The Hypolipidemic Activity of a Series of 2,3-Dihydrophthalazine-l,4-dione Derivatives in Rodents

A series of substituted 2,3-dihydrophthalazine-l,4-dione derivatives as well as the corresponding N,N-diaminophthalamides were prepared and were demonstrated to have potent hypolipidemic activity, lowering both serum triglyceride and cholesterol levels significantly at 20 mg/kg/day after 16 days of dosing in CF₁ male mice. The parent compound, 2,3-dihydrophthalazine-l,4-dione, lowered serum cholesterol 51% and serum triglyceride 43%. 2-(2-Carboxyethyl)-2,3-dihydrophthalazine-l,4-dione demonstrated the best hypocholesterolemic activity, with a 66% reduction after 16 days. The 2-(p-chlorophenyl) derivative demonstrated good activity (>40% reduction) in both screens, as did the 6-methyl-2,3-dihydrophthalazine-l,4-dione derivative. Of the amides, 4-methyk N,N-diaminophthalamide demonstrated the best hypolipidemic activity, affording a greater than 40% reduction. 2,3-Dihydrophthalazine-l,4-dione was found to inhibit the enzyme activity of acetyl CoA synthetase, ATP-dependent citrate lyase, sn-glycerol-3-phosphate acyl transferase, phosphatidylate phosphohydrolase, and mitochondrial citrate exchange of liver. In mice after 16 days of dosing, there was a reduction of cholesterol, triglycerides, neutral lipids, and phospholipids in the liver. Cholesterol and neutral lipids were reduced in rat chylomicrons, very low-density lipoproteins, and low-density lipoproteins. The cholesterol content of the high-density lipoprotein fraction was slightly elevated, but reductions in the triglycerides and phospholipids were observed in this lipoprotein fraction. ³H-Cholesterol distribution studies showed a lower concentration in the major organs and plasma, with a higher ³H-cholesterol content in the stomach and large intestine.     

The Hypolipidemic Activity of l-N-3-Methylphthalimido-butan-3-semicarbazone in Rodents

l-N-(3-Methylphthalimido)butan-3-one semicarbazone demonstrated potent hypolipidemic activity in normal rats and mice and hyperlipidemic diet-induced mice. The compound decreased tissue lipid levels and increased the fecal excretion of cholesterol and triglycerides. After 2 weeks of administration, serum lipoprotein levels were modulated so that very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) cholesterol concentrations were reduced and high-density lipoprotein (HDL) cholesterol concentrations were elevated to levels unprecedented by the cyclic imide derivatives previously tested. The VLDL triglyceride content was also reduced. Hepatic in vitro enzymatic studies demonstrated that the compound suppressed the activity of enzymes in the early synthesis of fatty acids and cholesterol and the regulatory enzymes for the de novo synthesis of triglycerides.     

苯妥英锌对家兔血清高密度脂蛋白胆固醇的影响

目的:研究家免口服苯妥英锌(PHTZ)对血清高密度脂蛋白胆固醇(HDL-C)的影响.方法:家兔分别口服PHTZ和苯妥英钠(PHTS)30d(剂量分别为:6,12,24mg·kg-1·d-1),用酶法测定血清中总胆固醇(TC)和三酰甘油(TG)的含量,HDL-C的测定采用磷钨酸镁盐沉淀后同TC测定法,低密度脂蛋白胆固醇(LDL-C)用费氏(Friedeuald)公式计算.用原子吸收分光光度法测定服药前后血清及服药后肝中Zn和Cu浓度.结果:PHTZ高、中剂量组分别使血清HDL-C升高76.0%(P＜0.01)和52.1%(P＜0.01),LDL-C分别降低19.7%(P＞0.05)和16.6%(P＞0.05),对TC和TG无显著影响.PHTZ使血清HDL-C升高的ED50为12.7mg·kg-1,PHTS使血清HDL-C提高的ED50为23.7mg·kg-1.PHTZ中剂量组使血清Zn浓度下降29.2%,与血清HDL-C上升的百分数呈负相关(r=-0.303 5,P＞0.05),使肝脏Zn浓度上升56.2%,与血清HDL-C上升的百分数呈正相关(r=0.726 3,P＜0.05),血清和肝脏中Cu无显著变化.结论:PHTZ使家兔血清HDL-C升高比PHTS更明显,ED50比PHTS低,可能与分子结构中的Zn有关.     

