MiRNA在动脉粥样硬化血管新生中的作用

在动脉粥样硬化斑块的发展过程中,血管新生是一个重要的影响因素,局部新生血管和斑块稳定性密切相关。随着斑块内新生血管数量的增加,斑块内脂质和各种炎细胞堆积,最终导致基质降解,纤维帽变薄,斑块破裂,进而引发严重的心血管事件。mi RNA的研究越发地让我们认识到,mi RNA不仅在肿瘤疾病领域,在动脉粥样硬化领域中也发挥着极其重要的作用。近年来,在心血管系统中发现多种可能与动脉粥样硬化相关的mi RNA,可能为动脉粥样硬化的早期诊断和治疗选择提供了新的线索。     

血管新生与冠心病治疗性血管生成

继冠状动脉再通术后,治疗性血管新生成为冠心病基础与临床研究的热点,但血管新生的影响因素复杂,治疗性血管新生所得到的临床试验结果也不尽一致。现对此做一综述,结合血管新生的影响因素,分析了一些增强血管新生疗效的方法和降低疗效的--r~g原因,总结了冠心病治疗性血管生成临床研究进展,以期有利于冠心病治疗性血管新生成基础与临床研究。     

新生滋养血管在动脉粥样硬化斑块进展中的作用

滋养血管新生作为动脉粥样硬化斑块发生发展中的关键环节已受到普遍关注,在动脉内膜发生缺血缺氧或炎症时可诱发滋养血管新生,并通过白细胞征募和斑块内出血等机制影响斑块的稳定性.     

新生滋养血管在动脉粥样硬化形成中的作用及临床意义

动脉粥样硬化(As)病变的主要临床危险性在于斑块的不稳定性、易损性。斑块内新生滋养血管(VV)具有结构缺陷,其脆性大、渗漏性高,容易破裂出血,促进炎症反应,也为血细胞及血液可溶性成分进入斑块提供通道,促进As斑块的形成,并且与斑块内出血、斑块破裂及临床心脑血管事件的发生密切相关。深入研究新生滋养血管的功能及关键信号途径在As中的作用,有望从根本上阻止稳定斑块发展为易损斑块,或者阻止不稳定斑块破裂及其并发症的发生。     

粥样斑块发生发展过程中炎症和新生内膜血管之间的关系

目的为研究在控制炎症水平的情况下内膜新生血管在动脉粥样斑块发生、发展中所起到的具体作用。方法高脂饮食8周造成大鼠动脉粥样硬化（AS）模型,然后使用阿司匹林抑制AS大鼠的基础炎症水平,分别给予内皮抑素和血管内皮生长因子165（VEGF165）两种不同方法处理大鼠,8周后比较血脂、胸主动脉形态学、以及检测CD31表达水平以计算内膜新生血管的数量。结果模型组的血脂水平高于空白对照组（P<0.05）;粥样斑块内部的新生血管数量VEGF165+阿司匹林组>单纯模型对照组>阿司匹林组>内皮抑素+阿司匹林组>空白对照组（P<0.05）;阿司匹林组、内皮抑素+阿司匹林组和VEGF165+阿司匹林组的内膜面积/中膜面积的比值（IA/MA）差异无显著性,但高于单纯模型对照组（P<0.05）。结论在用阿司匹林抑制AS模型大鼠基础炎症的情况下,VEGF165和内皮抑素对血管内膜生成的影响无显著差异。     

血管抑素对新生血管的作用及其机制研究进展

血管抑素作为近年来发现的一种血管生成抑制剂,对肿瘤及眼部新生血管具有较强的抑制作用,该文就其在新生血管中的作用作简单综述。     

肝纤维化与血管新生相关性的研究进展

肝纤维化是许多慢性肝病的共同病理过程,肝细胞发生坏死及炎症刺激时,肝脏中胶原蛋白等细胞外基质的增生与降解失去平衡,导致肝脏内纤维结缔组织异常沉积,轻者称为纤维化,若进一步发展引起肝小叶改建、假小叶和结节形成,则进入肝硬化。在我国乙型肝炎,尤其是慢性活动性肝炎患者中,10%～15%的患者可能在5～10年内发展为肝     

血管生长因子在冠心病治疗性血管新生中的应用

血管生长因子在血管新生过程中起着重要作用.大量的动物研究显示在给予血管生长因子后能够有效地促进缺血心肌的血管新生,改善局部血流灌注,提高心功能.但由于临床Ⅱ期试验未取得预期的阳性结果,给治疗性血管新生的应用带来了新的挑战,众多问题有待进一步优化和解决.     

