2代3人同患家族性高胆固醇血症及其低密度脂蛋白受体基因突变分析

目的　调查姐妹二人同患家族性高胆固醇血症的家系并进行系谱分析。方法　根据患者及其家系的血缘关系绘制家系图谱,分析临床症状和血脂检查资料。结果　先证者女性,17岁,血清胆固醇浓度为18.89 mmol/L,3岁时即有臀部黄色瘤, 17岁时首次发生前壁心肌梗死,其姐血清胆固醇浓度为15.23 mmol/L,全身多处黄脂瘤。初步诊断先证者为纯合子型,其姐为杂合型。检查患儿4代29人,根据血脂和临床表现确诊2例杂子型家族性高胆固醇血症患者,系谱分析该家系遗传方式符合常染色体显性遗传规律。结论　初步证实一个纯合子型家族性高胆固醇血症系谱。     

Functional analysis of low-density lipoprotein receptor in homozygous familial hypercholesterolemia patients with novel 1439 C→T mutation of low-density lipoprotein receptor gene

Background Familial hypercholesterolemia （FH）, caused by low density lipoprotein （LDL） receptor （LDL-R） gene mutations, is associated with increased risk of premature coronary heart disease. Until now, limited molecular data concerning FH are available in China. The present study described the clinical profiles and cell biological defects of a Chinese FH kindred with novel LDL-R gene mutation. Methods The patient＇s LDL-R gene coding region was sequenced. The patient＇s lymphocytes were isolated and the LDL-R expression, binding and up-take functions were observed by immunohistochemistry staining and flow cytometry detection. The patient＇s heart and the major large vessels were detected by vessel ultrasound examination and myocardial perfusion imaging （MPI）. Results The patient＇s LDL-R expression, LDL binding and up-take functions were significantly lower than normal control （39%, 63% and 76% respectively）. A novel homozygous 1439 C→T mutation of the LDL-R gene was detected in the patient and his family. ECG showed atypical angina pectoris. Echocardiogram showed stenosis of the coronary artery and calcification of the aortic valve and its root. Blood vessel ultrasound examination showed the thickness of large vessel intima, and the vessel lumen was narrowed by 71%. MPI showed ischemic changes. Conclusions The LDL-R synthesis dysfunction of FH patients leads to arterial stenosis and calcification, which are the major phenotype of the clinical disorder. The mutation of the LDL-R gene is determined. These data increase the mutational spectrum of FH in China.     

China, Japan sign agreement to share marrow donation information

Background Familial hypercholesterolemia (FH) is a type of dominant autosomal disease that causes high levels of plasma low-density lipoprotein cholesterol (LDL-C). In the past years, molecular data related to FH were limited in China. Now, to gain more information about FH, we analyzed one proband with a severe FH phenotype as well as his relatives. Methods After the entire coding sequence and the intron-exon junctions of the low-density lipoprotein receptor (LDLR) gene were amplified using PCR, we sequenced the LDLR gene of a Chinese FH family. RT-PCR was used to detect changes in the mRNA.Results Two novel mutations were identified in the LDLR gene of this family. One, W165X, was a G>A substitution at the third nucleotide of codon 165. The other, IVS5–1G>A, was also a G>A substitution at the acceptor splice site of intron 5. The most striking discovery is that the proband was heterozygous for W165X but homozygous for IVS5–1G>A. The cDNA sequencing showed that the IVS5–1G>A mutation caused the insertion of 10 nucleotides, namely GCTCTCACAA, between exon 5 and exon 6. Conclusions The two nucleotide variations are thought to be the FH-causing mutations because the co-segregation of the mutant allele with the phenotype of FH has been shown in this Chinese family. These data show an increase in the mutational spectrum of FH in China and verify a scarce mutational form in the LDLR gene.     

