P53结合位点对人 NOD8 基因的调控

目的:探讨P53结合位点在NOD8基因调控中的作用。方法:利用生物信息学方法,我们发现人与黑猩猩的NOD8基因核心启动子区域相似位置含有P53结合位点;以人基因组DNA为模板,PCR扩增含有人NOD8基因序列,构建含有/缺失人P53结合位点的NOD8基因启动子驱动的、表达绿色荧光蛋白-NOD8融合蛋白的质粒pNOD8(760bp)-EGFP-NOD8和mpNOD8(750bp)-EGFP-NOD8;将构建的重组质粒经阳离子聚合物JetPeiTM介导瞬时转染HEK293细胞中,并加入不同浓度的P53抑制剂pifithrinalpha(PFT-α)处理HEK293细胞,用RT-PCR和Westrenblotting方法检测NOD8mRNA和蛋白的表达;此外,用pNOD8(760bp)-EGFP质粒转染HEK293细胞,利用染色质免疫共沉淀法(ChIP)观察P53是否与NOD8启动子结合。结果:经酶切鉴定和序列测定证实重组质粒构建成功。ChIP实验证实P53能与NOD8启动子结合。pNOD8(760bp)-EGFP-NOD8转染组中NOD8mRNA的表达显著高于pEGFP-C2转染组(P＜0.05),并且NOD8mRNA在缺失人P53结合位点的mpNOD8(750bp)-EGFP-NOD8转染组中的表达明显降低(P＜0.01);同时发现加入PFT-α的pNOD8(760bp)-EGFP-NOD8转染组NOD8mRNA的表达显著下降,并呈剂量依赖关系,其中90μmol/LPFT-α对NOD8mRNA表达的抑制作用最为显著(P＜0.01)。与mRNA检测结果一致的是pNOD8(760bp)-EGFP-NOD8转染组NOD8蛋白的表达量显著高于对照组pEGFP-C2;而mpNOD8(750bp)-EGFP-NOD8转染组NOD8蛋白的表达量明显低于pNOD8(760bp)-EGFP-NOD8转染组和加入PFT-α的pNOD8(760bp)-EGFP-NOD8转染组(P＜0.01)。结论:P53结合位点在NOD8基因调控中起着重要的作用,并且P53结合位点与NOD8基因之间可能存在正反馈调节。     

ABCG2基因rs2231142位点多态性与浙南地区人群原发性痛风的关系

目的探讨三磷酸腺苷结合盒转运蛋白G2基因(ABCG2)rs2231142位点与浙南地区原发性痛风的相关性。方法收集浙南地区原发性痛风样本508例和正常健康体检样本558例,用微滴式数字化PCR技术进行基因分型,分析该位点多态性与痛风的相关性。结果痛风组尿酸、三酰甘油、胆固醇、尿素氮、肌酐以及收缩压水平显著高于正常组(P0.05)。痛风组ABCG2基因rs2231142位点AA型和A等位基因频率显著高于正常组(P0.05)。痛风组AA基因型/AC基因型尿酸、尿素氮和肌酐水平型显著高于痛风组CC基因(P0.05)。结论 ABCG2基因rs2231142位点是浙南地区原发性痛风的易感基因位点,提示A等位基因提高了痛风患者的尿酸水平,携带AA基因型的个体更易患痛风。     

脂代谢相关基因多态性与缺血性脑卒中

<正>脑卒中是指各种原因所致脑部血液供应障碍,导致脑组织缺血、缺氧性坏死,出现相应神经功能缺损的一类疾病,其中约80%为缺血性脑卒中(Ischemic Stroke,IS),是目前造成患者死亡和神经功能残疾的主要原因。IS的病因及发病机制极其复杂,对IS孪生子和家系的遗传学研究得到的证据表明,遗传因素在IS发病中起重要作用。动脉粥样硬化(Atherosclerosis,AS)是IS发病的主要病理学基础,而AS与脂类代谢异常密切相关。因此,脂代谢通路相关基因突变     

血清PCSK9与妊娠期糖尿病患者糖脂代谢以及胰岛素抵抗的相关性研究

目的 分析血清前蛋白转化酶枯草溶菌素9(PCSK9)与妊娠期糖尿病(GDM)患者糖脂代谢以及胰岛素抵抗(IR)的关系.方法 选取我院在2019年3月至2020年6月期间收治的GDM患者86例作为研究组,另选取同期在我院进行产检的健康孕妇40例作为对照组.分析血清PCSK9在所有研究对象中的表达情况,分析GDM患者血清P...     

