内脂素与动脉粥样硬化的关系

近年来,研究者发现了一种新的脂肪因子——内脂素,它主要来源于内脏脂肪,具有类胰岛素样作用。最近,国内外许多研究发现,内脂素与易损斑块形成、血管新生、血管炎症发生、内皮功能损伤、血管平滑肌细胞的增生及变性等密切相关,有进一步研究的必要性和重要意义。现就其国内外研究现状进行概述。     

冠心病患者血浆内脂素及基质金属蛋白酶-9的相关性及临床意义

目的探讨冠心病患者血浆内脂素及基质金属蛋白酶-9（MMP-9）的相关性及临床意义。方法选取2010年2月至2011年11月我院收治的冠心病患者75例,其中急性冠脉综合征（ACS）47例,稳定型心绞痛（SAP）28例,单支血管病变25例,双支病变26例,三支病变24例。选取同期健康体检者20例作为对照组,采用酶联免疫吸附法测定血浆内脂素及MMP-9水平。结果冠心病患者血浆内脂素及MMP-9水平均显著高于对照组（P〈0.05）,且ACS组显著高于SAP组（P〈0.05）。单支组、双支组、三支组患者血浆内脂素及MMP-9水平均显著高于对照组（P〈0.05）,且3组之间比较差异均具有统计学意义（P〈0.05）,血浆内脂素水平与MMP-9呈显著正相关（P〈0.05）。结论冠心病患者血浆内脂素水平与MMP-9密切相关,对预测冠状动脉病变严重程度具有重要临床意义。     

不同糖耐量个体血浆内脂素水平的变化

目的探讨不同糖耐量人群血浆内脂素(visfatin)水平变化及其与体重指数(BMI)、腰臀比(WHR)、血糖、血浆胰岛素水平等的关系。方法采用酶联免疫法测定了2型糖尿病(DM)、糖耐量受损(IGT)患者和正常健康人空腹和糖负荷后2h血浆内脂素水平,并分析血浆内脂素与BMI、WHR、胰岛素抵抗指数(HOMA-IR)、血脂、血糖、血浆胰岛素和游离脂肪酸(FFA)水平等的关系。结果(1)2型DM患者空腹和糖负荷后2h血浆内脂素水平明显低于正常对照组[(11.63±7.48)μg/L vs(16.82±6.06)μg/L和(12.02±6.86)μg/L vs(16.26±7.78)μg/L,均P＜0.05],IGT组内脂素水平介于2型DM和对照组之间；肥胖组血浆内脂素水平较非肥胖组有升高趋势；(2)相关性研究显示,血浆内脂素水平与WHR呈正相关(r=0.42,P＜0.01),与糖负荷后2h血糖(2hPG)和HbA_(IC)呈明显负相关(r=-0.33,P＜0.01和r=～0.25,JP＜0.05)；(3)多元线性逐步回归分析表明WHR、HbA_(IC)空腹血糖、2hPG、高密度脂蛋白胆固醇分别是影响血浆内脂素水平的独立相关因素。结论血浆内脂素水平与糖代谢状态有关,并可能在肥胖和2型糖尿病的发生和发展中具有一定的作用。     

内肥素与儿童青少年肥胖、非酒精性脂肪肝的关联研究

目的 探讨血清内肥素与儿童青少年肥胖、非酒精性脂肪肝(NAFLD)的关联.方法 采用双抗体夹心ELISA法,测定69名体重正常无NAFLD和106名肥胖儿童青少年(肥胖无NAFLD 49名及合并NAFLD 57名,其中轻度42名、中重度15名)的血清内肥素水平.结果 体重正常组与肥胖组血清内肥素水平分别为( 1.75±0.37)、(1.71±0.37)ng/ml,差异无统计学意义(P=0.455);肥胖儿童青少年血清内肥素水平随着脂肪肝程度的加重而上升[肥胖无NAFLD组为(1.59±0.36)ng/ml、肥胖合并轻度NAFLD组为(1.74±0.36) ng/ml、肥胖合并中重度NAFLD组为( 1.97±0.36)ng/ml,三者之间差异有统计学意义(P＜0.05)],与年龄(^β=-0.326,P=0.000)、丙氨酸转氨酶活性(^β=0.286,P=0.004)相关,不同程度NAFLD者内肥素水平差异有统计学意义(^β=0.246,P=0.014).结论 肥胖儿童青少年中血清内肥素水平与NAFLD相关.     

