聚合酶链反应-单链构象多态性分析在家族性高胆固醇血症研究中的应用

目的：探讨聚合酶链反应－单链构象多态性分析（polymerase chain reaction-single strand conformation polymorphism，PCR－SSCP）在家族性高胆固醇血症（familial hypercholesterolemia,FH)研究中的应用价值。方法：提取FH患者外周血基因组DNA，进行PCR－SSCP及DNA序列分析。结果：对1家2例临床诊断为FH的患儿及其父母从基因水平明确了诊断。LDL受体基因突变是位于第6外显子的移框突变，结论：PCR－SSCCP可以从基因水平对FH患者明确诊断，并可对先证者家族系成员早期诊断，以便提供咨询和指导。     

Hyperlipidemia disrupts cerebrovascular reflexes and worsens ischemic perfusion defect

Hyperlipidemia is a highly prevalent risk factor for coronary and cervical atherosclerosis and stroke. However, even in the absence of overt atherosclerosis, hyperlipidemia disrupts endothelial and smooth muscle function. We investigated the impact of hyperlipidemia on resting-brain perfusion, fundamental cerebrovascular reflexes, and dynamic perfusion defect during acute focal ischemia in hyperlipidemic apolipoprotein E knockout mice before the development of flow-limiting atherosclerotic stenoses. Despite elevated blood pressures, absolute resting cerebral blood flow was reduced by 20% in apolipoprotein E knockout compared with wild type when measured by [¹⁴C]-iodoamphetamine technique. Noninvasive, high spatiotemporal resolution laser speckle flow imaging revealed that the lower autoregulatory limit was elevated in apolipoprotein E knockout mice (60 vs. 40 mm Hg), and cortical hyperemic responses to hypercapnia and functional activation were attenuated by 30% and 64%, respectively. Distal middle cerebral artery occlusion caused significantly larger perfusion defects and infarct volumes in apolipoprotein E knockout compared with wild type. Cerebrovascular dysfunction showed a direct relationship to the duration of high-fat diet. These data suggest that hyperlipidemia disrupts cerebral blood flow regulation and diminishes collateral perfusion in acute stroke in the absence of hemodynamically significant atherosclerosis.     

Different inflammatory responses induced by three LDL‐lowering apheresis columns

Low‐density lipoprotein (LDL) apheresis is well‐established in selected patients with uncontrolled LDL levels. As such treatment affects biomarkers important in atherosclerosis and acute coronary syndromes, we systematically compared the inflammatory response induced by three LDL apheresis columns. Three patients with heterozygous familial hypercholesterolemia participated in a cross‐over study with six consecutive treatments with three different LDL apheresis columns: DL‐75 (whole blood adsorption), LA‐15 (plasma adsorption), and EC‐50W (plasma filtration). Biochemical parameters and inflammatory biomarkers, including complement activation products and 27 cytokines, chemokines, and growth factors were measured before and after treatment. Complement was activated through the alternative pathway. The final end product sC5b‐9 increased significantly (P < 0.01) and equally with all devices, whereas the anaphylatoxins C3a and C5a were lower by use of the adsorption columns. Hs‐CRP was reduced by 77% (DL‐75), 72% (LA‐15), and 43% (EC‐50W). The cytokines were consistently either increased (IL‐1ra, IP‐10, MCP‐1), decreased (IFN‐γ, TNF‐α, RANTES, PDGF, VEGF), or hardly changed (including IL‐6, IL8, MIP‐1αβ) during treatment. The changes were in general less pronounced with the adsorption columns. All columns reduced LDL significantly and to the same extent. In conclusion, three LDL‐apheresis devices with equal cholesterol‐lowering effect differed significantly with respect to the inflammatory response. J. Clin. Apheresis, 2009. © 2009 Wiley‐Liss, Inc.     

P选择素在高胆固醇血症小鼠肾脏的表达

目的:研究P选择素在高胆固醇血症小鼠肾脏的表达,探讨脂质肾毒性损伤的机制。方法:24只雌性C57/BL小鼠分为2组,普通膳食组(A组)和高胆固醇膳食组(B组),喂养15周,用生化酶法检测血脂;用PAS和HE染色观察肾脏组织学改变;免疫组化SABC法检测P选择素的表达。结果:B组血清总胆固醇(Tch)和低密度脂蛋白胆固醇(LDL-C)浓度显著高于A组(P<0.05,P<0.01);肾小球细胞数及系膜区占肾小球面积比显著高于A组(P<0.05,P<0.01);P选择素表达明显增加(P<0.01)。结论:P选择素的明显表达可能与脂质引起的肾小管间质损害有关。     

Treatment of hypercholesterolemia in children and adolescents

In patients with severe genetic hypercholesterolemia, therapeutic reduction of elevated serum total cholesterol and LDL cholesterol should begin in early childhood to lower the risks of cardiovascular disease later in life. We evaluated the effects of outpatient therapy with diet alone and with combined diet and drug therapy in children and adolescents with hypercholesterolemia of apparent dominant inheritance. Serum lipid values before and during dietary treatment were available in 35 patients (mean age at start of treatment 7.9 years, range 2.0-17.6 years) followed for an average duration of 17.5 months (range 4-70 months). A comparison between untreated state and combined therapy with diet and cholestyramine was possible in 14 patients (mean age 8.6 years, range 2.4-17.0 years) followed for 27.9 months (range 4-97 months). Dietary modification achieved by repeated counseling and training lowered serum total cholesterol by mean (+/- SE) 11.7 +/- 1.9% (p < 0.0001) and LDL cholesterol by 17.3 +/- 3.5% (p < 0.0001). However, five of 35 patients did not show an appreciable effect of therapy (cholesterol reduction < 5%), possibly because of non-compliance. Diet combined with cholestyramine in an average dose of 0.36 g/kg body weight/day reduced total cholesterol by 33.0 +/- 2.4% (p < 0.0001) and LDL cholesterol by 37.5 +/- 4.3% (p < 0.0001) and was effective in all patients. Both forms of treatment had no effect on serum triglycerides and HLD cholesterol. No serious side effects were noted, and percentile values for weight and height remained unchanged in all but three obese children.(ABSTRACT TRUNCATED AT 250 WORDS)     

