对卵磷脂胆固醇酰基转移酶的全新认识

卵磷脂胆固醇酰基转移酶(lecithin cholesterol acyl transferase,LCAT)作为参与胆固醇逆转运(reverse cholesterol transport,RCT)、高密度脂蛋白(HDL)等脂蛋白代谢的关键酶,在抗动脉粥样硬化(atherosclerosis,AS)的防御系统中起着重要作用。对其的进一步研究将会提高对CHD发生、发展的认识,为CHD的诊治带来新的思路。     

原发性卵磷脂胆固醇酰基转移酶缺乏症

原发性卵磷脂胆固醇酰基转移酶缺乏症是一类卵磷脂胆固醇酰基转移酶基因缺陷导致脂质代谢紊乱的分子病。根据其生物化学和临床表现分为鱼眼病和家族性卵磷脂胆固醇酰基转移酶缺乏症，导致卵磷脂胆固醇酰基转移酶缺陷的基因突变包括碱基置换、缺失和插入。其突变由常染色体隐性遗传。     

卵磷脂胆固醇酰基转移酶与动脉粥样硬化性心血管病

卵磷脂胆固醇酰基转移酶(LCAT)是血浆脂蛋白中催化游离胆固醇酯化的关键酶,在高密度脂蛋白代谢和胆固醇逆转运中起着重要作用。尽管LCAT研究已经进行了半个世纪,其与动脉粥样硬化性心血管病的关系仍存在较大争议。本文就LCAT生物化学特性、在脂代谢中的作用机制、与心血管病的关系及准确测定存在的问题等作一综述。     

血清卵磷脂胆固醇酰基转移酶活性测定及其应用

本文用作者建立的同位素标记法测定人、北京鸭、树鼩血清卵磷脂胆固醇酰基转移酶(LCAT)活性。结果说明鸭血清的LCAT活力比人血清显著为高,同源和异源间有种属差异性,进化上比较接近的动物种属差异性较小。     

卵磷脂胆固醇酰基转移酶基因多态性与脑出血的关系

目的探讨卵磷脂胆固醇酰基转移酶(LCAT)基因511C/T多态性与汉族人群脑出血的关系。方法选择2012年6月至2013年10月该院收治的原发性脑出血患者102例,健康对照120例。采用聚合酶链式反应(PCR)、单链构象多态性(SSCP)和DNA测序法检测LCAT 511C/T基因多态性。采用氧化酶法检测受试者血脂水平。结果脑出血组CT基因型频率为6.87%,对照组为1.67%,脑出血组T等位基因频率为3.43%,对照组为0.83%,组间差异均无统计学意义(P>0.05)。511CC组总胆固醇(TC)水平明显低于511CT组,而高密度脂蛋白胆固醇(HDL-C)水平升高(t=2.524,P=0.013;t=1.871,P=0.049)。在脑出血组中,511CC组HDL-C水平明显高于511CT亚组(t=1.954,P=0.047)。结论 LCAT基因511C/T多态性与脑出血无关,而T等位基因与HDL-C代谢有关。     

人卵磷脂胆固醇酰基转移酶基因在肌源细胞中的表达

为探索人卵磷脂-胆固醇酰基转移酶在骨骼肌细胞表达的可能性，构建了一个由人巨细胞病毒早期增强子和促进子驱动的卵磷脂-胆固醇酰基转移酶cDNA表达质粒。以阳离子介导其转染小鼠肌源性细胞株C2，获得成功表达，并在细胞培养液内测得有生物活性的卵磷脂胆固醇酰基转移酶。提示有可能通过将卵磷脂胆固醇酰基转移酶基因转移至骨骼肌细胞的方法来提高人体内卵磷脂胆固醇酰基转移酶水平。     