国产与进口阿托伐他汀治疗高脂血症的比较

目的:比较国产与进口阿托代他汀治疗高脂血症的疗效。方法:选择原发性高脂血症患者76例,随机分为国产阿托伐他汀(10mg·d~(-1))组和进口阿托伐他汀(10mg·d~(-1))组各38例,均治疗8周。结果:2组治疗4周时总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)均开始显著下降(P<0.01),治疗8周高密度脂蛋白胆固醇(HDL-C)开始显著上升(P<0.05),但2组间比较差异无显著意义(P>0.05);不良反应发生率国产组10.5％,进口组7.9％,2组差别无显著意义(P>0.05)。结论:国产阿托伐他汀与进口阿托伐他汀均有明显的调脂效果,两者使用均较安全。     

The Effects of N(4-Methylphenyl)diphenimide on Lipid Metabolism of Sprague Dawley Rats

N(4-Methylphenyl)diphenimide proved to be an effective hypolipidemic agent in rats at 10 and 20 mg/kg/day. Both serum cholesterol and triglyceride levels were reduced significantly. Decreases in tissue lipids as well as VLDL cholesterol levels were observed. HDL-cholesterol was elevated even at 10 mg/kg/day. The agent was equally effective in hyperlipidemic diet-induced rats, lowering serum lipids and VLDL- and LDL-cholesterol while elevating HDL-cholesterol levels. The drug interfered with the incorporation of ³H-cholesterol and ³H-palmitic acid into chylomicrons, VLDL, and LDL. The two precursors were incorporated at a higher rate into HDL.³H-Leucine was incorporated into chylomicrons, VLDL, and LDL at a higher rate, but not into HDL. Reduced uptake of the precursor for lipid synthesis was noted in tissues after treatment with the drug.     

2-(4-氯-3-甲基苯基)-1,2,4-三嗪-3,5(2H,4H)-二酮的合成

对硝基邻甲苯胺经重氮化、氯代、还原、闭环、水解、脱羧6步反应得到2-（4-氯-3-甲基苯基）-1,2,4-三嗪-3,5（2H,4H）-二酮,总收率约40%。     

Effect of gender,dose, and time on 3-(3,5-dichlorophenyl)-2,4-thiazolidinedione (DCPT)-induced hepatotoxicity in Fischer 344 rats

1.?The thiazolidinedione ring present in drugs available for type II diabetes can contribute to hepatic injury. Another thiazolidinedione ring-containing compound, 3-(3,5-dichlorophenyl)-2,4-thiazoli-dinedione (DCPT), produces liver damage in rats. Accordingly, the effects of gender, dose, and time on DCPT hepatotoxicity were therefore evaluated.

2.?Male rats were more sensitive to DCPT (0.4–1.0 mmol kg^?1 by intraperitoneal administration) as shown by increased serum alanine aminotransferase levels and altered hepatic morphology 24 h post-dosing. Effects in both genders were dose dependent. In males, DCPT (0.6 mmol kg^?1) produced elevations in alanine aminotransferases and changes in liver h after dosing that progressively worsened up to 12 h. DCPT-induced renal effects were mild.

3.?It is concluded that male rats are more susceptible to DCPT hepatotoxicity and that damage occurs rapidly. DCPT primarily affects the liver and can be a useful compound to investigate the role of the thiazolidinedione ring in hepatic injury. However, the gender dependency and rapid onset of DCPT hepatotoxicity require further investigation.     