家族性高胆固醇血症的诊断及治疗研究进展

家族性高胆固醇血症(FH)是脂蛋白代谢异常所导致的遗传性疾病,通常为常染色体显性遗传,由于长期暴露于高水平低密度脂蛋白下,FH患者发生冠状动脉疾病的风险显著升高。基因检测对FH的诊断至关重要,除此之外,低密度脂蛋白受体功能检测对FH的治疗也具有重要意义。本文将从FH的诊断筛查、治疗方案及低密度脂蛋白受体功能检测等方面进行综述。     

A novel mutation in proprotein convertase subtilisin/kexin type 9 gene leads to familial hypercholesterolemia in a Chinese family

Background Familial hypercholesterolemia （FH） is an autosomal disorder associated with elevated plasma low density lipoprotein （LDL） levels leading to premature coronary heart disease （CHD）. As a result of long-term hyperlipemia, FH patients will present endarterium thickening and atherosclerosis. In the present study we scanned the related gene of a clinically diagnosed autosomal genetic hypercholesterolemia family for the possible mutations and established eukaryotic expression vector of mutation of proprotein convertase subtilisin/kexin type 9 （PCSK9） gene with gene recombination technique to investigate the contributions of the variation on low density lipoprotein receptor （LDL-R） metabolism and function alternation.Methods Mutation detection was conducted for LDL-R, apolipoprotein B100 （apoB100） and PCSK9 gene with nucleotide sequencing in a Chinese FH family. The full-length cDNA of wild type PCSK9 gene （WT-PCSK9） was obtained from Bel-7402. Site mutagenesis was used to establish the recombinant eukaryotic expression vector carrying pathogenic type of PCSK9 gene and the inserted fragment was sequenced. With the blank vector as control, liposome transfection method was used to transfect the Bel-7402 cells with recombinant plasmid. The expression of LDL-R mRNA was examined by RT-PCR. PCSK9 and the expression of LDL-R protein were determined by Western blotting. Results The G→T mutation at the 918 nucleotide of PCSK9 gene resulted in the substitution of the arginine by a serine at the codon 306 of exon 6. After sequencing, it was confirmed that the inserted fragment of established expression vector had correct size and sequence and the mutant was highly expressed in Bel-7402 cells. There was no significant variation in the levels of LDL-R mRNA. LDL-R mature protein was decreased by 57% after the cells were transfected by WT-PCSK9 plasmid. Mature LDL-R was significantly decreased by 12% after the cells were transfected by R306S mutant as evidenced by gray scale scanning, suggesting that the new mutant R306S can significantly decrease the expression of mature LDL-R protein.Conclusions A novel missense mutation of PCSK9 gene, R306S, was found and the eukaryotic expression vectors of mutant and wild-type of PCSK9 gene were established. There was no significant variation in the levels of LDL-R mRNA. The R306S mutation could significantly lead to the decrease of LDL-R mature protein expression, which might be the pathogenic gene of the FH family.     

降胆固醇药物对冠脉硬化病人低密度脂蛋白受体基因表达的影响

目的 研究降胆固醇药物对低密度脂蛋白受体（ＬＤＬＲ）基因表达的影响。方法 应用逆转录多聚酶链反应（ＲＴ－ＰＣＲ）检测冠状动脉硬化病人和正常对照组外周血单个核细胞ＬＤＬＲ ｍＲＮＡ水平,同时检测血脂水平。结果 他汀类降胆固醇药物显著降低冠脉硬化组总胆固醇及低密度胆固醇水平的同时,增加ＬＤＬＲ ｍＲＮＡ水平。结论 他汀类降胆固醇药物可通过增加低密度脂蛋白受体基因的转录,增加胆固醇清除,参与降低体内胆固     

Determinants of low-density lipoprotein cholesterol goal attainment: Insights from the CEPHEUS Pan-Asian Survey

