高能量膳食对中老年食蟹猴糖尿病相关基因表达的影响

本研究选择空腹血糖值(FPG)在正常范围内(3.20 mmol/L≤FPG<5.50 mmol/L)的中老年食蟹猴(Macaca fascicularis)60只,高能量膳食诱导12个月后,将其分为正常血糖组和诱高血糖组(FPG≥5.50 mmol/L)。采用荧光定量PCR技术对2组中36个糖尿病相关基因在诱导前后外周血白细胞中的mRNA表达量进行分析。结果表明,高能量膳食诱导后,诱高血糖组FPG和甘油三酯(TG)显著高于正常血糖组(P<0.05),而胆固醇(TCHO)、高密度脂蛋白(HDL-C)、低密度脂蛋白(LDL-C)与分组无显著相关性(P>0.05)。基因表达水平上,诱高血糖组和正常血糖组均有血管紧张素转换酶基因(ACE)、肝糖原磷酸化酶基因(PYGL)、水通道蛋白基因(AQP2)等19个基因的mRNA表达量在高能量膳食诱导前后存在显著差异(P<0.05),且基因的表达模式变化一致,但诱高血糖组的mRNA表达量变化大,且三磷酸腺苷柠檬酸裂解酶(ACLY)、选择素L(SELL)、突触相关蛋白23(SNAP23)、突触融合蛋白(STX4)这4个基因的mRNA表达水平仅在诱高血糖组高能量膳食诱导前后呈差异表达(P<0.05)。     

肥胖2型糖尿病患者神经肽Y水平与糖脂代谢的相关性分析

目的:探讨肥胖2型糖尿病患者神经肽Y(NPY)水平与糖脂代谢的相关性。方法:选择2017年7月至2019年7月我院接诊的134例肥胖2型糖尿病患者为本研究对象,设为观察组,并选择我院收治的2型糖尿病非肥胖患者100例作为对照组,分析腰围、腹围、臀围、BMI、腰臀比(WHR)、血清NPY、空腹血糖(FPG)、糖化血红蛋白(Hb Alc)、空腹胰岛素(FINS)、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)水平变化情况,及其之间的相关性分析。结果:观察组腹围、腰围、臀围、腰臀比及BMI水平均显著高于对照组,差异显著(P0.05);观察组患者血清NPY、FPG、Hb Alc水平显著高于对照组,FINS水平显著低于对照组,差异显著(P0.05);观察组患者血清TC、TG、LDL-C水平显著高于对照组,HDL-C水平显著低于对照组,差异显著(P0.05);将FPG、Hb Alc、FINS、TC、TG、LDL-C、HDL-C作为因变量,将血清NPY作为自变量,在相关性分析结果中显示,血清NPY和FPG、Hb Alc、TC、TG、LDL-C之间均呈正相关(r=0.399,0.173,0.435,0.451,0.376,P均0.05),血清NPY和FINS、HDL-C之间均呈负相关(r=-0.566,-0.223,P均0.05)。结论:在肥胖2型糖尿病患者中NPY水平显著升高,且与腹部脂肪增加、糖脂代谢显著相关。     

2型糖尿病相关基因在人和食蟹猴外周血白细胞中的表达模式

2型糖尿病(T2DM)是一种多因素相关的复杂的代谢性疾病。采用实时PCR技术了解51个T2DM相关基因mRNA在健康和糖尿病人/食蟹猴外周血白细胞中的表达模式。结果表明,与健康组相比,糖尿病猴中有34个基因表达量差异显著(P<0.05),约为66.7%,其中24个基因表达上调(P<0.05);而糖尿病人中有26个基因表达量差异显著(P<0.05),约为50.1%,其中16个基因表达上调(P<0.05),这些基因表达受到糖代谢、脂肪代谢、炎症等方面的影响。糖尿病人与食蟹猴样本中有18个基因都存在差异性表达(P<0.05),表达模式基本一致。因此,食蟹猴可以作为研究糖尿病的较理想的模式动物,外周血白细胞基因的表达模式可以为糖尿病早期诊断和预后评价提供重要指标。     