Effect of ezetimibe monotherapy on the concentration of lipoprotein subfractions in patients with primary dyslipidaemia

ABSTRACT

Background: Recent studies suggest that the distribution of lipoprotein subfractions is an independent predictor of vascular events. Therefore, we evaluated the effect of ezetimibe (a selective cholesterol transport inhibitor) on the concentrations of lipoprotein subfractions in patients with primary dyslipidaemia.

Materials and methods: Patients (n = 50) with primary dyslipidaemias were recruited. The concentrations of the individual lipoprotein subfractions were measured using the Lipoprint system at baseline and after 16 weeks of treatment.

Results: Ezetimibe reduced total, low-density lipoprotein cholesterol (LDL?C) and non-high-density lipoprotein cholesterol (HDL?C) values as well as apolipoprotein B concentrations. Subfractionation of apolipoprotein B-containing lipoproteins showed that the reduction in LDL?C values was due to a fall in the concentrations of all LDL subfractions. However, a more pronounced trend towards a decrease in the concen­trations of dense LDL subfractions was observed. Patients with triglyceride values >1.7?mmol/L had significantly greater reductions in the concentrations of small, dense LDL particles compared with those with normal triglyceride levels (49 vs. 19%, respectively; p < 0.05). Ezetimibe decreased the concentrations of HDL?C mainly due to a fall in the concentration of dense HDL subfractions.

Conclusion: Ezetimibe can favourably affect the distribution of LDL subfractions, especially in patients with elevated triglyceride values. Further studies are needed to clarify the significance of the ezetimibe-induced reduction in the concentrations of dense HDL particles.     

Role of biotransformation in 3-(3,5-dichlorophenyl)-2,4-thiazolidinedione-induced hepatotoxicity in Fischer 344 rats

Cytochrome P450 (CYP)-mediated metabolism in the thiazolidinedione (TZD) ring may contribute to the hepatotoxicity of the insulin-sensitizing agents such as troglitazone. We were interested in determining if biotransformation could also be a factor in the liver damage associated with another TZD ring containing compound, 3-(3,5-dichlorophenyl)-2,4-thiazolidinedione (DCPT). Therefore, hepatotoxic doses of DCPT (0.6 or 1.0mmol/kg, i.p.) were administered to male Fischer 344 rats after pretreatment with vehicle, 1-aminobenzotriazole (ABT, non-selective CYP inhibitor) and troleandomycin (TAO, CYP3A inhibitor). Alternatively, rats were pretreated with vehicle or the CYP3A inducer dexamethasone (DEX) prior to a non-toxic DCPT dose (0.2mmol/kg, i.p.). Vehicle-, ABT-, TAO- and DEX-only control groups were also run. Toxicity was assessed 24h after DCPT administration. Both hepatotoxic doses of DCPT induced elevations in serum alanine aminotransferase (ALT) levels that were attenuated by ABT or TAO pretreatment. Liver sections from rats that received vehicle+DCPT revealed areas of gross necrosis and neutrophil invasion, whereas sections from ABT+DCPT and TAO+DCPT rats showed minor changes compared to controls. DEX pretreatment potentiated ALT levels associated with the non-toxic DCPT dose. Furthermore, DEX+DCPT rat liver sections exhibited hepatic injury when compared against rats that received vehicle+DCPT. Blood urea nitrogen levels, urinalysis and kidney morphology were not markedly altered by any combination of pretreatments or treatments. Enzyme activity and Western blotting experiments with rat liver microsomes confirmed the effects of the various pretreatments. Our results suggest that hepatic CYP3A isozymes may be involved in DCPT-induced liver damage in male rats. We believe this is the first report demonstrating that modulation of the biotransformation of a TZD ring-containing compound can alter hepatotoxicity in a common animal model.     

