Function and significance of very low density lipoprotein receptor subtype II

Summary To explore the functions of very low density lipoprotein receptor (VLDL-R) subtype II in lipoprotein metabolism and foam cells formation, the recombinant plasmid with the two subtypes cDNA was constructed respectively, the ldl-A7 cell lines were transfected and two cell lines expressing VLDL-R were obtained: one stably expressing the VLDLR with the O-linked sugar region (type I VLDLR) and the other without the O-linked sugar region (type II VLDLR). In the study on binding of VLDLR to their nuclein labeled natural ligands (VLDL and β-VLDL), it was found that surface binding of¹²⁵I-VLDL or¹²⁵I-β-VLDL of ldl-A7 cells transfected with type II VLDLR recombinant (ldl-A7-VRII). After being incubated with VLDL for different time, the contents of triglyceride and total cholesterol in cells were mensurated, and the formation of foam cells and accumulation of lipid in cells was observed by oil-red O staining. The results showed that the contents of triglyceride and total cholesterol in ldl-A7-VR I were much higher than those in ldl-A7-VR II, and ldl-A7-VR I could transform into foam cells notably. It was suggested that type I VLDLR binds with relative higher affinity to VLDL and β-VLDL, and internalizes much mor elipoprotein into cells. As a result, we can conclude that type I VLDLR plays a more important role in lipoprotein metabolism and foam cells formation than type II VLDLR. TIAN Jun, male, born in 1969, M. D., Ph. D. This project was supported by a grant from National Natural Sciences Foundation of China (No. 30300134).     

极低密度脂蛋白对大鼠系膜细胞增殖的作用

目的:研究极低密度脂蛋白(VLDL)对SD大鼠系膜细胞(MCs)的促增殖作用.方法:采用MTT法测定不同浓度VLDL在不同时间对MCs的促增殖作用,采用流式细胞术观察VLDL诱发MCs凋亡的情况.结果:不同浓度VLDL(10～500 μg/ml)在不同时间(6～48 h)与MTT光密度值呈线性关系,r分别为0.911(P<0.01)、0.651(P<0.05).当VLDL浓度达1 000 μg/ml时,MCs出现凋亡.结论:在一定浓度内VLDL可以时间剂量依赖性地促进MCs的增殖,但高浓度则可促进细胞凋亡.     

巨噬细胞源性载脂蛋白E在VLDL亚组份代谢中的作用

高甘油三酯（TG）血症患者血中升高的极低密度脂蛋白（VLDL）主要是贫含载脂蛋白E（ApoE）的亚组份。为研究巨噬细胞（MΦ）分泌的ApoE在其代谢VLDL中的作用，将贫含ApoE的VLDL和富含ApoE的VLDL分别与MΦ保温24h，然后测定细胞内脂质和ApoEmRNA含量。结果显示：二种亚组份所引起的MΦ内胆固醇堆积程度相当（P＞0．05）；二种亚组份也均能引起MΦ内ApoEmRNA表达增加，尤以贫含ApoE的VLDL作用显著（P＜0．05）。提示：贫含ApoE的VLDL可能促进MΦ产生更多的ApoE，进而在局部结合更多的ApoE转变为类似富含ApoE的VLDL，通过ApoE介导的受体进入MΦ，使MΦ堆积脂质。由此推测MΦ产生ApoE的功能之一是促进自身对VLDL亚组份的摄取。     

低密度及氧化低密度脂蛋白对内皮细胞分泌肾上腺髓质素的影响

目的探讨低密度及氧化低密度脂蛋白对内皮细胞分泌肾上腺髓质素(ADM)的影响.方法利用培养的内皮细胞株ECV-304细胞,分别与不同浓度的低密度(50 100mg/L)、氧化低密度脂蛋白(50 100mg/L)及低密度脂蛋白(50 mg/L) 氧化低密度脂蛋白(50 mg/L)进行孵育,24 h后分别收集培养上清及细胞,用放免分析检测上清及细胞内肾上腺髓质素的含量.结果低密度脂蛋白对肾上腺髓质素的分泌无影响,而氧化型低密度脂蛋白能明显刺激ADM的分泌,二者合用的作用接近于100mg/L的OX-LDL.结论OX-LDL可能具有氧化LDL使其成为OX-LDL的作用,ADM的分泌可能是对细胞损伤的一种反应.     