食蟹猴心血管病风险因素与心血管病相关基因在外周血白细胞表达的相关性

研究心血管病风险因素和心血管病相关基因表达的相关性有助于心血管病风险预警和早期诊断研究。该文采用温和的动脉粥样硬化膳食(0.053mg胆固醇/千焦、40%的能量来源于脂肪)喂养中老年雄性食蟹猴(Macaca fascicularis)(12个月),根据传统心血管病风险因素筛选低、高风险食蟹猴,然后采用荧光定量PCR技术检测113个心血管病相关基因在正常组、低风险和高风险组食蟹猴外周血白细胞内的表达差异。结果在食蟹猴外周血白细胞中共检测到65个心血管病相关基因,其中低、高风险组有16个基因相对于正常组表达上调(P<0.05),19个基因表达下调(P<0.05),另外,还有15个基因表达模式特异(P<0.05)。此外,还检测到42个心血管病相关基因在人和食蟹猴外周血白细胞内均有效表达,其中22个基因在两者之间表达模式一致。上述结果为进一步研究心血管病风险预警和早期诊断指标,缩小了基因遴选范围。     

自发性与膳食诱发性食蟹猴2型糖尿病其相关基因的表达比较

采用荧光定量PCR技术对自发性和膳食诱发性T2DM食蟹猴外周血白细胞中36个糖尿病相关基因的表达水平进行分析。在36个基因中,糖尿病组的G6PC、CCR2B、CTLA4等19个基因的表达量与对照组相比存在显著差异(P<0.05),且这些基因在诱发组和自发组中的表达模式基本一致。36个基因中,诱发组基因的表达量普遍高于自发组,但大部分基因表达量在两组中差异不显著,表明诱发性和自发性食蟹猴T2DM模型均可作为糖尿病研究较理想的动物模型。因此,通过高能量膳食诱导的食蟹猴糖尿病模型可以替代自发的糖尿病猴,且基因表达量的变化可为疾病的诊断和治疗提供帮助。     

血清Fractalkine、Apelin水平与糖尿病视网膜病变患者血糖、血脂以及病程的关系研究

目的:研究血清Fractalkine(FKN)、爱帕琳肽(Apelin)水平与糖尿病视网膜病变(DR)患者血糖、血脂以及病程的关系。方法:选取我院于2015年1月至2016年12月收治的160例糖尿病患者为研究对象,行眼底荧光造影、裂隙灯显微镜检查,按照检查结果将其区分为非增生型DR组(稳定组,43例)、背景期DR组(背景组,62例)和增殖期DR组(增殖组,55例),另外于同期选取我院40例健康体检者为健康对照组(健康组),测量4组血清FKN、Apelin、空腹血糖(FPG)、餐后2h血糖(2hPG)、糖化血红蛋白(HbA1c)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、甘油三酯(TG)和总胆固醇(TC)水平,使用Pearson相关性分析分析血清FKN、Apelin与FPG、2hPG、HbA1c、HDL-C、LDL-C、TG、TC、糖尿病病程的相关性。结果:血清FKN、Apelin水平比较:增殖组背景组稳定组健康组,各组间比较差异具有统计学意义(P0.05);血清FPG、2hPG、HbA1c、LDL-C、TG、TC水平比较:增殖组背景组稳定组健康组,各组间比较差异具有统计学意义(P0.05);血清HDL-C水平比较:健康组稳定组背景组增殖组,各组间比较差异具有统计学意义(P0.05);采用Pearson相关性分析显示,血清FKN水平与FPG、2hPG、HbA1c、LDL-C、TG、TC、糖尿病病程呈正相关性(r=0.321、0.215、0.645、0.154、0.215、0.325、0.578,P0.05),与HDL-C呈负相关性(r=-0.547,P0.05);血清Apelin水平与FPG、2hPG、HbA1c、LDL-C、TG、TC、糖尿病病程呈正相关性(r=0.245、0.574、0.951、0.357、0.357、0.159、0.546,P0.05),与HDL-C呈负相关性(r=-0.459,P0.05);糖尿病病程、HbA1c、LDL-C、HDL-C、FKN和Apelin为DR病程的相关影响因素。结论:糖尿病伴发DR患者血清FKN、Apelin水平随着病程的加重逐渐增加,且这两种因子的水平与患者血糖、血脂代谢关系密切。     