血管生长因子在冠心病治疗性血管新生中的应用

血管生长因子在血管新生过程中起着重要作用。大量的动物研究显示在给予血管生长因子后能够有效地促进缺血心肌的血管新生,改善局部血流灌注,提高心功能。但由于临床Ⅱ期试验未取得预期的阳性结果,给治疗性血管新生的应用带来了新的挑战,众多问题有待进一步优化和解决。     

Epigenetic regulation of N6-methyladenosine modifications in obesity

Obesity is a serious health issue in the world and is related to a higher risk of suffering metabolic diseases. Understanding the molecular basis of obesity is critical to identify new targets to treat obesity and obesity-associated metabolic diseases. N6-methyladenosine (m6A) modification is the most common form of ribonucleic acid modification, which has attracted increasing interest of researchers in recent years, as it is reported that m6A has vital functions in diseases and everyday life activities. Recent studies showed that m6A modification was decreased in obese adipose tissue, and appeared to play a regulatory role in many obesity-associated biological processes, including adipogenesis, lipid metabolism and insulin resistance. In this review, we discussed the emerging advances in m6A modification in obesity to provide a novel therapeutic strategy for fighting against obesity.     

WNT10B mutations in human obesity

Aims/hypothesis Recent studies suggest that wingless-type MMTV integration site family, member 10B (WNT10B) may play a role in the negative regulation of adipocyte differentiation in vitro and in vivo. In order to determine whether mutations in WNT10B contribute to human obesity, we screened two independent populations of obese subjects for mutations in this gene. Subjects and methods We studied 96 subjects with severe obesity of early onset (less than 10 years of age) from the UK Genetics of Obesity Study and 115 obese Italian subjects of European origin. Results One proband with early-onset obesity was found to be heterozygous for a C256Y mutation, which abrogated the ability of WNT10B to activate canonical WNT signalling and block adipogenesis and was not found in 600 control alleles. All relatives of the proband who carried this allele were either overweight or obese. Three other rare missense variants were found in obese probands, but these did not clearly cosegregate with obesity in family studies and one (P301S), which was found in three unrelated subjects with early-onset obesity, had normal functional properties. Conclusions/interpretation These mutations represent the first naturally occurring missense variants of WNT10B. While the pedigree analysis in the case of C256Y WNT10B does not provide definitive proof of a causal link of this variant with obesity, the finding of a non-functioning WNT10B allele in a human family affected by obesity should encourage further study of this gene in other obese populations.     

调节性T细胞亚群在肥胖发病中的作用

CD4+CD25+Foxp3+调节性T细胞(Treg细胞)与效应性T细胞数量和(或)功能状态的失衡触发炎性反应.在健康小鼠及人体内脏脂肪组织中Treg细胞丰富存在,而在肥胖小鼠及人体脂肪中Treg细胞的数量及功能状态存在异常.Treg细胞亚群的异常将直接造成脂肪组织的慢性低度炎性反应状态.由于慢性低度炎性反应状态在肥胖及肥胖相关的胰岛素抵抗的发生、发展中扮演重要角色,Treg细胞将成为其未来研究的一个新热点.     

昼夜节律变化在肥胖和糖尿病发病中的作用

不断增长的临床资料表明,影响昼夜节律的现代生活方式增加肥胖和糖尿病的发病风险.最近的遗传性动物模型也进一步证实了昼夜节律与代谢之间的密切相关.昼夜节律生物钟不仅仅存在于中枢神经系统,还存在于机体几乎所有细胞,形成不同层次的昼夜节律系统.分子生物钟通过长期的进化,以使机体能够预见和准备适应环境的每天变化,通过驱动基因表达和酶的活性调控细胞和组织功能.目前在这一领域的基础科学以惊人的速度向前发展,有望不断揭示昼夜节律钟与代谢之间联系的机制,这对于理解糖尿病和肥胖等代谢性疾病的生理和病理机制都有重要意义,并为其防治提供理论基础.     

Wnt信号通路在脂肪形成中的作用

Wnt信号通路在细胞增殖、分化、发育及成熟组织的稳态和自我更新等方面发挥重要的调控作用.Wnt蛋白、多种抑制剂和小RNA (microRNAs)可以调节白色脂肪组织中的脂肪形成;Wnt信号通路在棕色脂肪形成中也发挥调节作用.此外,该通路可决定肥胖易感性,Wnt10b和LRP5基因多态性可能与欧洲人的肥胖患病风险相关.通...     

Effect of Ichnocarpus frutescens (L.) R. Br. hexane extract on preadipocytes viability and lipid accumulation in 3T3-L1 cells

ObjectiveTo investigate the crude extracts of Ichnocarpus frutescens (I. frutescens) for antiobesity effect.MethodsLeaves of I. frutescens were sequentially extracted with hexane, ethyl acetate, and methanol and their effect on viability of 3T3-L1 preadipocytes were evaluated. Based on this the apoptosis on preadipocytes was confirmed by DNA fragmentation and LDH (Lactate dehydrogenase) leakage assays. Anti-adipogenesis was performed by oil red O (ORO) staining and free glycerol release in the medium of differentiated adipocytes.ResultsThe hexane extract of I. frutescens (IFHE) inhibited cell viability in a time- and dose-related manner. An increased release of LDH, as a marker of membrane integrity, was observed at a dose of 200 μ g/mL. The discontinuous DNA fragments on agarose gel electrophoresis showed the apoptotic effect of the IFHE. Morphological observations of cells stained with ORO showed a decrease in cellular lipid content at the concentrations tested compared to the induced control cells. In the experiment of lipolytic activity, treatment with IFHE enhanced glycerol secretion with the rates of approximately 28%, 55%, and 46% at the concentrations of 100, 200 and 300 μ g/mL, respectively.ConclusionsThe observed properties clearly revealed the medicinal property of I. frutescens in the treatment of obesity.     