蘑菇片治疗人体高血脂的效果观察

采用蘑菇片剂对摄取一般膳食和高营养膳食的高血脂患者进行降血脂效果观察,治疗期为3个月。结果表明,血清胆固醇和甘油三酯浓度平均值明显下降,摄取一般膳食的高血脂患者,血清胆固醇浓度平均下降59.5mg％(P<0.05),甘油三酯浓度平均下降175.5mg％(P<0.05)。降血脂的有效率为90.0％。摄取高营养膳食患者,血清胆固醇浓度下降42.4mg％(P<0.01),甘油三酯浓度下降15.4mg％,血清HDL-C/LDL-C比值从0.46升高至0.59,TC/HDL-C比值从4.12下降到3.57。治疗三个月后,总的治愈率为64.7％。     

The efficacy of dietary intervention alone or combined with hormone replacement therapy in postmenopausal women with hypercholesterolemia in Seoul,Korea

Summary Background Women have an increased incidence of cardiovascular disease (CVD) due to hormone imbalance-induced changes in blood lipid profiles after menopause. Aim of study This study was done to compare the effects of dietary intervention and hormone replacement therapy, alone or in combination, on blood lipids and body weight in Korean postmenopausal women with hypercholesterolemia. Method The subjects were treated by one of three different treatments for 12 weeks: hormone replacement therapy (HRT group, n = 8), dietary intervention (DIET group, n = 8) and hormone replacement therapy combined with dietary intervention (HRT+DIET group, n = 8). Results Serum TC and LDL-C levels decreased by 13–16 % and 24–28 % in the HRT group, by 17–19 % and 21–23 % in the DIET group and by 19–26 % and 32–39 % in the HRT+DIET group, respectively (P < 0.05). Serum HDL-C levels decreased in the DIET group (−6.4 %, P < 0.05) but not in the HRT and HRT+DIET groups. Serum TG levels increased in the HRT group (18 %, P < 0.05) but decreased in the DIET group (−24.4 %, P < 0.05). In the HRT+ DIET group, serum TG levels did not change. Body weight decreased only in the DIET group. Conclusions We can conclude that dietary intervention produces a considerable improvement in blood lipid profiles and body weight, even though our study is limited by the sample size. Thus, the treatment to reduce risk of CVD should be individualized on the basis of the patient's dietary intake status, and at least, HRT should not be substituted for dietary intervention. Received: 16 July 2001, Accepted: 18 February 2002     

血脂康与辛伐他汀治疗原发性高脂血症的对比研究

目的比较中药血脂康、辛伐他汀(舒降之)治疗原发性高脂血症的调脂作用和安全性。方法80例原发性高脂血症患者随机分为血脂康组和舒降之组,各服药8周为1个疗程,治疗期间患者保持治疗前的饮食习惯,不用其他干扰血脂代谢的药物。8周后观察两组调脂效果和不良反应。结果血脂康组:TC降低25.15%,TG降低21.22%,DL-C降低38.08%,TC-HDL-C/HDL-C降低44.03%。舒降之组:TC降低26.02%,TG降低22.62%,LDL-C降低38.50%,TC-HDL-C/HDL-C降低44.22%,两组各项指标治疗后的组内相比,均有统计学意义(P<0.001),两组间各项指标治疗后对应比较均无统计学意义(P>0.05),两组间不良反应轻微,不影响继续治疗,不良反应总发生率血脂康组较低(P<0.05)。结论血脂康和辛伐他汀均有强大的降低TC、TG、LDL-C和TC-HDL-C/HDL-C的作用,均为治疗原发性高脂血症有效和安全的药物,血脂康不良反应更低,提示中药血脂康具有更好的耐受性。     

大豆异黄酮改善高血脂小鼠记忆的研究

目的:探讨大豆异黄酮(SI)对高血脂小鼠记忆的影响及有关机制。方法:将小鼠分为4组,基础饲料对照组;高脂饲料对照组;低剂量SI组:高脂饲料+SI(50mg/kgbw);高剂量SI组:高脂饲料+SI(100mg/kgbw)。连续灌胃SI30d后,测定小鼠记忆能力,并检测血清总胆固醇(TC)、甘油三酯(TG)和β-脂蛋白含量及超氧化物歧化酶(SOD)活力,血液、大脑皮质和海马中胆碱酯酶(AChE)活性以及大脑皮质和海马中氨基酸神经递质(Asp、Glu和Gly)含量。结果:在实验期内造成高脂模型,与对照组比较,高血脂小鼠记忆明显降低,而SI明显改善高血脂小鼠记忆能力,同时使小鼠血清中TC、TG和β-脂蛋白含量以及大脑皮质和海马中AChE活力显著降低,而血清SOD活力及大脑皮质和海马中氨基酸神经递质含量显著提高。结论:SI可改善高血脂小鼠的记忆,其机制可能与其抗氧化作用及调节神经递质的代谢有关。