苯扎贝特治疗儿童ApoE Tokyo(Arg25Cys)突变型脂蛋白肾病1例

脂蛋白肾病(Lipoprotein glomerulopathy,LPG),1989年首次由日本学者Saito报道,LPG主要累及肾脏,且以肾小球病变为主[1]。几乎所有患者均有不同程度的蛋白尿,多数表现为肾病综合征,少数表现为轻微蛋白尿和镜下血尿,部分患者伴有不同程度的贫血及高血压,血脂异常易被忽略为肾病综合征的低蛋白血症所致。载脂蛋白E(apolipoprotein E,ApoE)增高是LPG血脂改变的主要特点[2-3]。LPG为一种与脂质代谢紊乱密切相关的肾脏疾病,目前世界范围内有报道的病例不足200例,儿童报道仅10余例[2]。本病进展缓慢,临床常误诊为原发性肾病综合征[4]。因此,为增强对LPG的认识,提高诊治水平,现分析1例确诊的儿童LPG临床资料,总结LPG的临床特点、诊断、治疗及预后。     

突聋病人血液流变学及血脂代谢研究

目的探讨血液流变学和血清脂质代谢变化与突发性耳聋(突聋)的关系。方法检测50例突聋病人及50例对照者血液流变学参数及血清中甘油三酯(TG)、总胆固醇(CHO)、高密度脂蛋白胆固醇(HDL-CH)、低密度脂蛋白胆固醇(LDL-CH)、载脂蛋白A(ApoA)、载脂蛋白B(ApoB)和脂蛋白(a)[LP(a)]的含量。结果突聋组全血比粘度、全血还原比粘度、血浆粘度和红细胞压积均增高,与对照组比较差异有显著性(P<0.01);突聋组TG、LDL-CH、ApoB和LP(a)水平较对照组显著增高(P<0.01),HDL-CH较对照组显著降低(P<0.01)。两组间CHO和ApoA无显著性差异(P>0.05)。结论 血液流变学及血脂代谢的异常改变可能与突聋的发生相关。     

人血浆高密度脂蛋白对大鼠内毒素血症的治疗及防护作用研究

目的:观察人血浆高密度脂蛋白(HDL)对大鼠内毒素血症的治疗和防护效果。方法:采用鲎试剂法和放射免疫分析法于3个时点动态测定对照组、治疗组和防护组大鼠血浆内毒素(ET)水平和肿瘤坏死因子(TNF)浓度并观察血压及存活时间。结果:①输注ET后对照组大鼠血压进行性下降(P<0.01);治疗组大鼠输注HDL后其血压虽也降低但下降程度明显弱于对照组(P<0.01);防护组大鼠在输注ET后血压无明显下降(P>0.05)。治疗组及防护组大鼠存活时间均明显长于对照组(P<0.01)。②3组大鼠血浆ET水平在各时点均无明显变化(P>0.05)。③治疗组及防护组大鼠血浆TNFα水平于第3时点均明显降低(P>0.05)。结论:人血浆HDL能减轻或抑制内毒素血症大鼠血压下降并明显延长其存活时间,对内毒素血症具有良好的治疗和防护作用,此作用可能与其抑制TNF释放有关。     

前蛋白转化酶枯草溶菌素9基因多态性的106进展

前蛋白转化酶枯草溶菌素9(PCSK9)是近年来新发现的一种与调节胆固醇代谢密切相关蛋白,属前蛋白转化酶家族。PCSK9可通过调节低密度脂蛋白胆固醇(LDLC)水平进而影响冠状动脉粥样硬化性心脏病、外周血管病、脑血管病、神经系统疾病及糖尿病等疾病的风险。近来研究表明,PCSK9基因多态性位点双向调节胆固醇水平。认识这些多态性位点,对于评估疾病严重性、预后或药物治疗反应有重要临床意义。本文就PCSK9基因多态性及其临床研究进展做一综述。     

Impaired fasting glucose: Pro-diabetic, “atheroprotective” and modified by metabolic syndrome

AIM: To investigate whether impaired fasting glucose (IFG) confers cardiovascular risk.METHODS: A non-diabetic population-based sample representative of middle-aged and elderly Turks was studied at 8.5 years’ follow-up for incident diabetes and coronary heart disease (CHD). Metabolic syndrome (MetS) was defined by ATP-III criteria modified for male abdominal obesity, and IFG and type 2 diabetes were identified by criteria of the American Diabetes Association. Stratification by presence of MetS was used. Outcomes were predicted providing estimates for hazard ratio (HR) obtained by use of Cox proportional hazards regression analysis in models that controlled for potential confounders.RESULTS: In 3181 adults (aged 52 ± 11.5 years at baseline), analysis stratified by MetS, gender and IFG status distinguished normoglycemic subjects by a “hypertriglyceridemic waist” phenotype consisting of significantly higher waist circumference, fasting triglyceride and lower high-density lipoprotein-cholesterol, regardless of gender and MetS. Additionally, lipoprotein (Lp) (a) tended to be lower in (especially female) participants with MetS. Multivariable linear regression in a subset of the sample demonstrated decreased Lp (a) levels to be associated with increased fasting glucose and insulin concentrations, again particularly in women. In Cox regression analysis, compared with normoglycemia, baseline IFG adjusted for major confounders significantly predicted incident diabetes at a 3-fold HR in men and only women with MetS. Cox models for developing CHD in 339 individuals, adjusted for conventional risk factors, revealed that IFG status protected against CHD risk [HR = 0.37 (95%CI: 0.14-0.998)] in subjects free of MetS, a protection that attenuated partly in male and fully in female participants with MetS.CONCLUSION: IFG status in non-diabetic people without MetS displays reduced future CHD risk, yet is modulated by MetS, likely due to autoimmune activation linked to serum Lp (a).     