Role of microRNAs in obesity and the metabolic syndrome

Obesity and the metabolic syndrome are major public health concerns, and present a formidable therapeutic challenge. Many patients remain recalcitrant to conventional lifestyle changes and medical therapies. Bariatric surgery has made laudable progress in the treatment of obesity and its related metabolic disorders, yet carries inherent risks. Unravelling the molecular mechanisms of metabolic disorders is essential in order to develop novel, valid therapeutic strategies. Mi(cro)RNAs play important regulatory roles in a variety of biological processes including adipocyte differentiation, metabolic integration, insulin resistance and appetite regulation. Investigation of these molecules and their genetic targets may potentially identify new pathways involved in complex metabolic disease processes, improving our understanding of metabolic disorders and influence future approaches to the treatment of obesity. This review discusses the role of miRNAs in obesity and related components of the metabolic syndrome, and highlights the potential of using miRNAs as novel biomarkers and therapeutic targets for these diseases.     

白藜芦醇改善高脂诱导老龄小鼠肥厚性肥胖作用的研究

目的探讨白藜芦醇对老龄小鼠肥胖的影响及其可能的作用机制.方法分别将32周龄和48周龄小鼠随机分为3组:正常对照组进食普通饲料,每天灌胃1次0.3 ml生理盐水;高脂饮食处理组进食高脂饲料(含有21%脂肪和1.25%胆固醇),每天灌胃1次0.3 ml生理盐水;高脂饮食加白藜芦醇组进食高脂饲料,每天灌胃1次白藜芦醇(22.4 mg/kg,分散于0.3 ml生理盐水中).12周后称量各组小鼠体重,并进行脂肪组织取材及称重;采用酶联免疫吸附试验检测小鼠血浆瘦素浓度;通过实时荧光定量聚合酶链式反应方法检测小鼠肥厚性肥胖相关指标.结果高脂饮食加白藜芦醇组老龄小鼠体重及皮下脂肪含量分别为(34.43±3.23)g和(3.21±1.58)%,较高脂饮食组老龄小鼠(53.16±2.16)g和(4.86±0.64)%有明显下降(均P<0.01),并与普通饮食中年小鼠数据接近;与中年小鼠比较,白藜芦醇对高脂饮食老龄小鼠瘦素的抑制作用更为显著,高脂饮食加白藜芦醇组老龄小鼠血浆瘦素浓度(0.015±0.009)g/L,较高脂饮食组老龄小鼠(0.100±0.027)g/L明显下降,且低于普通饮食的老龄小鼠(F=19.85,P=0.001),与普通饮食中年小鼠相接近;白藜芦醇可以显著增加高脂饮食老龄小鼠皮下脂肪组织过氧化物酶体增殖物激活受体γ(PPARγ)和葡萄糖转运蛋白4(GLUT4)的表达,并降低肿瘤坏死因子-α(TNF-α)的表达(F=10.79、9.31、7.02,P=0.003、0.006,0.010).结论白藜芦醇可以显著改善老龄小鼠肥厚性肥胖,抑制瘦素分泌和上调PPARγ表达可能是其作用的关键机制.     

增食欲素干预单纯性肥胖的作用及机制

增食欲素作为一种调节进食与能量代谢等生理功能的重要中枢神经肽,与多种神经递质构成中枢调控网络,促进进食,抑制胃肠蠕动,增强胃酸分泌.增食欲素对机体自发运动有向上调节作用,且比促食作用更明显,从而增加机体非运动活动产热,影响休息/非休息能量消耗比.此外增食欲素还能提高褐色脂肪组织的生热作用,共同增强机体能量消耗,干预肥胖发展.     

肥胖对高血压左室肥厚的影响

目的 :探讨肥胖对高血压左室肥厚 (LVH)的影响及两者之间的关系。方法 :应用超声心动图检测4 6例高血压肥胖患者左室心肌重量 (LVM)及左室心肌重量指数 (LVMI) ,并与 4 8例高血压非肥胖患者及 19例正常对照者进行比较 ,了解高血压伴肥胖者LVH的发生率和相对危险度。结果 :高血压肥胖患者的LVM明显高于高血压非肥胖者和正常对照者 [(2 30 .18± 6 3.99) g∶(2 0 0 .4 8± 5 9.0 4 ) g和 (16 1.5 8± 38.5 4 ) g ,P <0 .0 5 ,P<0 .0 1];高血压肥胖者的LVMI也较正常对照组明显增加 [(12 7.81± 34.4 4 )∶(98.0 1± 2 1.6 5 ) ,P <0 .0 5 ],但与高血压非肥胖组 (118.86± 33.2 3)相比无统计学差异 (P >0 .0 5 ) ;高血压肥胖患者LVH检出率也较高血压非肥胖者明显增高 (6 0 .9%∶39.6 % ,P <0 .0 5 ) ,前者发生LVH的相对危险度是后者的 2 .37倍。结论 :肥胖对高血压LVH有促进作用。