BackgroundPrevious studies have reported that the attainment of goals for low-density lipoprotein cholesterol (LDL-C) are globally suboptimal, but contemporary data are scarce. The CEntralized Pan-Asian survey on tHE Under-treatment of hypercholeSterolemia (CEPHEUS-PA) is the largest evaluation of pharmacological treatment for hypercholesterolemia in Asia. The study reported here analyzed the Taiwan cohort in CEPHEUS-PA to identify the determinants of successful treatment.MethodsThe patients eligible for this study were adults (≥18 years old) with hypercholesterolemia and with at least two coronary heart disease (CHD) risk factors who had been receiving lipid-lowering drugs for at least 3 months before enrollment, without adjustment for at least 6 weeks before enrollment. Demographic and clinical information and lipid concentrations were recorded. Cardiovascular risk levels and LDL-C targets were determined using the updated Adult Treatment Panel III.ResultsIn this group of 999 Taiwanese patients, 50%, 25%, and 24% had LDL-C goals set at <70 mg/dL, <100 mg/dL, and <130 mg/dL, respectively. The overall attainment rate was 50%, with the lowest rate in patients set at the most stringent target (22%), followed by those whose therapeutic goals were <100 mg/dL (69%) and <130 mg/dL (87%). The success of LDL-C control was lower in patients with multiple risk factors other than CHD or its equivalents than in those without these multiple risk factors (37% vs. 53%, p < 0.001), and lower in patients with metabolic syndrome than in those without (43% vs. 66%, p < 0.001). Baseline LDL-C and cardiovascular risk were inversely associated with goal attainment, whereas treatment with statins was directly associated with the achievement of LDL-C goals. Patients with diabetes (odds ratio 0.49, 95% confidence interval 0.29–0.84, p = 0.010) and with metabolic syndrome (odds ratio 0.15, 95% confidence interval 0.05–0.40, p < 0.001) were less likely to be treated with statins.ConclusionThis study showed that there is a discrepancy between the updated Adult Treatment Panel III recommendations for LDL-C control and the control attained by this group of Taiwanese patients. In particular, treatment with statins was largely underused in patients with diabetes and in those with metabolic syndrome. These findings highlight the need for more intensive treatment in high-risk patients and those with multiple risk factors, particularly patients with metabolic syndrome.     

脑卒中及其危险因素与小而密低密度脂蛋白关系的研究

目的探讨血浆小而密低密度脂蛋白（sdLDL）与脑卒中及其他危险因素的关系。方法采用全自动生化分析仪检测112例脑卒中患者的血浆sdLDL水平,患者均经头颅CT和核磁共振检查证实脑卒中,其中缺血性脑梗死54例,腔隙性脑梗死32例,脑出血26例。对照组120例,性别、年龄匹配并经严格检查排除了脑卒中。观察各组间sdLDL的变化及其与预后的关系,对sdLDL的影响因素采用多元逐步回归进行分析。结果缺血性脑梗死组和腔隙性脑梗死组的血浆sdLDL水平为（1.65±0.31）mmol/L和（1.13±0.21）mmol/L明显高于对照组（0.39±0.14）mmol/L（P〈0.01）;脑出血组的血浆sdLDL水平（0.48±0.19）mmol/L与对照组比较差异无统计学意义（P〉0.05）。多元逐步回归分析显示,危险因素中的甘油三酯、年龄、收缩压、高密度脂蛋白和低密度脂蛋白影响血浆sdLDL水平（P〈0.05）。Logistic回归分析结果显示,sdLDL/LDL〉50%者发生缺血性脑梗死的危险性增加（OR值=3.7,95%可信区间2.672～5.214,P〈0.001）;sdLDL异常与腔隙性脑梗死和脑出血的关系无统计学意义（P〉0.05）。结论 sdLDL水平与缺血性脑梗死的发生密切相关,可能是缺血性脑梗死的独立危险因素。     

Fluvastatin prevents renal injury and expression of lactin-like exidized low-density lipoprotein receptor-1 in rabbits with hypercholesterolemia