Synthesis of imidazolidine-2,4-dione and 2-thioxoimidazolidin-4-one derivatives as inhibitors of virulence factors production in Pseudomonas aeruginosa

In an attempt to counteract bacterial pathogenicity, a set of novel imidazolidine-2,4-dione and 2-thioxoimidazolidin-4-one derivatives was synthesized and evaluated as inhibitors of bacterial virulence. The new compounds were characterized and screened for their effects on the expression of virulence factors of Pseudomonas aeruginosa, including protease, hemolysin, and pyocyanin. Imidazolidine-2,4-diones 4c , 4j , and 12a showed complete inhibition of the protease enzyme, and they almost completely inhibited the production of hemolysin at 1/4 MIC (1/4 minimum inhibitory concentration; 1, 0.5, and 0.5 mg/ml, respectively). 2-Thioxoimidazolidin-4-one derivative 7a exhibited the best inhibitory activity (96.4%) against pyocyanin production at 1 mg/ml (1/4 MIC). A docking study was preformed to explore the potential binding interactions with quorum-sensing receptors (LasR and RhlR), which are responsible for the expression of virulence genes.     

Effects of ezetimibe,either alone or in combination with atorvastatin,on serum visfatin levels: a pilot study

Introduction: Ezetimibe inhibits intestinal absorption of cholesterol and lowers circulating low-density lipoprotein cholesterol levels. Visfatin is a novel adipokine, which may be implicated in the atherosclerotic process. Objective: The aim of this study was to explore the possible association between ezetimibe administration and serum visfatin concentrations. Methods: Patients (n = 30) with primary dyslipidemia and another 30 who failed to reach their assigned low-density lipoprotein cholesterol target on atorvastatin therapy (20 mg/day) were included in the study. All participants were given ezetimibe at 10 mg/day for 12 weeks. Results: At baseline the visfatin levels correlated significantly with the total cholesterol (r = 0.61 and p < 0.01) and low-density lipoprotein cholesterol (r = 0.51 and p < 0.01) levels in the statin pretreatment group. Furthermore, in the statin group the post-treatment levels of visfatin and low-density lipoprotein cholesterol were significantly correlated (r = 0.57 and p < 0.01). The serum visfatin concentrations did not change significantly in either the monotherapy or statin pretreatment groups or in subgroups divided according to the baseline lipid variables. In both the ezetimibe monotherapy and ezetimibe plus atorvastatin groups the effect of ezetimibe on the lipid variables depended on the baseline lipid values. The low-density lipoprotein cholesterol:high density lipoprotein cholesterol ratio was consistently improved by ezetimibe in all groups or subgroups. Conclusions: Ezetimibe did not alter serum visfatin concentrations, either when administered as monotherapy or combined with a statin. Future studies investigating the effect of ezetimibe on visfatin levels need to include groups of patients with distinct lipid characteristics.     

脂蛋白（a）在动脉粥样硬化患者中的变化及血脂康干预的影响

目的：探讨冠心病（CHD）患者及脑梗死患者血清脂蛋白（a）[Lp(a)]水平及药物干预的影响。方法：151例CHD病人，其中急民生心肌梗死（AMI）20例，陈旧性心肌梗死（OMI）49例，心绞痛（AP）82例；脑梗死患者42例及正常对照组30例，测定其血清Lp(a)浓度。对高Lp(a）水平随机分组用血脂康胶囊及维生素C治疗。结果：CHD及脑梗死组其血清Lp(a)水平明显高于对照组（均P＜0.01)；CHD组高于脑梗死组（P＜0.01)。CHD组中，AMI组＞AP组＞OMI组（P＜0.01或P＜0.05）。用血脂康胶囊4粒/日治疗40例，12周末血清Lp(a)下降19.66%，与治疗前比较差异显著（P＜0.05)。结论：提示Lp(a)有致动脉粥样硬化的作用；血脂康胶囊对高血清Lp(a)水平安全有效。     