高脂血症恒河猴血清RETN与血脂的相关性分析

目的探讨高脂血症恒河猴血清抵抗素（RETN）水平与血脂的相关性。方法高脂血症恒河猴和健康恒河猴各8只,分别为实验组及对照组,测定其空腹血清RETN、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）,分析高脂血症恒河猴血清RETN水平与血脂的关系。结果实验组的血清RETN水平、TC、LDL-C显著高于对照组（P〈0.05）,实验组TG较对照组显著降低（P〈0.05）;两组HDL-C差异不显著（P〉0.05）。相关分析显示,血清RETN与TC、LDL-C正相关,与TG负相关,与HDL-C无相关性。结论高脂血症恒河猴血清RETN水平与血脂存在相关性,可为人类高脂血症研究提供实验数据。     

9758 例健康体检者血糖与血脂的关系分析

目的:探讨健康体检人群血糖与血脂现况及两者之间的相关性。方法:采集我院9758例健康体检者的空腹静脉血,检测其空腹血糖(FPG)、总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白(HDL-C)和低密度脂蛋白(LDL-C)水平,比较不同FPG水平组间各血脂水平,分析FPG水平与血脂的相关性。结果:各年龄组FPG、TC、TG、HDL-C和LDL-C水平差异均具有统计学意义(P0.05);FPG均与TC、TG和LDL-C水平呈现正相关(r=0.127,0.189,0.141,P0.005),而与HDL-C呈现负相关(r=-0.112,P0.005);根据FPG水平由高到低分为糖尿病(DM)组,血糖调节受损(IFG)组及血糖正常组,其中对TC和LDL-C水平异常率而言,IFG组DM组血糖正常组;对TG、HDL-C水平异常率而言,DM组IFG组血糖正常组。结论:健康人群中血糖和血脂水平呈现一定的相关性,两者的水平异常会增加慢性疾病的发生风险。     

子痫前期患者血清APN、TNF-α、Apelin水平的表达及相关性研究

目的:探讨子痫前期患者血清脂联素(APN)、肿瘤坏死因子-α(TNF-α)、Apelin水平的表达及相关性。方法:选取2015年10月到2017年8月在辽河油田总医院妇产科就诊的子痫前期患者86例,根据患者的病情严重程度将其分为轻度子痫前期组(46例)和重度子痫前期组(40例),另选取同期在我院进行产检的健康孕妇40例作为对照组,比较三组受试者血清中APN、TNF-α、Apelin、低密度脂蛋白胆固醇(LDL-C)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)和总胆固醇(TC)水平,并分析子痫前期患者血清中APN、TNF-α、Apelin、LDL-C、TG、HDL-C、TC的相关性。结果:重度子痫前期组血清中APN水平低于轻度子痫前期组和对照组,TNF-α、Apelin水平高于轻度子痫前期组和对照组(P0.05);轻度子痫前期组血清中APN水平低于对照组,TNF-α、Apelin水平高于对照组(P0.05)。重度子痫前期组血清中LDL-C、TG、TC水平高于轻度子痫前期组和对照组,HDL-C水平低于轻度子痫前期组和对照组(P0.05);轻度子痫前期组LDL-C、TC水平高于对照组,HDL-C水平低于对照组(P0.05)。Pearson相关性分析结果显示,子痫前期患者血清中APN与TNF-α、Apelin、LDL-C、TG呈负相关,与HDL-C呈正相关(P0.05);TNF-α与Apelin、LDL-C、TG、TC呈正相关,与HDL-C呈负相关(P0.05);Apelin与LDL-C、TG、TC呈正相关,与HDL-C呈负相关(P0.05)。结论:子痫前期患者血清中APN水平明显下降,TNF-α、Apelin明显升高,三种指标可相互影响,且均可影响机体的脂质代谢水平,共同调节子痫前期患者的疾病进展。     