Background Lipid abnormalities are often complicated by renal dysfunction. 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are the first-line choice for lowering cholesterol levels. The present study was designed to investigate whether statins could prevent and invert the development of renal injury in cholesterol-fed rabbits and to find the possible mechanism of their effects by detecting gene and protein expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) in the renal artery.Methods Twenty-four male New Zealand white rabbits were divided into three groups: (1) control group, regular granules chow; (2) HC-diet group, granules chow with 1% cholesterol and 5% lard oil; and (3) fluvastatin group, 1% cholesterol and 5% lard oil diet plus fluvastatin ［10 mg·kg（-1）·d（-1）］ . After 16 weeks, serum total cholesterol (TC), low-density lipoprotein(LDL) and creatinine (Cr) levels were measured. Renal hemodynamics and function, mainly including glomerular filtration rate (GFR) in vivo were quantified using 99mTc-DTPA single photon emission computed tomograph (99mTc-DTPA SPECT). The thickness of the renal artery intima was quantitated in HE-stained segments by histomorphometry. Gene expression of LOX-1 in the renal artery was examined by semi-quantitative RT-PCR and its protein expression was evaluated by immunohistochemistry.Results High cholesterol diet induced hypercholesterolemia (HC) complicated by renal dysfunction with increased levels of serum lipid and Cr, decreased GFR and delayed excretion and extensively thickened renal arterial intima in the HC-diet group. Rabbits in the control group showed a minimal LOX-1 expression (mRNA and protein) in the endothelium and neointima of the renal artery. Intimal proliferation of the renal artery in the HC-diet group was associated with a marked increase of LOX-1 expression (protein and mRNA). Treatment with fluvastatin improved renal function, attenuated intimal proliferation of the renal artery and markedly decreased the enhanced LOX-1 expression in the endothelium and neointima of the renal artery in rabbits. Conclusions Fuvastatin treatment could prevent the development of renal injury in patients with HC and early atherosclerosis (AS). This beneficial effect might be mediated by its pleiotropic effects including a decrease in total cholesterol exposure level and prevention of LOX-1 expression in atherosclerotic arteries.     

HDL影响冠心病患者血小板ox-LDL诱导活化的体外分析

目的 探讨高密度脂蛋白(HDL)对氧化低密度脂蛋白(ox-LDL)诱导的人血小板活化的影响.方法 将洗涤血小板按照等体积分为3组,Ⅰ组加入100 μg/mL HDL;Ⅱ、Ⅲ组均加入PBS,3组均置于37℃环境下孵育15 min.Ⅰ、Ⅱ组加入50μg/mL ox-LDL;Ⅲ组加入PBS,3组均在37℃再孵育15 min.应用流式细胞仪检测3组CD62P表达水平,应用透射电镜观察3组血小板的形态结构.结果 3组的血小板CD62P表达率差异有统计学意义(P＜0.05),且Ⅱ组(29.26±5.91)％＞Ⅰ组(15.37±1.49)％＞Ⅲ组(2.05±0.85)％3组的血小板CD62P平均荧光强度(MFI)存在差异(P＜0.05),且Ⅱ组(3.97±0.64)＞Ⅰ组(2.51±0.53)＞Ⅲ组(1.50±0.10).Ⅱ组血小板脱颗粒比Ⅰ组更明显,Ⅲ组未发生脱颗粒.结论 HDL能显著抑制ox-LDL体外诱导的血小板活化.     

