脂联素、瘦素与抗精神病药致脂代谢紊乱的相关研究

目的探讨脂联素和瘦素与抗精神病药物致脂代谢紊乱的关系。方法测定血清总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)、脂联素(Adi)和瘦素(leptin)水平,测量身高和体质量,采用聚合酶链扩增和限制性片段长度多态性技术测定脂联素基因多态性。结果 (1)治疗前后对比,BMI、TG、LDL、Leptin和TC水平均显著增高(P<0.01,P<0.05),而Adi水平则显著降低(P<0.05);(2)治疗后,脂联素基因+45G/X基因型者BMI、TG和LDL较治疗前均显著升高(P<0.01),Adi较治疗前则显著下降(P<0.05),而T/X基因型者治疗前后各项指标无显著变化(P>0.05)。结论抗精神病药物可引起体内脂联素水平降低和瘦素水平升高;脂联素+45位G基因是抗精神病药物致脂代谢紊乱的一个危险因素     

脂联素SNP45与2型糖尿病合并脑梗死相关性研究

目的 探讨脂联素SNP45与2型糖尿病及其合并脑血管病变患者之间的关系.方法 对正常对照组(n=64)、单纯2型糖尿病组(n=72)、2 型糖尿病合并脑梗死组(n=51)进行脂联素SNP45基因型测定.结果 SNP45 G/G基因型较T/T基因型个体糖尿病发病率更高,合并大血管病变的可能性也更大,差异均有统计学意义(P<0.05).结论 脂联素基因多态性影响其血清脂联素水平以及糖尿病发生、发展的危险性.     

脂联素基因多态性在抗精神病药对糖脂代谢影响中的意义

目的了解精神分裂症患者的脂联素基因外显子2T45G多态性,并探讨其与应用非典型抗精神病药治疗相关的肥胖以及糖代谢的关系。方法入组患者组125例为应用非典型抗精神病药的精神分裂症患者,正常对照组59例。提取两组基因组DNA,采用聚合酶链式反应-限制片段长度多态性技术,检测脂联素（Adi）基因外显子2T45G多态性和等位基因分布频率。采用免疫酶吸附（ELISA）法分别测定两组血脂,空腹血糖、胰岛素水平计算胰岛素抵抗指数（HOMA-IR）,测量身高、体质量,计算体质量指数（BMI）,并将两组对照比较。结果使用抗精神病药的患者与正常对照组之间脂联素基因型分布及等位基因频率均差异无显著性（χ^2=0．723,0．257;P=0．697,0．613）。携带TG／GG基因型患者的BMI显著高于携带TT型患者（23．53±2．77vs22．37±3．11,P〈0．05）,且携带TG／GG型患者低密度脂蛋白（LDL—C）水平显著高于携带,TT型患者（2．67±0．85vs2．28±1．15,P〈0．05）。携带TT和TG／GG型基因的患者之间的胰岛素抵抗及血脂其他各项差异均无显著性（P〉0．05）;多元线性回归分析示Adi基因外显子2T45G多态性与HOMA—IR并不相关。结论Adi基因外显子2T45G多态性与非典型抗精神病药物治疗相关的脂代谢异常相关,但不是影响血糖代谢障碍的基因危险因子。     

广西百色地区壮族男性人群骨密度与脂联素基因单核苷酸多态性的关系***

背景：脂联素可在骨代谢中发挥重要作用。 目的：观察脂联素基因单核苷酸多态性与广西百色地区壮族男性骨密度的关系。 方法：选取广西百色地区壮族男性跟骨骨量减少患者,采用单碱基延伸的单核苷酸多态性分型技术对广西百色地区302例壮族男性的脂联素基因的5个单核苷酸多态性位点(rs1063539、rs12495941、rs266729和rs3774261)进行了基因分型。 结果与结论：以5个多态性位点作为自变量的多元 Logistic回归检测结果显示,仅rs3774261多态性与跟骨超声振幅衰减显著相关(OR=1.948,95%CI：1.184~3.203,P < 0.01),并独立于骨量减少的传统危险因素。对基因型进行纯合子与杂合子合并后的协方差分析显示,仅rs3774261的AG+GG与AA基因型的跟骨超声振幅衰减值差异有显著性意义(P < 0.05),AG+GG型对骨密度具有一定的保护作用,AA型是骨密度降低的危险因素。结果证实,脂联素基因第2内含子rs3774261位点多态性与中国百色地区壮族男性骨密度有一定关联。     