Pharmacological treatment options for severe hypertriglyceridemia and familial chylomicronemia syndrome

Introduction: A spectrum of disorders, ranging from rare severe cases of homozygous null lipoprotein lipase deficiency (LPLD)–familial chylomicronemia syndrome (FCS) to heterozygous missense LPLD or polygenic causes, result in hypertriglyceridemia and pancreatitis. The effects of mutations are exacerbated by environmental factors such as diet, pregnancy, and insulin resistance.

Areas covered: In this review, authors discuss chronic treatment of FCS by ultra-low fat diets allied with the use of fibrates, omega-3 fatty acids, niacin, statins, and insulin-sensitizing therapies depending on the extent of residual lipoprotein lipase (LPL) activity; novel therapies in development target triglyceride (TG)-rich lipoprotein particle clearance. Previously, a gene therapy approach to LPL-alipogene tiparvovec showed that direct targeting of LPL function reduced pancreatitis events. An antisense oligonucleotide to apolipoprotein-C3, volanesorsen has been shown to decrease TGs by 70–80% and possibly to reduce rates of pancreatitis admissions. Studies are underway to validate its long-term efficacy and safety. Other approaches investigating the role of LPL modulating proteins such as angiopoietin-like petide-3 (ANGPTL3) are under consideration.

Expert opinion: Current therapeutic options are not sufficient for management of many cases of FCS. The availability of antisense anti-apoC3 therapies and, in the future, ANGPTL3 therapies may remedy this.     

非风湿性房颤血栓前血清脂蛋白（a）、脂质过氧化物与红细胞变形能力的检测及临床意义

目的 :探讨非风湿性房颤患者血栓前血清脂蛋白 (a) [L P(a) ]、脂质过氧化物 (L PO)及红细胞变形能力(RCD- IF)的变化对房颤血栓形成的影响及临床意义。方法 :分别对 36例非风湿性慢性房颤患者、4 0例器质性心脏病窦性心律患者及 4 0例健康对照组其 L P(a)、L PO、RCD- IF三项指标进行测定。结果 :非风湿性慢性房颤患者 L P(a)、L PO的升高及 RCD- IF的降低与窦性心律组 (P<0 .0 5 )及对照组 (P<0 .0 1)均存在显著性差异 ;窦性心律组的三项指标与对照组比较其差异亦具显著性 (P<0 .0 5 )。房颤组、窦性心律组两组的 L PO与 RCD- IF均存在相关关系 ;而两组的 L P(a)与 L PO、RCD- IF间无相关关系。结论 :降低 L P(a)、L PO水平及提高 RCD- IF有利于防治房颤患者心房血栓的形成。     

Flow-mediated dilation,carotid wall thickness and HDL function in subjects with hyperalphalipoproteinemia

Background and aimsThe relationships between very high plasma HDLc and subclinical atherosclerosis are still a matter of debate.Methods and resultsTwenty subjects with primary hyperalphalipoproteinemia (HAL, with HDLc in the highest 10th percentile and absence of overt secondary causes of this condition), aged 30–65 years, were compared with 20 age and sex-matched controls. Lipid determination, lipoprotein particle distribution (Lipoprint^®), Cholesterol Efflux Capacity (CEC), plasma adhesion molecule, analyses of CETP, SRB1 and LIPG genes and of different markers of subclinical vascular disease (ankle-brachial index, ABI; carotid intima-media thickness, cIMT; brachial-artery flow mediated dilation, FMD) were performed. Fasting HDLc levels were 40 mg/dl higher in HAL subjects while LDLc concentration was comparable to control group. CETP gene analysis in HAL subjects identified one novel rare Single Nucleotide Polymorphism (SNP, Asp131Asn), possibly damaging, while the common SNP p.Val422Ile was highly prevalent (50% vs. 27.4% in a control population). No rare mutations associated with HAL were found in SR-B1 and LIPG genes. Polyacrylamide gel electrophoresis in HAL subjects disclosed larger and more buoyant HDL particles than in controls, while LDL profile was much more similar. ABI, cIMT and arterial plaques did not differ in cases and controls and the two groups showed comparable FMD at brachial artery examination. Similarly, ABCA1 and ABCG1 HDL-mediated CEC, the most relevant for atheroprotection, did not discriminate between the groups and only ABCG1 pathway seemed somewhat related to arterial reactivity.ConclusionsHDL dimension, function and genetics seem scarcely related to subclinical atherosclerosis and vascular reactivity in middle-aged HAL subjects.