NF-κB介导大鼠肾小球系膜细胞Visfatin对促纤维化因子和细胞外基质表达的影响

目的观察大鼠肾小球系膜细胞中内脏脂肪素(Visfatin)对促纤维化因子和细胞外基质(ECM)表达的影响并探讨核因子-κB(NF-κB)在此过程中的作用。方法分别构建Visfatin表达质粒及Visfatin RNAi质粒,将细胞分为八组:A组:正常糖对照组;B组:正常糖+NF-κB特异性抑制剂吡咯烷二硫基甲酸酯(PDTC)组;C组:过表达Visfatin组;D组:过表达Visfatin+PDTC组;E组:空白表达载体组;F组:空白表达载体+PDTC组;G组:Visfatin RNAi组;H组:空白沉默载体组。比较过表达或沉默Visfatin前后促纤维因子及细胞外基质基因及蛋白表达的变化。用Realtime-PCR方法检测转录生长因子β(TGF-β)、结缔组织生长因子(CTGF)、纤维蛋白溶解酶原激活物抑制剂(PAI-1)、纤维连接蛋白(FN)、I型胶原(Col I)、IV胶原(Col IV)等基因表达的变化,用Western Blot检测Visfatin、CTGF、FN等蛋白的表达,用电泳迁移率变动分析法(EMSA)检测NF-κB活性;以及通过观察PDTC处理对照组、过表达Visfatin组、空白表达载体组前后上述指标的变化。结果大鼠肾系膜细胞过表达Visfatin后,NF-κB活性、Visfatin、TGF-β、CTGF、PAI-1、FN、Col I、Col IV的m RNA表达量及Visfatin、CTGF、FN蛋白表达量显著升高(P0.05)。下调Visfatin表达后,NF-κB活性、Visfatin、TGF-β、CTGF、PAI-1、FN、Col I、Col IV的m RNA表达量及Visfatin、CTGF、FN蛋白表达量均显著降低(P0.05)。PDTC处理的各组,NF-κB活性、TGF-β、CTGF、PAI-1、FN、Col I、Col IV表达量与对应的未经PDTC处理组相比显著降低(P0.05)。结论在大鼠肾小球系膜细胞中,Visfatin可通过NF-κB通路诱导促纤维化因子和细胞外基质的表达。     

血清 C-反应蛋白（CRP）、内脂素、脂联素在 2 型糖尿病肾病不同时期的变 化

目的研究血清C-反应蛋白（CrtP）、内脂素、脂联素在2型糖尿病肾病不同时期的具体变化情况。方法从2010年3月-2013年3月该院接受2型糖尿病肾病治疗的患者中随机选择194例作为研究组进行分析,根据患者具体的尿清蛋白排泄率分为3组,其中正常蛋白尿组70例,微量蛋白尿组60例,大量蛋白尿组64例;并选择70例经体检健康状况良好的正常者作为对照组。采用酶联免疫吸附法检测所有受检者体内的内脂素、脂联素具体水平,并采用免疫比浊法测定血清C-反应蛋白（CRP）。另外对所有受检者的空腹血糖值,高、低密度脂蛋白胆固醇含量等先关指标进行具体检测,并比较研究组和对照组之间的差异。结果研究组患者体内的血清内脂素和血清C-反应蛋白（cRP）水平明显高于对照组,差异有统计学意义（P〈0．05）。正常蛋白尿组的具体血清脂联素含量低于对照组,微量蛋白尿组和大量蛋白尿组患者的血清脂联素高于对照组,差异有统计学意义（P〈0．05）。结论血清内脂素、脂联素和血清C-反应蛋白（CRP）极有可能参与到了2型糖尿病肾病发生、发展的整个过程．联合对参者的具体水平进行检测和分析可能会对评估早期糖尿病肾病有重要的帮助作用。     

慢性心力衰竭患者血浆内脏脂肪素水平及其影响因素的研究

目的观察慢性左心衰竭患者的血浆内脏脂肪素水平,探讨其与糖脂代谢参数和高敏C反应蛋白（hs—CRP）的关系。方法将50例慢性左心功能不全患者（心力衰竭组）根据超声心动图左心室射血分数（LVEF）分成两亚组：轻度心功能不全亚组（35％〈LVEF≤45％）25例,重度心功能不全亚组（LVEF≤35％）25例;对照组（LVEF〉50％）24例,检测并比较各组hs—CRP、内脏脂肪素、血脂、血糖等指标。结果心力衰竭组内脏脂肪素较对照组降低（5．84-221ng／mlVS8．5±2．4ng／ml,P〈0．01）;轻度、重度心功能不全亚组及对照组比较．内脏脂肪素、hs—CRP、血糖、HOMAIR、HDL—C差异均有统计学意义（P〈0．05或0．01）;内脏脂肪素与LVEF呈正相关（r=0．49,P〈001）,与hs—CRP呈负相关（r=-0．30,P〈0．01）。结论心力衰竭患者的血清内脏脂肪素显著降低,此结果独立于年龄、性别、BMI和代谢参数。     

Role of adipocytokines and its correlation with endocrine pancreatic function in patients with pancreatic cancer