脂联素在抗精神病药导致体重增加中的作用研究进展

精神分裂症具有高致残率,治疗方法以抗精神病药物为主。体重增加是非典型抗精神病药(second generation antipsychotics,SGAs)的常见副作用,超重的精神分裂症患者罹患心血管疾病风险增高[1]。脂联素(adiponectin,APN)由脂肪细胞分泌,具有减轻体重、调控炎症、改善糖脂代谢等作用。众多研究发现,脂联素在抗精神病药导致体重增加中发挥重要作用[2],炎症、基因多态性、DNA甲基化、性激素等影响APN对体重增加的作用,但目前研究结论并不一致,其机制也尚不明确。本文对APN在抗精神病药导致体重增加中的作用进行综述,以求为降低精神分裂症患者肥胖风险、探索药源性肥胖的病理机制、早期预测体重增加及研究干预靶点提供理论参考。     

中国人群脂联素＋45位点基因单核苷酸多态性与缺血性脑卒中易感性的Meta分析

目的 通过Meta分析评估中国人脂联素基因＋45T＞G单核苷酸多态性（SNP）与缺血性脑卒中易感性的关系.方法 计算机检索Pubmed、Cochrane、中国期刊全文数据库（CNKI）及万方数据库中关于中国人群脂联素基因＋ 45T＞G SNP与缺血性脑卒中的相关性研究,对符合纳入标准的文献采用Rev Man5.2软件进行分析.结果 共纳入6篇文献,1604例患者.分析显示如下遗传模型中的差异明显,即等位基因模型（G VS.T）：OR=1.34,95％CI（1.04,2.72）;共显性模型（GG VS.TT）：OR=1.71,95％CI （1.27,2.30）;隐性模型（GG VS.F＋ TT）：OR=1.82,95％ CI（1.18,2.82）;显性模型（TG＋ GGVS.TT）：OR=1.22,95％CI （1.05,1.42）.结论 中国人群脂联素基因＋45T＞G SNP与缺血性脑卒中易感性相关,G等位基因可能为缺血性脑卒中的危险因素.     

脂联素与动脉粥样硬化关系的研究近况

研究发现,在脂肪组织分泌的多种脂肪因子中脂联素(脂联素)约占全部血清蛋白成分的0.01%,脂联素的生物活性与翻译后修饰密切相关[1]。脂联素具有多种重要的生理功能:(1)通过抑制血管细胞黏附分子(VCAM)及细胞间黏附分子(ICAM)在人类主动脉内皮细胞(HAECS)的表达,起到抗动脉粥样硬化的作用;(2)与肥胖者体重增减密切相关;(3)通过抑制巨噬细胞前体细胞的生长与抑制成熟巨噬细胞的功能调节炎症反应。脂联素(adiponeclin)分子结构理化特性及其相关调节因素1、脂联素分子结构及理化特征人类脂联素基因位于3p27[2]。脂联素(其mRNA长4.5kb)是一种特殊的胶原样因子,是由244个氨基酸组成的单肽。它没有跨膜疏水区,有胶原样结构域,分子间形成三聚体,进而又形成寡聚体的复合结构。其N端有1小段非胶原序列,其后是Gly-X-Pro或Gly-X-Y的重复序列(其含66个氨基酸)和芳香族氨基酸残基,C端有一球形结构域的片段(gAcrp30),长约27ku,其裂解位点位于第104个氨基酸上,gAcrp30活性远远大于脂联素,故推测脂联素是gAcrp30的无活性前体。2、脂联素调节因素(1)生长激素生长激素...     