氧化低密度脂蛋白诱导心肌炎反应的研究

目的探讨氧化低密度脂蛋白（ox-LDL）对乳鼠心肌细胞炎症反应的影响。方法原代培养乳鼠心肌细胞,用不同浓度的ox-LDL干预24小时和同一浓度ox-LDL干预24～72小时。用RT-PCR、免疫细胞化学染色,观察ox-LDL对细胞PPAR-ymRNA和TNF-amRNA的表达、NF_KB活化的影响。结果ox-LDL可诱导心肌细胞TNF_amRNA表达及NF-KB活化,并可抑制PPAR—ymRN表达,与对照组比较有显著性差异性（P〈0．05）。BSA组与空白对照组比较差异无显著（P〉0．05）。随着ox-LDL浓度和时间的增加,各ox-LDL组间比较有显著差异（P〈0．05）。结论ox-LDL能上调心肌细胞TNF-amRNA及NF-κB活化,并可抑制PPAR-γmRN袁达,提示ox-LDL在糖尿病心肌病的发生中可能具有重要的作用。     

氧化型低密度脂蛋白调控MerTK受体表达抑制巨噬细胞对凋亡细胞的吞噬

目的 研究氧化型低密度脂蛋白(ox-LDL)对巨噬细胞吞噬清除凋亡细胞的作用及其机制.方法 RAW264.7小鼠巨噬细胞随机分为对照组(无血清的DMEM培养液)、10 μg/mL ox-LDL组(10 μg/mL ox-LDL无血清DMEM培养液)和20 μg/mLox-LDL组(20 μg/mL ox-LDL无血清DMEM培养液),采用紫外光照射诱导RA W264.7小鼠巨噬细胞发生凋亡,流式细胞分析法检测RAW264.7小鼠巨噬细胞对凋亡细胞的吞噬指数,Western blotting和Real-Time PCR技术分别检测促吞噬受体MerTK蛋白和mRNA表达的变化.结果 ①孵育24h后,10 μg/mL ox-LDL组和20 μg/mL ox-LDL组吞噬指数分别较对照组下降(4.7±2.8)％和(12.6±2.2)％,20μg/mL ox-LDL组显著小于对照组和10 μg/mL ox-LDL组(P＜0.05).②孵育24 h后,10μg/mLox-LDL组和20 μg/mL ox-LDL.组MerTK蛋白表达灰度值分别较对照组下降(20.0±16.5)％和(47.0±15.4)％,20 μg/mLox-LDL组显著小于对照组(P＜0.05).③孵育12h后,10 μg/mL ox-L.DL.组和20 μg/mL ox-LDL组MerTK mRNA相对表达量分别较对照组减少(33.0±17.5)％和(60.0±10.0)％,10 μg/mL ox-LDL组和20 μg/mL ox-LDL组均显著小于对照组(p均＜0.05).结论 ox-LDL可抑制巨噬细胞对凋亡细胞的吞噬功能,其机制与抑制促吞噬受体MerTK的表达有关,这也可能是ox-LDL致动脉粥样硬化斑块不稳定和进展的机制之一.     

低密度脂蛋白-胆固醇达标的冠心病患者脂蛋白(a)水平与冠脉病变复杂程度的相关性研究

目的:探讨低密度脂蛋白-胆固醇达标的冠心病患者脂蛋白（a）水平与冠脉病变复杂程度的相关性。方法:收集低密度脂蛋白-胆固醇已达标的212例行冠脉造影的冠心病患者临床资料,根据SYNTAX评分将患者分为低危组（0～22分）104例和中高危组（≥23分）108例,采用Pearson相关分析血脂指标与SYNTAX评分的相关性,绘制ROC曲线评估脂蛋白（a）对冠脉病变复杂程度的预测价值并确定最佳临界值。采用多因素Logistic回归分析脂蛋白（a）与冠脉病变复杂程度的关系。结果:中高危组脂蛋白（a）水平高于低危组[28.55（13.98,52.00）nmol/L vs.13.55（8.10,33.60）nmol/L（P <0.01）]。Pearson相关分析显示,脂蛋白（a）水平与SYNTAX评分呈正相关（r =0.235,P <0.01）。ROC曲线显示,脂蛋白（a）预测冠状动脉病变复杂程度的曲线下面积为0.653（95%CI:0.580~0.727,P<0.01）,最佳临界值12.70 nmol/L,灵敏度78.7%,特异度49%。多因素Logistic回归分析结果显示,脂蛋白（a）是冠脉病变复杂程度的独立危险因素（OR=2.734,95%CI:1.358~5.504,P <0.01）。结论:低密度脂蛋白-胆固醇达标的冠心病患者中脂蛋白（a）是冠状动脉病变复杂程度的独立危险因素,为冠心病药物治疗提供了新靶点。     