血清卵磷脂胆固醇酰基转移酶活性与冠心病的关系

目的探讨血清卵磷脂胆固醇酰基转移酶活性(LCAT)与冠心病(CAD)的关系。方法本研究为病例对照研究。纳入2014年11月至2015年8月在北京医院行冠脉造影的425例患者,按冠状动脉造影结果分为CAD组(341例)和非CAD对照组(84例),应用高效液相色谱法测定血清LCAT活性,分析LCAT活性与CAD及其他危险因素的关系。结果 CAD组中LCAT活性显著高于非CAD组[(37. 3±9. 7)n Kat/L比(34. 8±8. 8)n Kat/L,P=0. 03],两组的高密度脂蛋白胆固醇、Apo AI和随机血糖等均有显著差异(均为P<0. 05)。Spearman相关性分析显示,LCAT活性与体质指数(r=0. 09)、TG(r=0. 30)、Apo B(r=0. 22)和随机血糖(r=0. 09)呈正相关;与HDL-C(r=-0. 26)呈负相关(均为P<0. 05)。单因素logistic回归分析结果显示,LCAT活性升高是CAD危险因素(OR=3. 11,95%CI:1. 40～6. 91,P=0. 005),在校正年龄、性别、HDL-C、Apo AI、随机血糖等危险因素后,多因素logistic回归分析发现LCAT的活性升高仍是CAD危险因素(OR=3. 28,95%CI:1. 27～8. 50,P=0. 014)。结论 LCAT活性升高与冠心病独立相关,但仍需更多研究证实。     

逆转录病毒载体介导人载脂蛋白与卵磷脂胆固醇酰基转移酶基因在骨骼肌的异源性共表达

为探讨人载脂蛋白AI和卵磷脂胆固醇酰基转移酶基因在肌源性细胞中异源共表达的可能性,构建含上述基因和新霉素磷酸转移酶基因的多顺反子重组逆转录病毒载体,以此制备重组病毒颗粒并转染小鼠原代肌母细胞及C2C12肌源性细胞株。酶联免疫吸附法和免疫组织化学检测证实转染后的细胞均具有异源共表达人载脂蛋白AI与卵磷脂胆固醇酰基转移酶的能力,经G418筛选则获得稳定转化的C2C12细胞株,60天后仍能有效共表达人载脂蛋白AI与卵磷脂胆固醇酰基转移酶,聚合酶链反应法检测显示人载脂蛋白AI cDNA与IRES序列均有效整合于靶细胞基因组中,提示以重组逆转录病毒为载体对肌源性细胞进行遗传修饰,再移植回骨骼肌使之在体内长期高效表达载脂蛋白AI和卵磷脂胆固醇酰基转移酶,可能是一种值得探讨的通过促进胆固醇逆转运途径来防止或减轻高脂血症和动脉粥样硬化的方法。     

卵磷脂胆固醇酰基转移酶基因多态性与家族聚集性脑出血及血脂的相关性

目的 探讨卵磷脂胆固醇酰基转移酶基因多态性与湖南地区汉族人群家族聚集性脑出血及血脂的关系.方法 采用聚合酶链反应限制性片长多态性分析法检测湖南地区汉族人群10个有家族聚集现象脑出血家系126例成员、100例散发性脑出血患者和100例正常对照者的卵磷脂胆固醇酰基转移酶608C/T位点基因型分布情况.结果 卵磷脂胆固醇酰基转移酶基因608C/T的CT基因型分布在三个人群均符合Hardy-Weinberg平衡.家系患者及各级亲属组、散发性脑出血组608C/TcT基因型、T等位基因频率与对照组相比差异无显著性(P>0.05).家族聚集现象脑出血组和散发性脑出血组608CC亚组患者高密度脂蛋白胆固醇水平均显著高于同组608CT亚组(P<0.05).结论 卵磷脂胆固醇酰基转移酶基因608C/T位点多态性可能与中国湖南地区汉族人群家族聚集性脑出血无关,T等位基因可能与高密度脂蛋白胆固醇代谢有关.     

姜黄素对食饵性高脂血症大鼠血浆脂蛋白代谢相关酶活性的影响

为了探讨姜黄素降血脂、抗动脉粥样硬化可能的酶学机理．用高脂膳食喂饲Wistar大鼠4周，造成食饵性高脂血症，然后用高、低两种剂量的姜黄素和阳性对照药血脂康、非诺贝特进行实验性治疗。给药3周后处死动物，比较治疗前后血清和肝脏总胆固醇及甘油三酯含量、血清高密度脂蛋白胆固醇和低密度脂蛋白胆固醇含量，同时测定血浆卵磷脂胆固醇酰基转移酶、肝素化血浆总脂解酶、脂蛋白脂酶和肝脂酶活性。结果发现，高、低剂量姜黄素、非诺贝特和血脂康均能使血清总胆固醇、甘油三酯和低密度脂蛋白胆固醇含量降低，降甘油三酯作用高剂量姜黄素和非诺贝特最优，降总胆固醇和低密度脂蛋白胆固醇作用低剂量姜黄素和血脂康最优，高剂量姜黄素和非诺贝特能增加高密度脂蛋白胆固醇含量，同时能降低肝脏总胆固醇和甘油三酯含量。高、低剂量姜黄素能显著提高血浆卵磷脂胆固醇酰基转移酶活性．降低血浆游离胆固醇含量，高、低剂量姜黄素和非诺贝特能提高血浆总脂解酶和脂蛋白脂酶活性，高剂量姜黄素还能显著提高肝脂酶活性。结果提示，姜黄素具有明显的降低肝脏和血清脂质的作用，可能与提高血浆脂蛋白代谢相关酶的活性有关。     