大鼠肝星状细胞LDL、HDL受体的测定

研究大鼠肝星状细胞ＬＤＬ、ＨＤＬ受体。方法用链霉蛋白酶和胶原酶原位灌流,Ｎｙｃｏｄｅｎｚ密度梯度离心分离大鼠ＨＳＣ,应用＾１２３Ｉ－ＬＤＬ和＾１２５Ｉ－ＨＤＬ３配体进行放射性配基结合实验测定ＨＳＣＬＤＬ、ＨＤＬ受体。     

Proliferation of renal mesangial cells induced by very low density lipoprotein is mediated by p42/44 mitogen activated protein kinase

Background The plasma concentration of very low density lipoprotein （VLDL） is negatively correlated to renal function in glomerular diseases. Effects of VLDL on renal function have been partially attributed to the proliferation of mesangial cells. This study examined the potential role of the p42/44 mitogen activated protein kinase （MAPK） in mesangial cell proliferation induced by VLDL. Methods Mesangial cells were treated with VLDL at different concentrations or for different time. The cell cycle of the mesangial cells was analyzed by Xl-r assay and flow-cytometry; MAPK activity was also assayed. In some experiments, cells were treated with VLDL together with or without 0.1 pmol/L PD 98059. Results Ten to 500 μg/ml VLDL stimulated the proliferation of mesangial cells cultured in vitro in a concentration-dependent manner. The effect was associated with an increase in p42/44 MAPK activity. Increased proliferation of mesangial cells by VLDL was significantly attenuated by PD98059, a specific p42/44 MAPK inhibitor. Conclusion These results indicate that the p42/44 MAPK pathway is an important regulator of mesangial cell proliferation and of renal functions.     

Expression of Monocyte Chemoattractant Protein-1 in Monocytes and Effects of Native and Oxidized Very Low Density Lipoproteins

Itiswellknownthattherearetwokindsoffoamcellsderivedfrommonocytemacrophagesandsmoothmusclecellsrespectivelyinatheroscleroticplaques.Thepenetrationandaccumulationofmonocytemacrophagesderivedfoamcellsunderanintactendotheliumisoneofearlylesions,thusinvestigationonmechanismformonocytemigratingintosubendothelialspacesisveryimportant.Previousstudieshaveshownthatendothelialcellsandsmoothmusclecellsincultureconstitutivelyexpressmonocytechemoattractantprotein1[l].Monocytechemoattractantprotein--1(MCP-l…     

植物血凝素样氧化型低密度脂蛋白受体介导氧化型低密度脂蛋白对内皮祖细胞存活和功能的影响

目的 研究植物血凝素样氧化型低密度脂蛋白受体（LOX—1）是否介导氧化型低密度脂蛋白（oxLDL）对内皮祖细胞（EPC）的存活及功能产生影响。方法 分选脐血CD34^＋细胞,培养于内皮细胞生长培养基（EGM-2）中。培养14d后,部分EPC与10、25、50μg/ml的oxLDL孵育48h;部分EPC先与LOX-1单克隆抗体（LOX—1mAb）预处理24h,再与50μg／ml oxLDL孵育48h;对照组不作处理。检测EPC存活率及EPC迁移、黏附和管状结构形成能力,并检测LOX-1的蛋白及mRNA表达。结果oxLDL浓度为25和50μg／ml时,凋亡率分别为（15．8±1．0）％和（18．8±2．0）％,显著高于对照组的（9．0±1．2）％（P〈0．05）;迁移率分别为（5．7±1．0）％和（5．1±0．8）％,显著低于对照组的（9．5±0．8）％,（P〈0．05）;黏附细胞数分别为（33±2）和（30±3）个,显著少于对照组的（37±5）个（P〈0．05）;形成的管状结构分别为（2．9±0．5）和（1．8±0．5）mm,显著短于对照组的（5．0±0．6）mm（P〈0．05）。OxLDL可增加LOX—1mRNA及蛋白的表达,oxLDL浓度为50μg／ml时,LOX—1mRNA表达由100％增加为（174±39）％,蛋白表达由100％增加为（172±8）％。OxLDL的上述作用能被LOX1mAb所阻断。结论OxLDL可降低EPC存活,抑制EPC功能,其作用是由LOX—1介导的。     