冠心病患者血清脂蛋白（a）与氧化低密度脂蛋白水平的临床研究

目的探讨冠心病患者血清脂蛋白（a）与氧化低密度脂蛋白水平的变化及临床价值。方法选取我院收治的冠心病患者65例作为研究对象,另选择健康体检者25例作为对照组,分别测定两组患者血清脂蛋白（a）[Lp（a）]、氧化低密度脂蛋白（ox-LDL）及其他血脂指标,并对检测结果进行分析。结果冠心病各临床类型患者血清Lp（a）和OX-LDL水平均显著高于正常对照组,组间比较差异有统计学意义（P〈0．05或〈0．01）。结论冠心病患者血清Lp（a）和OX-LDL水平均明显升高,联合检测脂蛋白（a）及OX-LDL对预测冠心病的发生具有重要意义。     

家族性高胆固醇血症纯合子患者低密度脂蛋白受体缺陷的研究

目的：研究家族性高胆固醇血症纯合子患者的发病机理。方法：在临床研究和家系调查的基础上, 培养患者皮肤成纤维细胞, 采用放射性配体结合受体分析技术研究其低密度脂蛋白受体。结果：患者低密度脂蛋白受体对低密度脂蛋白的高亲和性结合为正常人的７８．２％，高亲和性内移和降解则分别为正常人的３．６％和１．７％。结论：本例家族性高胆固醇血症纯合子患者的发病机制为低密度脂蛋白受体内移功能障碍。     

氧化低密度脂蛋白对人肾小球系膜细胞A型清道夫受体表达的调节作用

目的研究氧化低密度脂蛋白(Ox-LDL)对人肾小球系膜细胞(HMC)A型清道夫受体(SR-A)表达的调节作用,探讨在慢性肾脏疾病中Ox-LDL加重肾病进展的作用机制.方法脂质体转染含SR-A cDNA的表达质粒,建立稳定高表达SR-A的人肾小球系膜细胞株(HMCL),油红"O"染色检测HMCL对Ox-LDL的摄取;RT-PCR法检测Ox-LDL和LDL对HMC SR-A mRNA表达的作用.结果稳定高水平表达SR-A的HMCL对Ox-LDL的摄取明显强于未转染细胞;Ox-LDL上调HMC SR-A mRNA的表达,作用于24 h达到高峰;Ox-LDL(10～100μg/ml)作用24 h对HMC SR-A mRNA的上调作用呈剂量依赖性;天然LDL对SR-A的表达无明显影响.结论在HMC,SR-A是Ox-LDL进入细胞内的主要受体之一,Ox-LDL具有上调HMC SR-A mRNA表达的作用,推测在慢性肾脏疾病进展中,局部沉积的LDL经氧化修饰后可能通过刺激SR-A的表达进入细胞内增强其对HMC的毒性作用,进而加重肾小球硬化的进展.     

点突变导致Rb1基因内部密码形成终止

本实验中使用聚合酶链反应—单链构象多态（ＰＣＲ—ＳＳＣＰ）联合序列分析对视网膜母细胞瘤肿瘤组织Ｒｂｌ基因进行检测时，发现Ｒｂｉ基因第６Ｐ外显子内Ｔ至Ｇ，点突变、第２３外显子内Ｇ至Ｔ点突变，其结果导致Ｒｂｌ基因编码序列终止密码的形成，这种改变无疑使Ｒｂｌ基因的完整表达受挫。     