A New Case of Familial LCAT Deficiency

ABSTRACT. Twenty-eight patients with familial lecithin:cholesterol acyltransferase deficiency have been reported to date. We report a new Italian case who presents the clinical and biochemical characteristics of the disease. Typical disc-shaped high density lipoproteins (d= 1.063-1.21 g/ml) were detected by electron microscopy. An abnormal distribution of apolipoproteins in the different lipoprotein fractions was found by sodium dodecyl sulphate polyacrylamide electrophoresis.     

改良的LCAT测定及其在肾脏疾病中的临床意义

用改良Ｓｐｅｒｒｙ自身底物法分别测定了３４例正常人及１５８例肾脏病患者的血清ＬＣＡＴ活性，此法简便、重复性好。联合ＨＤＬ－亚组份检测不失为一种观察各种疾病所致脂质代谢异常的敏感指标。本文测定结果表明，肾脏病患者的血清ＬＣＡＴ活性较正常组显著降低，差异非常显著，证实肾脏疾患时伴有脂酶活性障碍。而且还发现尿黄症、肾炎患者存在低ＨＤＬ血症，尤以ＨＤＬ３降低为明显，而肾病组ＨＤＬ升高，但无统计学意义。唯Ｈ     

Insight into the Role of LCAT from Mouse Models

Reviews in Endocrine and Metabolic Disorders -     

补肾活血方对自发性高血压大鼠血清残粒脂蛋白含量的影响

目的观察补肾活血方对自发性高血压大鼠（SHR）血清残粒脂蛋白（RLP-C）含量的影响。方法给药12周后,采用免疫沉淀分离法测定空白对照组、川芎组、淫羊藿组及补肾活血方组大鼠血清中RLP-C的含量。结果实验12周,与空白对照组比较,各组大鼠血清RLP-C含量均明显降低（P〈0.01）,与川芎组、淫羊藿组比较,补肾活血方组RLP-C含量明显降低（P〈0.01）,川芎组与淫羊藿组相比差异无统计学意义（P＞0.05）。结论补肾活血方、川芎及淫羊藿均能降低SHR血清RLP-C含量,其中补肾活血方作用最强。     

Ageing in India

About 7.6% of India’s population is above 60 years old. The elderly in India face multiple social, political, economic and cultural challenges including suboptimal financial security, decline of traditional extended family systems due to rural-urban migration of young people, and increasing costs of health care. In India, as is the case in many developing countries, the health systems are inadequate to promote, support and protect health and social well-being of the elderly due in part to lack of human and financial resources. The elderly find themselves exposed to harsh realities of globalization; changes in cultural values and beliefs, high disease burden from chronic noncommunicable diseases, and weak family and social welfare system. To address the health and welfare needs of this vulnerable section of society, the Government of India in 1999 developed and adopted the National Policy for Older Persons. A National Council for Older Persons and an Inter-Ministerial Committee was set up to implement the policy directions. To date, Government of India with its partners, have introduced various schemes and initiatives to promote and protect the welfare of the elderly. These initiatives include financial assistance for the construction of and maintenance of old peoples’ homes and non-institutional services to the elderly, as well as the provision of nutritious food and appropriate medical services. The Government of India, through the National Rural Health Mission has embarked on efforts to strengthen provision of primary health services and to reorient health care professionals from curative to preventive services at various levels. However, challenges remain for the health system, social welfare and health financing as the elderly population continue to rise.