个体化孕期营养指导对妊娠期糖尿病患者糖脂代谢及脂肪因子的影响

目的 观察个体化孕期营养指导对妊娠期糖尿病患者糖脂代谢及脂肪因子的影响。方法 选取2022年1月-2023年1月我院收治的76例妊娠期糖尿病患者为研究对象,采用随机数字表法分为对照组和观察组,各38例。对照组给予常规饮食指导及正常产检,观察组在此基础上给予个体化孕期营养指导。比较两组血糖指标、血脂指标[总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）]、孕期并发症、妊娠结局及焦虑和抑郁评分。结果 两组空腹血糖、糖化血红蛋白、餐后2 h血糖均低于治疗前,且观察组低于对照组（P＜0.05）;两组TC、TG、LDL-C、HDL-C均低于治疗前,且观察组低于对照组（P＜0.05）;观察组孕期并发症发生率（10.53%）低于对照组（21.05%）（P＜0.05）;观察组不良妊娠结局发生率为13.16%,低于对照组的28.95%（P＜0.05）;两组焦虑、抑郁评分低于治疗前,且观察组低于对照组（P＜0.05）。结论 个体化孕期营养指导治疗对妊娠期糖尿病患者糖脂代谢及脂肪因子具有积极的促进作用,可降低其妊娠期并发症,改善妊娠结局和不良心理,具有较理想的效果。     

ABCG2 基因rs3114018单核苷酸多态性与武陵山地区痛风及高尿酸血症的相关性研究

目的：探讨三磷酸腺苷结合盒转运蛋白 G2 基因(ABCG2) rs3114018位点与武陵山地区原发性痛风和高尿酸血症的相关性。方法：采用Hi-SNP结合多重PCR技术和高通量测序技术,对159例原发性痛风患者、188例高尿酸血症患者和106例健康对照者的ABCG2 rs3114018位点进行基因分型,并分析不同等位基因或基因型与原发性痛风、高尿酸血症易感性的关系。结果：痛风组基因型频率与正常组相比差异具有统计学显著统计学意义（P<0.001),Logistic回归分析显示,基因型CC和C等位基因均是痛风的易感因素(OR=5.861,95%CI:2.239~15.340,P<0.001;OR=2.461,95%CI:1.671~3.622,P<0.001）;高尿酸血症组基因型频率与正常组相比没有显著差异（P>0.05),该位点多态与高尿酸血症没有相关性（P>0.05）;痛风组与高尿酸血症组相比,基因型频率具有统计学差异（P<0.001),基因型CC和C等位基因分别使痛风的发生风险增加了4.131倍和1.994倍。结论：ABCG2 rs3114018位点单核苷酸多态性可能与武陵山地区原发性痛风的发病相关,等位基因C可能是原发性痛风发病的危险因素,携带CC基因型的个体可能更容易患痛风;该位点多态性与高尿酸血症没有显著相关性。     

内皮型一氧化氮合酶基因第7外显子894位点多态性与妊娠期高血压疾病

目的探讨内皮型一氧化氮合酶基因(endothelia n itric oxide synthase,eNOS)第7外显子894位点多态性现象与妊娠期高血压疾病(hypertensive d isorder comp licating pregnancy)的相关性及其在发病机制中的作用。方法应用聚合酶链反应-限制性片段长度多态性技术检测妊娠期高血压疾病患者和健康孕妇的eNOS基因第7外显子894位点多态性。对两组之间的基因型和等位基因频率进行比较。采用W estern b lot方法分别检测胎盘中eNOS蛋白含量在正常组和病例组之间、病例组中两种基因型之间是否存在表达水平的差异。结果T等位基因频率在正常孕妇组为6.87%,妊娠期高血压疾病组为23.00%(χ2=14.01,P=0.001,OR=4.05 95%可信区间为1.88~8.74),TG TT基因型频率在两组分别为13.75%和36.00%,χ2=8.79,P=0.003;OR=3.53 95%可信区间为1.49~8.33)差异有统计学意义。病例组中eNOS蛋白表达低于正常组,病例组中GG基因型组表达水平高于TG TT组(P<0.01)。结论eNOS基因第7外显子894位点多态性与妊娠期高血压疾病具有相关性,该位点的突变可引起eNOS蛋白表达降低,是引起妊娠期高血压疾病的可能机制。     