吸烟对小鼠血清介导巨噬细胞胆固醇流出的影响及其机制

目的:探讨吸烟对小鼠血清介导巨噬细胞胆固醇流出的影响及其机制.方法:14只C57BL/6小鼠随机分为对照组和吸烟组.吸烟组小鼠被动吸烟8周后,检测血清总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、甘油三酯(TG)和丙二醛(MDA)浓度.采用液体闪烁计数法分别检测对照组小鼠血清、吸烟组小鼠血清、吸烟组小鼠血清+N-乙酰半胱氨酸(NAC,2mM)介导的细胞胆固醇流出效率.结果:与对照组相比,吸烟组小鼠血清中HDL-C显著降低,TG显著升高,TC和LDL-C无显著差别,并且吸烟组小鼠血清中MDA水平也显著升高.吸烟组小鼠血清介导巨噬细胞胆固醇流出效率明显降低,给予抗氧化剂NAC共同孵育可以显著增加吸烟组小鼠血清胆固醇流出效率.结论:吸烟显著降低小鼠血清介导的巨噬细胞胆固醇流出效率,其机制可能与吸烟降低HDL-C水平以及促进HDL脂质过氧化有关.     

2011~2014 年体检者血压水平与血清尿酸水平的关系

目的：分析2011~2014 年我院体检者血压水平与血清尿酸(UA)水平的关系。方法：选择我院2011~2014 年2150 例体检者为 研究对象,均完成血压（SBP、DBP),心率（HR）、身高、体重指数（BMI）、空腹血糖（FPG）、高密度脂蛋白胆固醇(HDL-C) 、低密度脂 蛋白胆固醇(LDL-C) 、血清总胆固醇(TC) 、甘油三酯(TG)及UA 指标检测,并对检测结果进行分析。结果：2150 例体检人群中,高 血压为860 人,占40.0%,高血压组BMI、FPG、LDL-C、TC、TG 及UA 均明显高于非高血压组,而HDL-C 明显低于非高血压组, 比较差异具有统计学意义（P＜0.05）;多因素Logistic 回归分析显示,上述指标均为高血压的独立危险因素（P＜0.05）。结论：血压 水平的升高与UA水平具有密切联系,早期控制UA水平对预防高血压的发生具有重要意义。     

健身气功八段锦对肥胖中年女性糖尿病患者相关指标的影响

目的：了解健身气功八段锦对肥胖中年女性糖尿病患者相关指标的影响,为糖尿病的干预治疗方案提供新的思路。方法：以40名中年女性肥胖糖尿病患者作为研究对象,年龄57.2±5.4岁,随机分为对照组和练功组（n=20）;练功组进行新编健身八段锦功法24周干预,每周锻炼6 d,每天90 min的练功;对照组不进行任何运动。观察2组患者试验前后体重、腰围、臀围、体重指数（BMI）、腰臀比（WHR）、空腹血糖（FPG）、糖化血红蛋白（HbAlc）、甘油三脂（TG）、总胆固醇（TC）、低密度脂蛋白（LDL）、高密度脂蛋白（HDL）和人血清视黄醛结合蛋白4（RBP4）等指标的水平变化。结果：练功组试验后其腰围、WHR、FPG、TG、HbAlc和血清RBP4水平与试验前及对照组试验后相比均明显下降（P<0.05）;练功组试验后HDL-C水平与试验前及对照组试验后相比与明显升高（P<0.05）。结论：长期的健身气功八段锦练习可降低肥胖女性糖尿病患者的血糖,对身体的部分肥胖和血脂指标有一定的改善效果。     

Cigarette smoking and serum lipid and lipoprotein concentrations: an analysis of published data.