Physicochemical variations of malondialdehyde－and Cu~（2＋）－modified low density lipoprotein

Ｐｈｙｓｉｃｏｃｈｅｍｉｃａｌｖａｒｉａｔｉｏｎｓｏｆｍａｌｏｎｄｉａｌｄｅｈｙｄｅ－ａｎｄＣｕ~（２＋）－ｍｏｄｉｆｉｅｄｌｏｗｄｅｎｓｉｔｙｌｉｐｏｐｒｏｔｅｉｎＤｉｎｇＺｈｅｎｈｕａ（丁振华）；ＣｈｅｎＹｕａｎ（陈瑗）；ＺｈｏｕＭｅｉ（周玫）；?..     

非诺贝特对氧化型低密度脂蛋白诱导的脂肪细胞肿瘤坏死因子-α分泌的影响

目的 探讨调脂药物非诺贝特对兔脂肪细胞分泌肿瘤坏死因子-α（TNF-α）的影响及可能机制。方法 取新西兰兔皮下脂肪组织行脂肪细胞原代培养，分别给予不同浓度的氧化型低密度脂蛋白（OxLDL）及非诺贝特刺激。采用酶联免疫吸附法检测脂肪细胞培养液中TNF-α蛋白水平，半定量逆转录多聚酶链式反应测定脂肪细胞TNF-α和PPAR仅mRNA的表达。结果 较低剂量的OxLDL刺激脂肪细胞TNF-α分泌，呈剂量依赖性；不同浓度的非诺贝特呈剂量依赖性降低OxLDL诱导的脂肪细胞TNF-α分泌及mRANA表达，而相应的PPAR仅mRANA的表达则无显著变化。结论 非诺贝特可显著抑制OxLDL诱导的免脂肪细胞TNF-α分泌，这一作用可能有利于胰岛素抵抗的改善。     

低密度脂蛋白受体基因多态性对微粒化非诺贝特调脂疗效影 …

探讨低密度脂蛋白受体基因ＨｉｎｃⅡ酶切位点多态性对微粒化非贝特调脂疗效的影响。方法血清总胆固醇（ＴＣ）≥５．２０ｍｍｏｌ／Ｌ和／或甘油三酯（ＴＧ）２．００－５．６５ｍｍｏｌ／Ｌ之间得,共５２例,随机分为药物组３０例和安慰剂组２２例。     

脂康调节高脂血症家兔肝脏LDL-R mRNA水平的实验研究

目的通过建立新西兰家兔高脂血症模型，探讨肝脏低密度脂蛋白受体基因水平与高脂血症形成的关系。方法（1）建立高脂血症家兔模型；（2）应用原位杂交方法检测肝脏低密度脂蛋自受体基因水平。结果（1）成功建立高脂血症家兔模型；（2）脂康方剂可有效降低血脂水平，并能有效上调肝脏低密度脂蛋白受体基因水平。结论脂康方剂可激活肝脏细胞膜LDL—R基因表达，使LDL—R的活性增强，从而加速脂蛋白的分解，有效调节血脂水平。     