5-羟色胺转运体基因多态性与焦虑相关人格特质

5-羟色胺转运体（5-HTT）基因是个体间人格遗传差异和易发生多种精神障碍的一个最有前景的候选基因。该基因多态性通过影响基因转录而影响其功能,参与焦虑相关人格特质的调节。本文就 5-HTT基因与焦虑相关人格特质的关系及其研究进展作一综述。     

HLA-Ⅱ类基因多态性与妊娠期糖尿病的关系

妊娠期糖尿病是遗传因素和环境因素共同作用的结果，而人类白细胞抗原（HLA）是其最重要的影响因素之一，多种研究结果表明妊娠期糖尿病的结局可能与其他糖尿病有关联，不同国家不同地区人群各型糖尿病的人类白细胞抗原基因型不同，现就此综述如下。     

First case of sitosterolemia caused by double heterozygous mutations in ABCG5 and ABCG8 genes

We present the first case of sitosterolemia caused by double heterozygous mutations in adenosine triphosphate-binding cassette subfamily G members 5 and 8 (ABCG5 and ABCG8) genes. A 1-year-old girl was admitted to Kanazawa University Hospital due to her hyper low-density lipoprotein (LDL)-cholesterolemia (453 mg/dL) as well as intertriginous xanthomas associated with breastfeeding. Initially, she was suspected as familial hypercholesterolemia (FH). However, her LDL cholesterol level significantly reduced after her weaning from breastfeeding. In addition, cascade screening did not show any evidence supporting dominant inheritance pattern as FH. Genetic analyses were performed using custom panel focusing on exome regions of 21 lipid-associated genes, including FH-causing genes (LDL receptor, proprotein convertase subtilisin/kexin type 9, apolipoprotein B), and ABCG5 and ABCG8 genes. In addition to a single deleterious mutation in ABCG5 gene (NM_022436.2:c.1166G>A or NP_071881.1:p.Arg389His), single deleterious mutation in ABCG8 gene (NM_022437.2:c.1285A>C or NP_071882.1:p.Met429Leu) was also identified. Segregations of those mutations from her parents were confirmed. Her serum sitosterol level was significantly elevated to 15.9 μg/mL, leading to her definite diagnosis as sitosterolemia. The ABCG5 and ABCG8 proteins form heterodimers and act as a complex. To the best of our knowledge, this is the first case exhibiting sitosterolemia caused by both ABCG5 and ABCG8 gene mutations.     

PPARγ在脂肪细胞分化和糖脂代谢中的作用

肥胖症和代谢综合征已经成为危害人类健康的重要问题。过氧化物酶体增殖物激活受体(PPARs)是一类配体激活转录因子，属于细胞核激素受体超家族。PPARs的3种亚型在调节糖脂代谢中扮演关键的角色。其中，过氧化物酶体增殖物活化受体γ(PPARγ)是脂肪细胞基因表达和胰岛素细胞间信号传递的主要调节者。     

mTOR介导转录因子调控细胞糖脂代谢的研究进展

哺乳动物雷帕霉素靶蛋白(mTOR)是一种重要的信号分子,参与体内蛋白质合成,细胞增殖、细胞周期、能量代谢和自噬等过程.mTOR的失活可导致肿瘤和代谢性疾病的发生.其中,HIF1α、c-Myc、FoxO1、SREBPs、PPARγ/PPARα及TFEB作为mTOR的下游信号,与细胞的糖脂代谢密切相关.     

The impact of daily work load during pregnancy on lipid metabolism in the liver of the offspring

Summary Changes of selected indicators of lipid metabolism in the liver of the offspring of rat mothers exercised during pregnancy and of control mothers were followed up. Male offspring of exercised mothers were heavier at the age of 35 days and lighter at the age of 90, 100, and 108 days. The concentration of total lipids and fatty acids was raised in female offspring at the age of 35 and 90 days, and did not differ or was reverse (i.e., lower) in male offspring of exercised mothers compared to controls. The cholesterol concentration in the liver was increased in both female and male offspring of exercised mothers. The liposynthesis (studied in vivo after injection of Na-acetate-1-¹⁴C) tended to be lower in female offspring, and varied in male offspring of exercised mothers. In a subsequent in vitro study (incubation of liver slices with Na-acetate-1-¹⁴C) a lower total lipid and fatty acid concentration in the liver of male offspring of exercised mothers (108 days old) was found together with higher level of serum free fatty acids and unchanged liposynthesis. Finally, a higher concentration of cholesterol, higher synthesis of fatty acids and lower cholesterogenesis in small intestine in male offspring of exercised mothers 100 days old compared to those of control mothers was shown. As follows, daily work load during pregnancy results in significant changes of lipid metabolism in the liver and small intestine of the offspring.     