To examine the association between cigarette smoking in adults and serum lipid and lipoprotein concentrations the results of 54 published studies were analysed. Overall, smokers had significantly higher serum concentrations of cholesterol (3.0%), triglycerides (9.1%), very low density lipoprotein cholesterol (10.4%), and low density lipoprotein cholesterol (1.7%) and lower serum concentrations of high density lipoprotein cholesterol (-5.7%) and apolipoprotein AI (-4.2%) compared with nonsmokers. Among non-smokers and light, moderate, and heavy smokers a significant dose response effect was present for cholesterol (0, 1.8, 4.3, and 4.5% respectively), triglycerides (0, 10.7, 11.5, and 18.0%), very low density lipoprotein cholesterol (0, 7.2, 44.4, and 39.0%), low density lipoprotein cholesterol (0, -1.1, 1.4, and 11.0%), high density lipoprotein cholesterol (0, -4.6, -6.3, and -8.9%), and apolipoprotein AI (0, -3.7 and -5.7% in non-smokers and light and heavy smokers). These dose response effects may provide new evidence for a causal relation between exposure to cigarette smoke and changes in serum lipid and lipoprotein concentrations whether as a direct result of physiological changes or of dietary changes induced by smoking. Adequate prospective data to estimate the excess risk of coronary artery disease existed only for cholesterol concentration. When that information was combined with data from the present study, and given that smokers as a group face an average overall excess risk of coronary artery disease of 70%, it was estimated that the observed increased serum cholesterol concentration in smokers may account for at least 9% of that excess risk. Furthermore, the dose response effect of smoking on serum cholesterol concentration suggests a gradient of increased absolute risk of coronary artery disease between light and heavy smokers.     

Morphine-induced alterations in plasma and tissue cholesterol levels

In rats fed a cholesterol-cholic acid supplemented diet, implantation of a 75 mg morphine pellet elevated total plasma cholesterol, raised low density lipoprotein (LDL) plus very low density lipoprotein (VLDL) cholesterol, and lowered high density lipoprotein (HDL) cholesterol levels. The resultant increase of the atherogenic index was accompanied by enhanced aortic cholesterol deposition. These alterations were prevented by daily administration of naltrexone (1.0 mg/kg, sc), and were not associated with hyperphagic or hepatotoxic actions of morphine. An increase in total plasma cholesterol and in LDL plus VLDL cholesterol was also observed in morphine pelleted rats maintained on a normal diet. The possible implications of opiate-induced hypercholesterolemia are discussed.     

Total cholesterol,low density lipoprotein cholesterol,and high density lipoprotein cholesterol and coronary heart disease in Scotland.

OBJECTIVE--To investigate long term changes in total cholesterol, high density lipoprotein cholesterol, and low density lipoprotein cholesterol concentrations and in measures of other risk factors for coronary heart disease and to assess their importance for the development of coronary heart disease in Scottish men. DESIGN--Longitudinal study entailing follow up in 1988-9 of men investigated during a study in 1976. SETTING--Edinburgh, Scotland. SUBJECTS--107 men from Edinburgh who had taken part in a comparative study of risk factors for heart disease with Swedish men in 1976 when aged 40. INTERVENTION--The men were invited to attend a follow up clinic in 1988-9 for measurement of cholesterol concentrations and other risk factor measurements. Eighty three attended and 24 refused to or could not attend. MAIN OUTCOME MEASURES--Changes in total cholesterol, high density lipoprotein cholesterol, and low density lipoprotein cholesterol concentrations, body weight, weight to height index, prevalence of smoking, and alcohol intake; number of coronary artery disease events. RESULTS--Mean serum total cholesterol concentration increased over the 12 years mainly due to an increase in the low density lipoprotein cholesterol fraction (from 3.53 (SD 0.09) to 4.56 (0.11) mmol/l) despite a reduction in high density lipoprotein cholesterol concentration. Body weight and weight to height index increased. Fewer men smoked more than 15 cigarettes/day in 1988-9 than in 1976. Blood pressure remained stable and fasting triglyceride concentrations did not change. The frequency of corneal arcus doubled. Alcohol consumption decreased significantly. Eleven men developed clinical coronary heart disease. High low density lipoprotein and low high density lipoprotein cholesterol concentrations in 1976, but not total cholesterol concentration, significantly predicted coronary heart disease (p = 0.05). Almost all of the men who developed coronary heart disease were smokers (91% v 53%, p less than 0.05). CONCLUSION--Over 12 years the lipid profile deteriorated significantly in this healthy cohort of young men. Smoking, a low high density lipoprotein concentration and a raised low density lipoprotein concentration were all associated with coronary heart disease in middle aged Scottish men, whereas there was no association for total cholesterol concentration. The findings have implications for screening programmes.     