小而密低密度脂蛋白胆固醇对糖尿病足的影响

目的 分析2型糖尿病患者血清小而密低密度脂蛋白胆固醇（sdLDL-C）水平对糖尿病足的影响。方法 选取2018年6月—2019年6月在哈尔滨医科大学附属第一医院就诊的2型糖尿病患者213例,分为非糖尿病足组160例及糖尿病足组53例。收集患者基本临床资料,行生化检验及血清sdLDL-C检测,采用Logistic回归分析糖尿病足的相关危险因素。结果 糖尿病足组患者的收缩压（SBP）、空腹血糖（FBG）、糖化血红蛋白（HbA1c）、总胆固醇（TC）及sdLDL-C较非糖尿病足组升高（P <0.05）,视网膜病变率及大血管并发症率较非糖尿病足组高（P <0.05）,且糖尿病病程较长（P <0.05）。Logistic回归分析显示：FBG［O^R=3.302（95% CI：1.154,7.473）］、HbA1c［O^R=3.971（95% CI：1.982,6.131）］、sdLDL-C［O^R=5.996（95% CI：3.019,11.897）］是糖尿病足的危险因素。结论 血清sdLDL-C影响糖尿病足的发生、发展,可作为糖尿病足防治的潜在靶点。     

Effect of curcumin on the gene expression of low density lipoprotein receptors

Elevated level of low density lipoprotein-cho-lesterol(LDL-C)in plasma is one of the majorcauses for atherosclerosis and coronary heart dis-ease.3-hydroxy-3-methylglutaryl-coenzyme A(HMG-CoA)reductaseinhibitors,such as statins,alreadyin used clinically to reduce cholesterol lev-els,are effective in patients with atherosclerosis.They show a good safety profile in patients withhigh cholesterol levels and/or cardiovascular dis-ease,however,statins may be potentially associat-ed with developmen…     

糖尿病患者血清糖化低密度脂蛋白水平研究

目的研究糖尿病患者血清糖化低密度脂蛋白水平,为糖尿病并发冠心病的预防提供理论依据。方法选取我院收治的110例糖尿病患者作为观察组,选取同时期进行健康体检的健康者110例作为对照组,检测两组患者血清中的血糖、三酰甘油、载脂蛋白、胆固醇、糖化低密度脂蛋白、糖化血红蛋白等。结果观察组患者的GLDL水平明显高于对照组(P<0.05);但两组apo B100、LDL-C水平对比无统计学差异(P>0.05);apo A-Ⅰ与HDL-C的水平明显低于对照组(P<0.05);Clu、TG以及Chol水平明显高于对照组(P<0.05)。观察组的G-LDL水平与Glu呈正相关(r=0.631,P<0.05),与LDL-C、Hb A1c水平无相关关系(r=0.328、0.329,P>0.05)。结论糖尿病患者的血清糖化低密度脂蛋白水平显著提升,且与血糖值呈正相关关系。对评估糖尿病的治疗疗效有重要的临床价值。     

Effects of resveratrol on oxidative modification of human low density lipoprotein

Ｔｈｅｐｒｅｓｅｎｃｅｏｆｌｉｐｉｄ ｌａｄｅｎ“ｆｏａｍｃｅｌｌｓ”ｗｉｔｈｉｎｔｈｅｉｎｔｉｍａｏｆａｒｔｅｒｉｅｓｉｓａｃｈａｒａｃｔｅｒｉｓｔｉｃｆｅａｔｕｒｅｏｆａｔｈｅｒｏｓｃｌｅｒｏｔｉｃｌｅｓｉｏｎｓ Ｏｘｉｄａｔｉｖｅｌｙｍｏｄｉｆｉｅｄｌｏｗｄｅｎｓｉｔｙｌｉｐｏｐｒｏｔｅｉｎ (ＬＤＬ)ｉｓａｍａｊｏｒａｔｈｅｒｏｇｅｎｉｃｌｉｐｏｐｒｏｔｅｉｎｉｎｖｉｖｏ,ｗｈｉｃｈｉｓｔａｋｅｎｕｐｂｙｍａｃｒｏｐｈａｇｅｓｔｈｒｏｕｇｈｔｈｅｓｃａｖｅｎｇｅｒｒｅｃｅｐｔｏｒｐａｔｈｗａｙ…     

Effects of oxidized low density lipoprotein on the growth of human artery smooth muscle cells