IntroductionSome authors suggest that adipocytokines contribute to the induction of pancreatic carcinogenesis as well as the development of endocrine insufficiency.AimsWe evaluate the circulating concentrations of leptin, resistin and visfatin in patients with newly diagnosed pancreatic cancer (PC) and relationship between serum adipocytokines level and clinicopathological features of PC. Moreover the usefulness of those adipocytokines as possible biomarkers of endocrine pancreatic function in PC has been assessed.MethodsThe pilot study group consisted of 45 individuals (mean age 65.6 ± 11.5 years, BMI 21.8 ± 3.4 kg/m²) with newly diagnosed PC (within last 1–3 months) and 13 healthy individuals with age, gender and BMI matched to the study group. Among PC patients 18 (40%) had recently diagnosed diabetes. Fasting plasma leptin, resistin, visfatin concentrations were determined with ELISA (R&D Systems, Phoenix Pharmaceuticals) and insulin by RIA (DakoCytomation).ResultsPatients with PC as compared to controls had significantly lower plasma leptin (40.6 ± 21.3 vs 63.2 ± 16.3 pg/mL; p < 0,0008). In contrast PC patients showed more than six fold higher level of resistin (126.2 ± 143.2 vs 18.9 ± 7.2 ng/mL; p < 0.009) than controls. The median plasma visfatin was 2.8 ± 1.8 ng/mL, which was not significantly different from the controls (3.8 ± 1.1 ng/mL). When PC patients with and without diabetes were considered separately, plasma leptin concentrations among nondiabetic patients were slightly, but not significantly higher (44.6 ± 21.0) as compared to diabetics (34.5 ± 20.7). Moreover there was no difference between visfatin and resistin level in PC, among patients with and without diabetes. No significant differences between serum level of leptin, visfatin and resistin and age, gender, BMI, smoking status, tumor localization, distant metastases and pain has been found.ConclusionThe results of this study confirm previous findings that patients with newly diagnosed pancreatic cancer are characterized with lower level of leptin. This pilot study showed significantly higher resistin concentrations in patients with PC in comparison to healthy controls, which may be helpful in PC early diagnosis. Changes in leptin and resistin level in PC are not likely related to endocrine disorders.     

Association of genetic variability in selected regions in visfatin (NAMPT) gene with anthropometric parameters and dietary composition in obese and non-obese Central-European population

AimsVisfatin (NAMPT/PBEF) is a recently identified adipocytokine which harbors strong insulin-mimetic activity and was reported to be associated with obesity. However, nothing is known about whether visfatin is related to specific nutritional behavior which may result in obesity development. This is the first study focusing on genetic variability of the visfatin gene and its association with circulating visfatin, anthropometric parameters and dietary composition.Materials and MethodsWe analyzed a total of 11 exons and adjacent non-coding regions of the NAMPT gene in 20 extremely obese Czech individuals (mean BMI 52.2 ± 5.0 SD) using direct sequencing and a frequency of rs2302559 was established in the validation cohort of another 605 individuals with completed 7-day food records and complex anthropometric measurements. Serum levels of visfatin, leptin and leptin-receptor were measured in all sequenced individuals and in part of the validation cohort.ResultsThree common polymorphisms were identified, two in non-coding regions (rs78411774 A/C, rs71564769 A/C) and one synonymous SNP in exon 7 (rs2302559 A/G). The rs2302559 showed significant correlation with visfatin serum level throughout the entire study cohort (p < 0.001); there was a significant tendency toward higher visfatin levels in G allele carriers with GG homozygotes having the highest visfatin serum levels. Furthermore, a negative correlation was observed between visfatin and leptin serum level (p = 0.01). No association between investigated SNPs and anthropometric parameters or native dietary composition was observed.ConclusionThis is the first study to demonstrate that the rs2302559 polymorphism in the PBEF gene is related to circulating levels of visfatin. As the SNP is synonymous, we hypothesize it might be linked to another SNP in the PBEF gene which controls visfatin serum levels.     

妊娠期糖尿病孕妇血清视黄醇结合蛋白4、内脂素水平的变化及其临床意义

目的探讨妊娠期糖尿病(GDM)患者血清视黄醇结合蛋白4(RBP4)、内脂素水平变化的意义,研究视黄醇结合蛋白4和内脂素与胰岛素抵抗(IR)的相关性。方法采用稳态模型评估法评估正常糖耐量孕妇(NGT)、糖耐量减低孕妇(GIGT)和妊娠期糖尿病孕妇(GDM)的胰岛素抵抗指数,采用酶联免疫吸附法检测所有受试者的空腹血糖(FPG)、空腹胰岛素(FINS)、RBP4和内脂素水平。结果 GDM组和GIGT组血清RBP4、内脂素和胰岛素抵抗指数(HO-MA-IR)均显著高于NGT组(P<0.01)。血清RBP4、内脂素与HOMA-IR均呈显著正相关。结论妊娠期糖尿病患者存在胰岛素抵抗,RBP4、内脂素可影响妊娠期糖尿病患者IR的程度。