Dietary lipids and blood cholesterol: quantitative meta-analysis of metabolic ward studies.

OBJECTIVE: To determine the quantitative importance of dietary fatty acids and dietary cholesterol to blood concentrations of total, low density lipoprotein, and high density lipoprotein cholesterol. DESIGN: Meta-analysis of metabolic ward studies of solid food diets in healthy volunteers. SUBJECTS: 395 dietary experiments (median duration 1 month) among 129 groups of individuals. RESULTS: Isocaloric replacement of saturated fats by complex carbohydrates for 10% of dietary calories resulted in blood total cholesterol falling by 0.52 (SE 0.03) mmol/l and low density lipoprotein cholesterol falling by 0.36 (0.05) mmol/l. Isocaloric replacement of complex carbohydrates by polyunsaturated fats for 5% of dietary calories resulted in total cholesterol falling by a further 0.13 (0.02) mmol/l and low density lipoprotein cholesterol falling by 0.11 (0.02) mmol/l. Similar replacement of carbohydrates by monounsaturated fats produced no significant effect on total or low density lipoprotein cholesterol. Avoiding 200 mg/day dietary cholesterol further decreased blood total cholesterol by 0.13 (0.02) mmol/l and low density lipoprotein cholesterol by 0.10 (0.02) mmol/l. CONCLUSIONS: In typical British diets replacing 60% of saturated fats by other fats and avoiding 60% of dietary cholesterol would reduce blood total cholesterol by about 0.8 mmol/l (that is, by 10-15%), with four fifths of this reduction being in low density lipoprotein cholesterol.     

Chemical characterization of the serum very low density and high density lipoproteins from bullfrog, Rana catesbeiana.

The chemical properties of very low density and high density lipoproteins of adult bullfrog serum were determined. This serum contained extremely low levels of both very low density lipoprotein (10-30 mg/100 ml) and high density lipoprotein (5-10 mg/100 ml). The constituents of very low density lipoprotein, on a weight percentage basis, were found to be 48.1% triglyceride, 17.3% cholesterol ester, 8.8% cholesterol, 11.6% phospholipid, and 12% protein. These constituents were also present in high density lipoprotein with weight percentage values of 3.7%, 19.3%, 11.9%, 25.2%, and 36.8%, respectively. The fatty acid compositions of the triglycerides, cholesterol esters, and phosphatidylcholine were quite similar in the very low density lipoprotein and high density lipoprotein. However, shingomyelin fatty acid composition was appreciably different in the two lipoproteins. Disc gel electrophoresis in sodium dodecyl sulfate-polyacrylamide gels produced patterns with one major (approximate molecular weight, 7,000) and several minor bands for the apoprotein of very low density lipoprotein and one major (approximate molecular weight, 28,000) and several minor bands for that of high density lipoprotein.     

原发性肾病综合征高脂血症发生机制的研究进展*

摘要：原发性肾病综合征高脂血症主要表现为血浆总胆固醇（Ch）和低密度脂蛋白胆固醇（LDL-Ch）明显升高,甘油三酯（TG）和极 低密度脂蛋白胆固醇（VLDL-Ch）升高。高密度脂蛋白胆固醇（HDL-Ch）浓度可降低或不变,但HDL的亚型分布异常,即HDL3 增 加而HDL2 减少。这提示我们HDL3 转变为富含CH的HDL2 成熟障碍。不过,关于高脂血症在肾病综合征的发生机制较为复杂, 还不十分清楚。但是目前有关该机制的观点主要集中在（1）低白蛋白血症刺激肝脏合成胆固醇、甘油三酯、脂蛋白增加,（2）外周 脂蛋白的清除障碍,（3）高密度脂蛋白（HDL）的成熟障碍,本文就此做一综述。