高血压脑出血患者血浆超敏C反应蛋白及脂联素与apelin的相关性研究

目的探讨高血压脑出血患者血浆超敏C反应蛋白、脂联素和apelin之间的相关性。方法选择在徐州医学院附属医院门诊或神经外科住院的75例原发性高血压病患者，分为高血压组30例，高血压脑出血组45例；对照组为同期该院体检中心健康体健者，共40例。分别采用化学发光法和酶联免疫吸附法测定血浆超敏C反应蛋白、脂联素、apelin含量，并分析三者之间相关性。结果超敏C反应蛋白：高血压组显著高于对照组（P〈0．01），高血压脑出血组显著高于高血压组（P〈0．01）与对照组（P〈0．01）；脂联素：高血压组显著低于对照组（P〈0．01），高血压脑出血组显著低于高血压组（P〈0．01）与对照组（P〈0．01）；apelin：高血压组显著低于对照组（P〈0．01），高血压脑出血组显著低于高血压组（P〈0．01）与对照组（P〈0．01）。结论血浆超敏C反应蛋白、脂联素和apelin水平的变化与原发性高血压病情程度密切相关，可能对观察病情变化以及评估原发性高血压患者的预后具有重要的临床意义。     

药源性肥胖患者血清瘦素和脂联素水平检测

目的:探讨抗精神病药药源性肥胖患者血清瘦素和脂联素的水平及相关性.方法:选择21例药源性肥胖的住院患者(A组),20例首发精神分裂症患者(B组),20名健康体检人员作为对照组(C组),采用放射免疫法检测各组血清瘦素和脂联素水平,并分析各组血清瘦素及脂联素与体质量指数(BMI)相关性.结果:A组血清瘦素水平(13.3±8...     

人脂联素基因的克隆构建及其序列分析

背景：脂联素已经成为缺血性疾病基因治疗的新靶点,而成功进行脂联素基因治疗的关键是脂联素基因的克隆。基因克隆主要有定向克隆法和T-A克隆法,定向克隆法操作较复杂;而T-A克隆法操作简便,成功率高。 目的：应用T-A克隆法克隆人脂联素基因编码区,对其进行测序验证,并与GenBank比对。 设计、时间及地点：基因水平的验证实验,于2006-06/2008-12在福建医科大学附属第一医院高血压研究所及福建中医学院中西医结合研究院完成。 材料：脂肪组织取自福建医科大学第一附属医院外科患者术中切除的大网膜脂肪垫,液氮中冻存。Trizol为Invitrogen公司产品;M-MLV,Gel Extract Kit为PROMEGA公司产品;Taq酶为TIANGEN公司产品;限制性内切酶BamH Ⅰ,Sal Ⅰ,pMD18-T载体为TAKARA公司产品。 方法：从人大网膜脂肪组织提取总RNA,经反转录-聚合酶链反应扩增出人脂联素编码区基因,再将人脂联素基因编码区克隆入载体pMD18-T中,通过限制性内切酶酶切鉴定后,对其进行测序验证,并与GenBank比对。 主要观察指标：人脂联素克隆质粒酶切鉴定结果,人脂联素基因克隆序列与GenBank比对结果。 结果：扩增得到人脂联素基因编码区,获得人脂联素的正向和反向克隆,与GenBank中人脂联素基因编码区序列比对均为完全一致。 结论：成功地克隆出人脂联素基因编码区。     

Association of plasma retinol-binding protein-4, adiponectin, and high molecular weight adiponectin with metabolic adversities in patients with schizophrenia

Objective

Metabolic adversities are prevalent in patients with schizophrenia. Retinol-binding protein 4 (RBP4) and high molecular weight (HMW) adiponectin have been recently found to be associated with metabolic features in non-psychiatric population. The study aimed to evaluate the associations between metabolic features and RBP4, total adiponectin, and HMW adiponectin in patients with schizophrenia.

Methods

We recruited 109 patients with schizophrenia treated with clozapine or haloperidol and evaluated their body mass index (BMI), waist circumference, blood pressure, and fasting triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), fasting plasma glucose, insulin, RBP4, total adiponectin, and HMW adiponectin levels.