罗格列酮对高脂血症家兔低密度脂蛋白氧化的影响

目的研究罗格列酮对高脂血症家兔低密度脂蛋白氧化的影响。方法采用高脂饮食建立家兔高脂血症模型,观察罗格列酮对血清脂质水平、血清总抗氧化能力(TAC)及血清氧化低密度脂蛋白(Ox-LDL)水平的影响;超速离心法分离低密度脂蛋白(LDL),采用铜离子进行氧化,观察罗格列酮对LDL氧化易感性的影响。结果罗格列酮可显著提高高脂血症家兔血清TAC,增强LDL抗氧化能力,降低血清Ox-LDL水平,但对血清总胆固醇(TC)等脂质水平无明显影响。结论罗格列酮可有效抑制高脂血症家兔LDL氧化,其机制与提高血清总抗氧化能力、降低LDL氧化易感性有关。     

血清低密度脂蛋白与脑出血血肿扩大的相关性研究

目的 探讨脑出血急性期血肿扩大与血清低密度脂蛋白(LDL-C)的相关性.方法 采用回顾性分析,收集天津市环湖医院神经内科发病6h内行第一次头CT检查,24 h内复查头CT的脑出血患者资料,共360例.按入院时LDL-C水平是否＜2.49 mmol/L分为LDL-C≥2.49 mmol/L组(212例)和LDL-C＜2.49mmol/L组(148例),对两组患者的年龄、性别、入院时收缩压(SBP)、舒张压(DBP)、血肿体积、凝血酶原时间(PT),部分活化凝血酶时间(APTT),纤维蛋白原(FIB)、血小板数(PLT)、血糖及是否有血肿扩大进行对比分析;按24 h内是否有血肿扩大分为血肿扩大组(53例)和非血肿扩大组(307例),将两组的LDL-C水平进行两样本均数比较的t检验.结果 LDL-C≥2.49 mmol/L组和LDL-C＜2.49 mmol/L组间的年龄、性别、入院时SBP、DBP、血肿体积、PT、APTT、FIB、PLT和血糖比较差异无显著性(P＞0.05);LDL-C＜2.49 mmol/L组的血肿扩大发生率明显高于LDL-C≥2.49 mmol/L组,差异有显著性(P＜0.01);血肿扩大组和非血肿扩大组间LDL-C平均水平比较差异有显著性(P＜0.01).结论 对入院后LDL-C＜2.49 mmol/L的脑出血患者应警惕是否有血肿扩大发生,并采取相应的治疗措施,改善患者的预后.     

低密度脂蛋白诱导大鼠系膜细胞增殖与COX-2表达的关系

目的观察LDL刺激下大鼠系膜细胞的增殖情况和COX-2 mRNA和蛋白表达水平的变化。探讨COX-2表达和LDL、系膜细胞增殖之问的关系。方法以体外培养的大鼠系膜细胞为研究对象。应用不同浓度的LDL刺激系膜细胞。应用MTT法检测细胞增殖；应用KT-PCK和Westem Blot的方法检测COX-2 mKNA和蛋白的表达。分析COX-2 mRNA和蛋白的表达与LDL浓度、系膜细胞增殖的相关性。结果以浓度为3．125-100．000μg／mL的LDL刺激系膜细胞，可促进系膜细胞的增殖，在LDL 0．000-50．000μg／mL的浓度范围内，系膜细胞的增殖和LDL的浓度呈正相关；以浓度为3．125-100．000μg／mL的LDL刺激系膜细胞，可上调COX-2 mRNA和蛋白的表达。在LDL0．000-50.000μg／mL的范围内，COX-2 mRNA和蛋白的表达与LDL浓度、系膜细胞增殖呈正相关。结论LDL可以诱导系膜细胞增殖，上调COX-2表达，在LDL 0．000-50．000μg／mL的范围内，系膜细胞增殖与LDL浓度具有相关性，COX-2的表达与LDL浓度、系膜细胞增殖具有相关性。