Hypolipidemic Activity of o-(N-Phthalimido)acetophenone in Sprague Dawley Rats

o-(N-Phthalimido)acetophenone has proven to be an effective hypolipidemic agent in rats at 20 mg/kg/ day orally. The agent suppressed the activity of the rate-limiting enzyme of the liver involved in de novo synthesis of triglycerides. The synthetic rate-limiting enzyme for cholesterol esters was also inhibited by the drug in vivo. o-(N-Phthalimido)acetophenone lowered cholesterol in the liver and the aorta wall and generally caused an increase in phospholipids in body tissues. Serum lipoproteins were modulated by the drug with a decrease in cholesterol and triglycerides in the chylomicron, very low-density lipoproteins (VLDL), and low-density lipoproteins (LDL) and an increase in high-density lipoprotein (HDL) cholesterol. The phospholipid content was increased in the chylomicron, VLDL, and LDL fractions. In hyperlipidemic rats, o-(N-phthalimido)acetophenone lowered elevated blood lipid levels at 20 mg/kg/day orally after 3 weeks of administration. The hypolipidemic rat after drug treatment had a lower LDL cholesterol and a higher HDL cholesterol content, which is therapeutically desirable to protect against cardiovascular disease.     

用交叉双盲法观察潘生丁对高脂血症的影响

用交叉双盲法观察潘生丁对43例门诊高脂血症病人血清甘油三酯,胆固醇和高密度脂蛋白胆固醇含量的作用。总疗程6mo,3mo时安慰剂与药物进行双盲交叉。结果显示潘生丁有降低血清胆固醇含量的作用,对血清甘油三酯和高密度脂蛋白胆固醇作用不明显。     

Design,synthesis, molecular docking,and anticancer evaluations of 1-benzylquinazoline-2,4(1H,3H)-dione bearing different moieties as VEGFR-2 inhibitors

A novel series of 1-benzylquinazoline-2,4(1H,3H)-dione derivatives, 6a , b to 11a – e , was designed, synthesized, and evaluated for their anticancer activity against HepG2, HCT-116, and MCF-7 cells. Compounds 11b , 11e , and 11c were found to be the most potent derivatives of all tested compounds against the HepG2, HCT-116, and MCF-7 cancer cell lines, with GI₅₀ = 9.16 ± 0.8, 5.69 ± 0.4, 5.27 ± 0.2 µM, 9.32 ± 0.9, 6.37 ± 0.7, 5.67 ± 0.5 µM, and 9.39 ± 0.5, 6.87 ± 0.7, 5.80 ± 0.4 µM, respectively. These compounds exhibited nearly the same activity as sorafenib against HepG2 and HCT-116 cells and a higher activity against MCF-7 cells (GI₅₀ = 9.18 ± 0.6, 5.47 ± 0.3, and 7.26 ± 0.3 µM, respectively). Also, these compounds displayed a lower activity than doxorubicin against HepG2 cells and a higher activity against HCT-116 and MCF-7 cells (GI₅₀ = 7.94 ± 0.6, 8.07 ± 0.8, and 6.75 ± 0.4 µM, respectively). The most active antiproliferative derivatives, 6a , b , 8 , 9 , and 11a – e , were selected to evaluate their enzymatic inhibitory activity against VEGFR-2. Compounds 11b , 11e , and 11c potently inhibited VEGFR-2 at IC₅₀ values of 0.12 ± 0.02, 0.12 ± 0.02, and 0.13 ± 0.02 µM, respectively, which are nearly equipotent as sorafenib IC₅₀ value (0.10 ± 0.02 µM). Furthermore, molecular docking studies were performed for all synthesized compounds to assess their binding pattern and affinity toward the VEGFR-2 active site.     