Results

We found that patients with metabolic syndrome (MS) had higher RBP4 level, and lower total adiponectin and HMW adiponectin levels than those without MS. There were no significant differences in metabolic features and adipocytokine levels between patients treated with clozapine and haloperidol. Most of the metabolic indexes were significantly correlated with the levels of adipocytokines. After adjusting the effects of age, gender, and BMI, marginal significant correlations existed between TG and RBP4 levels; HDL-C and total adiponectin and HMW adiponectin; insulin and HOMA-IR and HMW adiponectin. Receiver operating curve analysis showed that all of the three adipocytokines could differentiate patients with MS from those without MS. Meanwhile, total adiponectin and HMW adiponectin, but not RBP4, had the differentiating power for insulin resistance.

Conclusion

Higher RBP4 and lower total adiponectin and HMW adiponectin levels were observed in schizophrenic patients with MS. Only HMW adiponectin is marginally correlated with insulin sensitivity. The finding that metabolic profiles, but not the antipsychotic types, are associated with adipocytokine levels should be confirmed in longitudinal studies.     

Serum adiponectin and resistin levels in major depressive disorder

Lehto SM, Huotari A, Niskanen L, Tolmunen T, Koivumaa‐Honkanen H, Honkalampi K, Ruotsalainen H, Herzig K‐H, Viinamäki H, Hintikka J. Serum adiponectin and resistin levels in major depressive disorder. Objective: To examine the role of the adipose‐tissue‐derived low‐grade inflammation markers adiponectin and resistin in major depressive disorder (MDD) in a population‐based sample. Method: Serum levels of adiponectin and resistin were measured from 70 DSM‐IV MDD subjects and 70 healthy controls. Depression severity was assessed with the 29‐item Hamilton Depression Rating Scale. Results: The MDD group had lowered serum adiponectin levels. Regression modelling with adjustments for age, gender, overweight, several socioeconomic and lifestyle factors, coronary heart disease and metabolic syndrome showed that each 5.0 μg/ml decrease in serum adiponectin increased the likelihood of MDD by approximately 20% (P = 0.01). The resistin levels correlated with atypical (P = 0.02), but not with typical depressive symptoms (P = 0.12). Conclusion: Our findings suggest that the lowered adiponectin levels in MDD are depression‐specific and not explained by conventional low adiponectin‐related factors such as such as coronary heart disease and metabolic disorders.     

Decreased serum levels of adiponectin in subjects with autism

The neurobiological basis for autism remains poorly understood. We hypothesized that adipokines, such as adiponectin, may play a role in the pathophysiology of autism. In this study, we examined whether serum levels of adiponectin are altered in subjects with autism. We measured serum levels of adiponectin in male subjects with autism (n = 31) and age-matched healthy male subjects (n = 31). The serum levels of adiponectin in the subjects with autism were significantly lower than that of normal control subjects. The serum adiponectin levels in the subjects with autism were negatively correlated with their domain A scores in the Autism Diagnostic Interview—Revised, which reflects their impairments in social interaction. This study suggests that decreased levels of serum adiponectin might be implicated in the pathophysiology of autism.     

氯氮平与利培酮对血清脂联素的影响

目的：研究氯氮平与利培酮对血清脂联素（Adi）等代谢的影响。方法：69例精神分裂症患者随机分为氯氮平组和利培酮组。治疗6周测定患者血清Adi，血脂，空腹血糖、胰岛素水平，计算胰岛素抵抗指数（IR），测量身高、体质量，计算体质量指数（BMI），并与36名正常对照者比较。结果：两患者组治疗后的血清Adi明显降低，氯氮平组血清Adi改变与BMI相关；利培酮组血清Adi改变与IR和利培酮剂量相关。结论：氯氮平与利培酮治疗精神分裂症患者可引起血清Adi降低，并与体质量增加、IR、血脂及利培酮剂量密切相关。     