Ageing in Place in the United Kingdom

Ageing in Place is a key component of UK policy on older people and housing. Helping older people to ‘age in place’ at home is seen to benefit the quality of life and also provide a cost-effective solution to the problems of an expanding population of very old people. However, the reality is not straightforward and in this paper, some results of qualitative research are presented to illustrate the benefits, problems and challenges that exist in relation to Ageing in Place in the United Kingdom. The research is based on qualitative data collected from 40 people age 80–89 in the north-west of England as part of the ENABLE-AGE Project 2002 to 2004. The research suggests that while Ageing in Place may bring social and psychological benefits, there can also be a significant downside on an everyday level. Home in old age can be a place of negative experiences, such as isolation and loneliness and there are often significant weaknesses in terms of informal support, physical environment of the home and neighbourhood and social network, which undermine the person’s ability to live independently. The paper reviews recent UK initiatives to use “telecare” to address some of these issues.

阿托伐他汀对压力负荷引起高血压大鼠心肌肌浆网钙泵活力的影响

目的观察阿托伐他汀对压力负荷增高所致左心室肥厚(LVH)和心肌肌浆网钙泵(SERCA)活力的影响。方法雄性SD大鼠50只随机分为假手术组、腹主动脉缩窄(AAC)组、阿托伐他汀10mg/(kg·d)(Ato10mg)、阿托伐他汀30mg/(kg·d)(Ato30mg)和氨氯地平5mg/(kg·d)组,每组10只。采用腹主动脉缩窄术建立LVH动物模型,灌胃法给药4周。鼠尾容积法测量收缩压,计算左心室质量指数(LVMI),即左心室质量/体质量(LVM/BM);HE染色检测心肌细胞平均直径;无极磷酸根法测定SERCA活力;双波长荧光分光光度计检测心肌细胞内Ca2+浓度。结果与假手术组相比,AAC组收缩压、LVMI、心肌细胞平均直径、细胞内Ca2+浓度均显著升高,心肌SERCA活力(4.0±0.6)比假手术组(6.4±0.8)μmol/(mgpro.h)明显降低(均P<0.05)。与AAC组比较,阿托伐他汀30mg组及氨氯地平组均能降低大鼠收缩压、LVMI、心肌细胞平均直径和细胞内Ca2+浓度,同时能明显提高心肌SERCA活力[Ato30mg组(4.9±0.4),氨氯地平组(4.8±0.5)比AAC组(4.0±0.6)...     

Analysis of the Effect of Ageing on Rising Edge Characteristics of the Photoplethysmogram using a Modified Windkessel Model

Ageing is one of the main contributing factors towards increasing arterial stiffness, leading to changes in peripheral pulses propagation. Therefore the characteristics of the photoplethysmogram (PPG) pulse, especially the rising edge and peak position, are greatly affected. In this study, the PPG pulse rising edge and corresponding peak position have been investigated non-invasively in human subjects as a function of age. Fifteen healthy subjects were selected and grouped in five age intervals, from 20 to 59 years, based on their comparable systolic-diastolic blood pressure and PPG amplitude. As expected, the peripheral pulse shows a steep rise and early peak in younger subjects. With age, the slope becomes blunted and in older subjects, the rise is very gradual and the pulse peak appears much later. Qualitative results were further verified by a modified 10-element Windkessel model to quantify the lumped parameter changes with ageing. This verification highlighted some specific changes in vascular parameters with aging. The rising edge could be considered as one parameter in determining the age-dependent vascular state.     

Ageing of the postural vertical

A postural vertical (PV) tilted backward has been put forward as a reason explaining the backward disequilibrium often observed in elderly fallers. This raises the question of a possible ageing process of the PV involving a backward tilt of verticality perception increasing with age. We have explored this hypothesis by measuring PV in pitch using the wheel paradigm in 87 healthy subjects aged from 20 to 97 years. The possibility that this physiological ageing accelerated in the second part of life was also analysed. Two indices were calculated: the mean orientation (PV-orient) and the dispersion (PV-uncert). The correlation between age and PV-orient was r = −0.2 (p < 0.05). Added to the fact that PV was twice as shifted backward in the 38 seniors over 50 years (−1.15° ± 1.40°) as in the 49 young adults under 50 years (−0.45° ± 0.97°; t = 2.75, p < 0.01), this indicates the existence of a physiological ageing process on the direction perceived as vertical by the whole body, with a slight backward shift of PV throughout the life span. The correlation between age and PV-uncert was r = 0.35 (p < 0.001) in all subjects and r = 0.59 (p < 0.001) in seniors. This indicates that subjects get less and less accurate in their perception of the postural vertical with age, especially very old subjects who show great uncertainty in determining with their body the direction of the vertical. Taken together, these findings indicate that the internal model of verticality is less robust in elderly people. This may play a part in their postural decline.