Effect of structural modifications on 3-(3,5-dichlorophenyl)-2,4-thiazolidinedione-induced hepatotoxicity in Fischer 344 rats

Glitazones, used for type II diabetes, have been associated with liver damage in humans. A structural feature known as a 2,4‐thiazolidinedione (TZD) ring may contribute to this toxicity. TZD rings are of interest since continued human exposure via the glitazones and various prototype drugs is possible. Previously, we found that 3‐(3,5‐dichlorophenyl)‐2,4‐thiazolidinedione (DCPT) was hepatotoxic in rats. To evaluate the importance of structure on DCPT toxicity, we therefore studied two series of analogs. The TZD ring was replaced with: a mercaptoacetic acid group {[[[(3,5‐dichlorophenyl)amino]carbonyl]thio]acetic acid, DCTA}; a methylated TZD ring [3‐(3,5‐dichlorophenyl)‐5‐methyl‐2,4‐thiazolidinedione, DPMT]; and isomeric thiazolidinone rings [3‐(3,5‐dichlorophenyl)‐2‐ and 3‐(3,5‐dichlorophenyl)‐4‐thiazolidinone, 2‐DCTD and 4‐DCTD, respectively]. The following phenyl ring‐modified analogs were also tested: 3‐phenyl‐, 3‐(4‐chlorophenyl)‐, 3‐(3,5‐dimethylphenyl)‐ and 3‐[3,5‐bis(trifluoromethyl)phenyl]‐2,4‐thiazolidinedione (PTZD, CPTD, DMPT and DFMPT, respectively). Toxicity was assessed in male Fischer 344 rats 24 h after administration of the compounds. In the TZD series only DPMT produced liver damage, as evidenced by elevated serum alanine aminotransferase (ALT) activities at 0.6 and 1.0 mmol kg^?1 (298.6 ± 176.1 and 327.3 ± 102.9 Sigma‐Frankel units ml^?1, respectively) vs corn oil controls (36.0 ± 11.3) and morphological changes in liver sections. Among the phenyl analogs, hepatotoxicity was observed in rats administered PTZD, CPTD and DMPT; with ALT values of 1196.2 ± 133.6, 1622.5 ± 218.5 and 2071.9 ± 217.8, respectively (1.0 mmol kg^?1 doses). Morphological examination revealed severe hepatic necrosis in these animals. Our results suggest that hepatotoxicity of these compounds is critically dependent on the presence of a TZD ring and also the phenyl substituents. Copyright © 2011 John Wiley & Sons, Ltd.     

新型PI3K抑制剂邻苯二甲酰亚胺及其衍生物的设计合成与抗肿瘤活性

目的设计合成新的磷脂酰肌醇3-激酶抑制剂,并测定其体外活性。方法通过结构替换、分子对接技术设计一系列邻苯二甲酰亚胺类化合物。以4-溴邻苯二甲酸酐为原料经胺解反应得到N-芳基-4-溴邻苯二甲酰亚胺Ⅰ1～Ⅰ8;Ⅰ1～Ⅰ8再与3-(4-氟苯磺酰胺基)苯硼酸经Suzuki偶联得到N-芳基-4-(3-对氟苯磺酰胺苯基)邻苯二甲酰亚胺Ⅲ1～Ⅲ8;以阿霉素为阳性对照,采用MTT法进行体外活性测定。结果与结论合成了16个未见文献报道的邻苯二甲酰亚胺类化合物,目标化合物的结构经1H-NMR、MS谱确证;体外活性实验结果显示,N-芳基-4-(3-对氟苯磺酰胺苯基)邻苯二甲酰亚胺衍生物具有潜在的抑制肿瘤生长作用,其中,化合物Ⅲ1对A549、MCF-7肿瘤细胞表现出显著的抑制活性,具有进一步研究的价值。     

氧化低密度脂蛋白致血管内皮损伤机制及中药复方防治的研究进展

低密度脂蛋白经氧化修饰后主要通过凝集素样氧化低密度脂蛋白受体-1导致管内皮细胞损伤,诱导黏附分子和炎症因子的合成与释放,加重血管炎症反应,诱导内皮细胞凋亡,进而导致动脉粥样硬化等心血管疾病.中药复方通过抑制低密度脂蛋白(LDL)氧化生成氧化低密度脂蛋白(OX-LDL),防治血管内皮损伤,进而防治动脉粥样硬化的发生与发展...     

