隙切开皮层作荷包缝合,逐层钝性分离肌肉,挤出心脏,快速结扎左冠状动脉前降支(LAD)后,送回心脏同时挤压胸廓,拉紧荷包以建立心肌梗死模型。记录结扎前、结扎后3h心电图;结扎3h后取出心脏,冰冻切片TTC染色。结果 50只大鼠成功建立心肌梗死模型,模型成功率为83.33%。心电图显示结扎冠脉后出现R波峰降低,ST段拱背抬高及ST-T融合,TTC染色后左心室出现明显灰白色梗死区。结论本方法可在大鼠自主呼吸情况下,较短的时间内以简便的手术、较小的创伤建立大鼠急性心肌梗死模型。 相似文献
995.
PDGF-BB多肽刺激肺动脉平滑肌细胞PDGFmRNA表达 总被引:1,自引:1,他引:1
应用地高辛(Digoxigenin)标记的血小板源性生长因子(PDGF)A和PDGFB链cDNA探针,原位检测了PDGFBB多肽对单层培养的肺动脉平滑肌细胞PDGF基因表达的影响。结果表明,无血清培养的肺动脉平滑肌细胞内PDGFA和PDGFB链mRNA阳性表达颗粒稀少,PDGFBB多肽培养的肺动脉平滑肌细胞PDGFA和PDGFB链mRNA阳性表达颗粒增多,较密集的分布于整个细胞内。全自动图像分析结果显示,PDGFA和PDGFB链mRNA表达,PDGFBB培养组分别为无血清培养组的174倍和17倍,差异显著(P<001)。本研究结果提示,PDGFBB多肽能刺激肺动脉平滑肌细胞PDGFmRNA表达,促进其分泌,在慢性低氧性肺动脉高压血管平滑肌细胞增殖中具有重要作用 相似文献
996.
997.
Eun-Jung Rhee Shriram Nallamshetty Jorge Plutzky 《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2012,1821(1):230-240
Retinoids, the metabolically-active structural derivatives of vitamin A, are critical signaling molecules in many fundamental biological processes including cell survival, proliferation and differentiation. Emerging evidence, both clinical and molecular, implicates retinoids in atherosclerosis and other vasculoproliferative disorders such as restenosis. Although the data from clinical trials examining effect of vitamin A and vitamin precursors on cardiac events have been contradictory, this data does suggest that retinoids do influence fundamental processes relevant to atherosclerosis. Preclinical animal model and cellular studies support these concepts. Retinoids exhibit complex effects on proliferation, growth, differentiation and migration of vascular smooth muscle cells (VSMC), including responses to injury and atherosclerosis. Retinoids also appear to exert important inhibitory effects on thrombosis and inflammatory responses relevant to atherogenesis. Recent studies suggest retinoids may also be involved in vascular calcification and endothelial function, for example, by modulating nitric oxide pathways. In addition, established retinoid effects on lipid metabolism and adipogenesis may indirectly influence inflammation and atherosclerosis. Collectively, these observations underscore the scope and complexity of retinoid effects relevant to vascular disease. Additional studies are needed to elucidate how context and metabolite-specific retinoid effects affect atherosclerosis. This article is part of a Special Issue entitled: Retinoid and Lipid Metabolism. 相似文献
998.
John D. Brunzell Alberto Zambon Samir S. Deeb 《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2012,1821(3):365-372
Increased or decreased hepatic lipase (HL) activity has been associated with coronary artery disease (CAD). This is consistent with the findings that gene variants that influence HL activity were associated with increased CAD risk in some population studies but not in others. In this review, we will explain the conditions that influence the effects of HL on CAD. Increased HL is associated with smaller and denser LDL (sdLDL) and HDL (HDL3) particles, while decreased HL is associated with larger and more buoyant LDL and HDL particles. The effect of HL activity on CAD risk is dependent on the underlying lipoprotein phenotype or disorder. Central obesity with hypertriglyceridemia (HTG) is associated with high HL activity that leads to the formation of sdLDL that is pro-atherogenic. In the absence of HTG, where large buoyant cholesteryl ester-enriched LDL is prominent, elevation of HL does not raise the risk for CAD. In HTG patients, drug therapy that decreases HL activity selectively decreases sdLDL particles, an anti-atherogenic effect. Drug therapy that raises HDL2 cholesterol has not decreased the risk for CAD. In trials where inhibition of cholesterol ester transfer protein (CETP) or HL occurs, the increase in HDL2 most likely is due to inhibition of catabolism of HDL2 and impairment of reverse cholesterol transport (RCT). In patients with isolated hypercholesterolemia, but with normal triglyceride levels and big-buoyant LDL particles, an increase in HL activity is beneficial; possibly because it increases RCT. Drugs that lower HL activity might decrease the risk for CAD only in hypertriglyceridemic patients with sdLDL by selectively clearing sdLDL particles from plasma, which would override the potentially pro-atherogenic effect on RCT. This article is part of a Special Issue entitled Advances in High Density Lipoprotein Formation and Metabolism: A Tribute to John F. Oram (1945-2010). 相似文献
999.
目的:探讨对终末期肾病患者行甲状旁腺切除对颈动脉钙化的影响.方法:选择我院2009年10月至2010年12月收治的20例继发性甲状旁腺功能亢进的终末期肾病患者,行甲状旁腺切除术,对患者术前、术后进行颈动脉彩超检查颈动脉钙化情况,并将患者术前、术后的血钙、血磷、钙磷乘积、PTH、C反应蛋白、血红蛋白、白蛋白等指标进行比较.结果:与术前比较,术后患者颈动脉钙化斑块有明显减少,血钙、血磷、钙磷乘积、PTH、C反应蛋白均明显降低,差异性有显著(P<0.05);血红蛋白较术前明显升高(P<0.05).结论:切除甲状旁腺(PTX)能安全有效的降低甲状旁腺素水平、改善钙磷代谢紊乱,并控制颈动脉钙化的进展. 相似文献
1000.
李维琴王兴胡晓燕陈丽霞常君 《现代生物医学进展》2012,12(18):3544-3546
目的:旨在探讨血清脂肪因子chemerin水平与代谢综合征患者合并冠心病的相关性。方法:共纳入116名代谢综合征患者,将所有患者分为两组,合并冠心病组(CAD+,n=47)及未合并冠心病组(CAD-,n=69),使用酶联免疫吸附(ELISA)法测量每组血清的血清chemerin水平。结果:CAD+组患者的血清chemerin水平较CAD-组患者显著升高(129.83±29.18 vs 94.01±23.54 ng/mL;P<0.01),多元Logistic回归分析结果显示血清chemerin水平与代谢综合征患者合并冠心病存在独立相关性(优势比1.565,95%可信区间1.104-2.876;P<0.05)。结论:血清chemerin水平是代谢综合征患者合并冠心病的独立危险因子,血清chemerin可能是预测代谢综合征患者发生冠心病风险的重要的生物学标记物。 相似文献