Atherosclerosis(AS)isacommonandbasicpathologicalchangeofmanycardiovasculardiseases.1Amongtheriskfactorscontributingtohuman AS,oxidizedlowdensitylipoprotein(ox LDL)is consideredtostimulateASdirectlyandplaysanovelrole inthepathogenesisanddevelopmentofAS.2,3Despite proliferation,migrationandphenotypealterationof vascularsmoothmusclecells(vSMCs)arecritical changesinAS,4,5itisstillpoorlyunderstoodwhether ox LDLparticipatesinthepathologicalprocessof vSMCs.6WeisolatedandpurifiedhumanLDL,pro…     

辛伐他汀对人低密度脂蛋白氧化修饰影响的实验研究

目的研究辛伐他汀在体外对低密度脂蛋白氧化修饰的影响.方法以低密度脂蛋白氧化修饰为模型,以硫代巴比妥酸反应物质(TBARS)生成量及相对电泳迁移率(REM)为指标,研究了辛伐他汀对铜离子(Cu2 )诱导低密度脂蛋白氧化修饰的抑制作用.结果随辛伐他汀浓度从1～10μmol/L的增加,TBARS值分别减少67.3%,73.9%,81.9%,REM值减少48.3%,55.2%,58.6%,呈浓度及时间依赖关系.其中10μmol/L辛伐他汀可几乎完全抑制低密度脂蛋白氧化.结论辛伐他汀在体外能明显抑制Cu2 诱导的低密度脂蛋白氧化修饰.     

糖化低密度脂蛋白水平与冠脉粥样硬化程度的关系

目的 探讨糖化低密度脂蛋白(G-LDL)水平与冠脉粥样硬化程度的关系。方法 通过冠脉造影检查,选择糖尿病冠脉造影阴性(DM-NCHD)患者49例、糖尿病冠脉造影阳性(DM-CHD)患者50例及非糖尿病冠脉造影阴性(NC)患者50例。采用氯化硝基四氮唑蓝法检测DM-NCHD、DM-CHD及NC组的血清G-LDL水平。应用受试者工作特征曲线(ROC 曲线)评价血清G-LDL的诊断效能和最佳诊断分界值。结果 DM-NCHD组G-LDL水平低于DM-CHD组(P<0.05),高于NC组(P<0.05)。血清G-LDL水平为50.45时,灵敏度为0.80,特异度为0.84。DM-CHD组G-LDL水平与冠脉粥样硬化程度(用Gensini评分表示)呈正相关(r=0.638,P=0.001)。结论 DM-NCHD患者血清G-LDL水平明显低于DM-CHD患者,且G-LDL水平与冠脉粥样硬化程度呈正相关, G-LDL有望成为评价糖尿病患者冠脉粥样硬化风险的有效指标。     

Exploration of the Relationship between Phlegm-Dampness Constitution and Polymorphism of Low Density Lipoprotein Receptor Genes Pvu Ⅱ and Ava Ⅱ

Objective:To explore the polymorphism of low density lipoprotein receptor (LDL-R) genes PvuⅡand AvaⅡin a population with phlegm-dampness constitution (PDC).Methods: Polymorphism of LDL-R genes at PvuⅡand AvaⅡof 48 persons with gentle constitution (GC) and 61 with PDC were analyzed with PCR-RELP technique,and their serum contents of lipids and glucose were determined and compared as well.Results:The A allelic and P- allelic frequency were higher and the P allelic frequency was lower in subjects with PDC than those in subjects with GC,which were 0.3083 vs 0.1771,0.9098 vs 0.7708 and 0.0902 vs 0.2292,respectively,all showing significant difference between the two groups (P<0.05).Comparison of the two groups in serum levels of triglyceride (TG),fasting blood glucose,2 h postprandial blood glucose,and 2 h postprandial insulin showed that all the parameters were higher in subjects with PDC than in subjects with GC respectively, showing significant difference (P<0.05).Conclusion:PDC is related with the P- and A allelic frequency of higher LDL-R genes at PvuⅡand AvaⅡ,therefore,the polymorphism of LDL-R genes could be taken as one of the genetic markers for PDC,and humans with PDC are more liable to suffer from blood lipids and glucose disorder than those with GC.