Tyrosinemia produced by 2-(2-nitro-4-trifluoromethylbenzoyl)-cyclohexane-1,3-dione (NTBC) in experimental animals and its relationship to corneal injury

2-(2-Nitro-4-trifluoromethylbenzoyl)-cyclohexane-1,3-dione (NTBC) is a potent inhibitor of rat liver 4-hydroxyphenylpyruvate dioxygenase (HPPD) leading to tyrosinemia and corneal opacity. We examined the effect of NTBC on the extent of tyrosinemia and production of corneal lesions in the beagle dog, rabbit and rhesus monkey, as part of safety evaluation on this drug. A single oral dose of 10 mg NTBC/kg to beagle dogs or rabbits increased the concentration of tyrosine in plasma and aqueous humour of the eye, the tyrosinemia being both time- and dose-dependent. Hepatic HPPD was markedly inhibited with little effect on the activity of tyrosine aminotransferase (TAT) and homogentisic acid oxidase at the time of peak plasma tyrosine. Daily oral administration of NTBC to beagle dogs at 0.1, 0.5, 1.5 and 5 mg/kg/day produced corneal opacities with an incidence of 34% following 11 weeks of dosing, which reversed upon withdrawal of the drug. Tyrosine in plasma and aqueous humour was increased at all dose levels, 18 weeks after dosing. In contrast, daily oral administration of NTBC to rabbits for 6 weeks and rhesus monkeys for 12 weeks at 10 mg/kg/day produced no evidence of corneal opacities although tyrosine values were markedly increased. Our studies have shown that NTBC is a potent inhibitor of rabbit, beagle dog and by inference rhesus monkey liver HPPD producing a marked tyrosinemia in all species studied, while only beagle dogs show corneal lesions. The production of corneal lesions in experimental animals exposed to NTBC does not appear to be simply related to the concentration of tyrosine in ocular fluid, other as yet unidentified factors appear to be necessary to trigger tissue injury.     

高密度脂蛋白组成部分中的不同亚类对冠状动脉狭窄程度影响的相关性研究

目的：探讨冠脉造影患者高密度脂蛋白（high-density lipoprotein,HDL）亚类对冠状动脉狭窄程度影响的相关性。方法（1）抽取2013—2014年因疑诊冠心病（coronary heart disease,CHD）入住该院老年医学科、心内科行冠状动脉造影（coronary arteriography,CAG）的患者122例,经选择性冠状动脉造影确诊为CHD患者（至少有一支冠状动脉或分支狭窄＞50％）96例,其中男62例,女34例,平均年龄（60．31±8．72）岁,未诊断CHD患者26例,男10例,女16例,平均年龄（59．00±13．51）岁;（2）抽取患者空腹12 h静脉血,选择双向电泳—免疫印迹检测法24 h内测定HDL亚类,对患者冠脉造影结果（采用Gensini评分）评价冠状动脉狭窄程度;（3）计量资料用均数±标准差（x ±s）表示,定性资料用χ2检验,两组比较采用独立样本的t检验, Logisitic回归分析检验与冠心病相关因素,两因素相关性采用线性相关分析。结果（1）单因素卡方、两样本独立t检验显示性别、吸烟史、糖尿病史、收缩压、体质指数（body mass index,BMI）、腰围（waist circumference,WC）、腰臀比（waist to hip ratio, WHR）、HDL、LDL、ApoA-I 、Lpa、Preβ1-HDL、HDL3b、HDL3c、HDL2b与冠心病有关,差异有统计学意义（P＜0．05）;（2）TG、Preβ1-HDL、HDL3b是冠心病危险因素,HDL2b是冠心病保护因素（P＜0．05）;（3）HDL2b与Gensini评分结果成负相关,Preβ1-HDL、HDL3b与Gensini评分结果成正相关。结论在临床诊断治疗中,HDL2b值有可能做为冠心病预测因素,Preβ1-HDL、HDL3b值可为预测和诊断CHD提供重要依据,冠心病的防治不仅要改善和促进胆固醇逆转运还要调节血脂,调整HDL亚类的构成比。