Association detection between genetic variants in the microRNA binding sites of toll-like receptors signaling pathway genes and bladder cancer susceptibility

Bladder cancer (BCa) is the second most common urological malignancy, and the incidence of BCa has dramatically increased recently. Various toll-like receptors (TLRs) signaling pathway proteins were proven to be associated with BCa susceptibility. However, the effect of genetic variants in TLRs signaling pathway genes on risk of BCa has not been elucidated clearly. Previous studies mainly focused on the coding region of target genes, while in this study, polymorphisms in the non-coding region, microRNA (miRNA) binding sites were investigated as potential targets. We used bioinformatics approach to screen 100 BCa related TLRs signaling pathway genes. Candidate polymorphisms were select in this region and 8 polymorphisms were confirmed. Rs72552316, located at the 3’UTR of the TLR7 gene, exhibited significant association with risk of BCa, indicating a strong relationship with decreased risk of BCa (P ≤ 0.0001). Furthermore, no association was detected between all the polymorphisms and recurrence-free survival time of overall study population or non-muscle invasive BCa subgroups. In conclusion, rs72552316 in the miRNA binding sites of TLR7 might contribute to BCa susceptibility, and this finding provided new targets for high BCa risk population screening.     

Lack of downstream insulin-mimetic effects of visfatin/eNAMPT on glucose and fatty acid metabolism in skeletal muscles

Aim: Recent studies regarding downstream effects of visfatin/eNAMPT in skeletal muscles have attracted much attention as the previous reports suggested this adipokine may exert insulin‐mimetic effects. However, studies in vivo present conflicting data and are still controversial. In this present work, we sought to investigate whether visfatin/eNAMPT is able to reproduce insulin effects on glucose transport and lipid metabolism. Methods: We have used isolated skeletal muscles with different fibre type composition (Soleus and EDL) to examine glucose transport, GLUT‐4 translocation, phosphorylation of insulin signalling pathway proteins, as well as the key parameters for fatty acid metabolism. Results: We found that, in vitro exposure to visfatin/eNAMPT increased skeletal muscle glucose transport but only in EDL (+20%) and not in Soleus muscle (+5%). Interestingly, classical insulin signalling pathways were not significantly involved in this process. Concomitantly, visfatin/eNAMPT exerted no significant effects on muscle’s fatty acids (FA) metabolism as no change in either palmitate oxidation or esterification was observed. Importantly, combined insulin and visfatin effects were not found, suggesting non‐additivity. Conclusion: Our data suggest that visfatin/eNAMPT plays a rather limited role in regulating skeletal muscle glucose transport and FA metabolism.     

Effect of phenformin on lipid and carbohydrate metabolism in pregnant rats

A decrease in the blood levels of cholestrol, phospholipids, and free fatty acids was observed in rats receiving the biguanide phenformin (5–25 mg daily by mouth) from the first to eighth day of pregnancy, but no developmental anomalies of the fetuses or placenta were found. The acceptability of biguanide administration during pregnancy is discussed.Presented by Academician of the Academy of Medical Sciences of the USSR A. I. Serebrov.Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 82, No. 7, pp. 825–827, July, 1976.     

Effects of adrenaline on lactate, glucose, lipid and protein metabolism in the placebo controlled bilaterally perfused human leg