脂联素在脑梗死不同亚型病程中的变化规律研究

目的探讨不同分子量脂联素在脑梗死不同亚型病程中的变化及相关性。方法选取脑梗死患者182例为病例组。其中脑梗死亚型大动脉粥样硬化性卒中37. 36%,小动脉闭塞性卒中32. 41%,心源性脑栓塞30. 21%。选取来我院进行健康体检的115例非脑梗死患者作为对照组进行实验;观察不同分子量脂联素在不同TOAST分型病程分期中的变化;通过蛋白质免疫印迹检测不同分子量脂联素的表达量;通过酶联免疫吸附试验试剂盒法检测不同分子量脂联素在不同TOAST分型病程分期中的含量。结果冠心病史、糖尿病史、吸烟史和高血压史均与不同分子量脂联素在不同TOAST分型病程中的变化相关(P 0. 05),与对照组相比,脑梗死组中tAPN蛋白水平降低(P 0. 05);与对照组相比,在第1天、第4天、第10天、第15天,大动脉硬化组tAPN水平和HMW降低(P 0. 05),小动脉闭塞组tAPN水平和HMW降低(P 0. 05)。心源性脑栓组tAPN水平和HMW降低,HMW与tAPN密切相关(r=0. 999)。结论 tAPN、HMW与脑梗死密切相关,tAPN、HMW是比MMW和LMW更有效的脑梗死风险的生物标志物,有重要临床价值。     

慢性硬膜下血肿脂联素和基底膜蛋白多糖的表达

目的 探讨慢性硬膜下血肿脂联素（APN）、基底膜蛋白多糖（PL）的表达变化。方法 2019年5月至2020年5月钻孔引流术治疗CSDH共32例,所有病人入院后均服用阿托伐他汀钙片,直至复查CT示血肿完全吸收。术前、术后3 d、术后3周各取静脉血5 ml,术中采集血肿液5 ml,采用酶联免疫吸附法检测APN和PL的浓度。结果 血肿液APN浓度[（12.3±1.9）ng/ml]较外周血[（13.8±0.7）ng/ml]明显降低（P<0.05）,而PL浓度[（10.9±4.3）ng/ml]较外周血[（7.6±2.3）ng/ml]明显增高（P<0.05）。术后3 d外周血APN浓度[（14.1±0.7）ng/ml]较术前无明显变化（P>0.05）,术后3周外周血APN浓度[（15.3±0.8）ng/ml]较术前明显增高（P<0.05）。血肿液APN浓度与血肿液PL浓度呈明显负相关（r=-0.585,P<0.01）;血肿液APN浓度与血肿量呈明显负相关（r=-0.486,P<0.01）;血肿液PL浓度与血肿量呈明显正相关（r=0.557,P<0.01）。结论 本文结果提示APN和PL在CSDH发生、发展过程中具有一定作用,APN可作为CSDH阿托伐他汀治疗反应的评估指标。     

Plasma adiponectin elevation in elderly individuals with subsyndromal depression

Adiponectin, one of the adipokines, has believed to play a role in developing of depression, but the relationship between plasma adiponectin and depressive disorder is still unclear. To investigate the association between plasma adiponectin and depressive disorders, we measured plasma adiponectin concentrations in 785 randomly sampled elderly Koreans including 41 patients with major depressive disorder (MDD), 46 with minor depressive disorder (MnDD), and 61 with subsyndromal depression (SSD). Plasma adiponectin levels were different among the diagnostic groups (df=3, F=4.928, P=0.002). The plasma adiponectin level in the SSD patients was higher than in the non-depressed controls (NC) (12.48 ± 8.38 μg/ml versus 9.27 ± 6.21 μg/ml, P=0.001, Tukey's post hoc comparison). However, plasma adiponectin levels in the MnDD and MDD patients were comparable with those found in the NC (P>0.1, Tukey's post hoc comparison). The elevation of plasma adiponectin in the SSD patients remained significant in men (P=0.002, Tukey's post hoc comparison) but not in women. In the subjects without MDD and MnDD, plasma adiponectin level was positively correlated with the Hamilton Depression Rating Scale score (r=0.156, P<0.001) and the Geriatric Depression Scale (r=0.117, P=0.002). When men and women were analyzed separately, these significant correlations were confined to men. Circulating adiponectin concentration may play a role in compensation on process for depressive mood.