Aim: Adrenaline has widespread metabolic actions, including stimulation of lipolysis and induction of insulin resistance and hyperlactatemia. Systemic adrenaline administration, however, generates a very complex hormonal and metabolic scenario. No studies employing regional, placebo controlled and adrenaline infusion exist. Our study was designed to test the hypothesis that local placebo controlled leg perfusion with adrenaline directly increases local lactate release, stimulates lipolysis, induces insulin resistance and leaves protein metabolism unaffected. Methods: We studied seven healthy volunteers with bilateral femoral vein and artery catheters during 3‐h basal and 3‐h hyperinsulinemic (0.6 mU kg^?1 min^?1) euglycemic clamp conditions. One femoral artery was perfused with saline and the other with adrenaline (0.4 μg min m^?2). Lipid metabolism was quantified with [9,10‐³H] palmitate and amino acid metabolism with ¹⁵N‐phenylalanine and lactate and glucose by raw arterio‐venous differences. Results: Femoral vein plasma adrenaline increased ≈eightfold in the perfused leg with unaltered blood flows. Adrenaline perfusion significantly increased local leg lactate release from 0.01 to 0.25 mmol min^?1 per leg, palmitate release in the basal state 11.5–16.9 μmol min^?1 per leg and during the clamp 2.62–8.44 μmol min^?1 per leg. Glucose uptake decreased during the clamp from ≈180 to 30 μmol min^?1 per leg. Phenylalanine kinetics was not affected by adrenaline. Conclusion: Adrenaline directly increases lactate release and lipolysis and inhibits insulin‐stimulated glucose uptake in the perfused human leg. Adrenaline has no direct effects on peripheral amino acid metabolism. Adrenaline‐induced lactate release from striated muscle may be an important mechanism underlying hyperlactatemia in the critically ill.     

妊娠期糖尿病孕妇血清视黄醇结合蛋白4水平与糖脂代谢相关性的初步研究

目的了解妊娠期糖尿病孕妇血清视黄醇结合蛋白4（RBP4）水平与糖脂代谢的关系。方法采用酶联免疫吸附试验（ELISA）测定50例孕晚期妊娠期糖尿病孕妇及50例正常孕晚期孕妇血清RBP4水平;同时测定两组孕妇空腹血糖（FPG）、糖化血红蛋白（HbAlC）、血清总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白（HDL—C）、低密度脂蛋白（LDL—C）、栽脂蛋白A—I（ApoA-1）、载脂蛋白B（ApoB）水平。结果（1）妊娠期糖尿病组孕妇血清RBP4水平为（18．48±4．6）ng／ml,明显高于正常孕妇血清RBP4水平（13．26±2．35）ng／ml,差异有统计学意义（P〈0．01）。（2）妊娠期糖尿病组孕妇FPG、HbAlCs水平分别为（5．40±0．57）mmol／L、（5．68±0．58）％,明显高于正常孕妇血清水平（4．99±0．27）mmol／L、（4．75±0．51）％,差异有统计学意义（P〈0．01）。（3）妊娠期糖尿病组孕妇血清TC、TG、ApoB、分别为（5．70±0．88）mmol/L、（3．17±1．06）mmol／L、（0．3l±0．13）异／L,明显高于正常孕妇血清水平（5．25±0．75）mmol／L、（1．26±0．31）mmol／L、（0．20±0．09）∥L,差异有统计学意义（P〈0．01或P〈0．05）;妊娠期糖尿病组孕妇血清ApoA—Ⅰ水平为（2．12±0．30）g／L,明显低于正常孕妇血清水平（2．62±0．70）g／L,差异有统计学意义（P〈0．01）;妊娠期糖尿病组孕妇血清LDL—C血清水平为（3．51±0．75）mmol／L,高于正常孕妇血清水平（3．16±0．76）mmol／L,但差异无统计学意义（P〉0．05）。（4）Pearson相关分析结果显示,两组孕妇血清RBP4水平分别与TG、HbAlC呈显著正相关性（r=0．27,0．39,P〈0．05,P〈0．01）;与FPG、TC、HDL—C、LDL—C、ApoA-1、ApoB、孕晚期体质指数（bodymassindex,BMO无明显相关性（r=,0．063,0．075,0．127,0．046,－0．159,0．085,－0．3,P〉0．05）。结论妊娠期糖尿病孕妇糖脂代谢紊乱,血清RBP4水平明显升高,RBP4可能参与了妊娠期糖尿病孕妇糖脂代谢紊乱机制。     

Effect of the antioxidant emoxypine on lipid metabolism in the lungs during development of pulmonary edema

Department of Pathophysiology, Yaroslavl' State Medical Institute. All-Union Research Center for Safety of Biologically Active Substances, Kupavna, Moscow Region. (Presented by Academician of the Academy of Medical Sciences of the USSR A. G. Chuchalin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 113, No. 2, pp. 139–141, February, 1992.