Lipids,lipid-lowering drug and sepsis:a Mendelian randomization study

lipid-lowering interventions on the disease.Methods:Two-sample Mendelian randomization analyses were conducted to evaluate the associations of high-density lipoprotein cholesterol,low-density lipoprotein cholesterol,triglycerides,apolipoprotein B and apolipoprotein A-I levels with risks for sepsis,and those of low-density lipoprotein cholesterol(HMGCR,PCSK9,NPC1L1),triglycerides(LPL,ANGPTL3,APOC3)and high-density lipoprotein cholesterol(CETP),apolipoprotein A-I(CETP),apolipoprotein B(HMGCR,PCSK9,NPC1L1,LPL,APOC3)with sepsis.Results:HMGCR-mediated low-density lipoprotein cholesterol and apolipoprotein B were associated with an increased risk of sepsis,with an odds ratio value of 1.4(95%confidence interval(CI):1.06-1.84,P=0.017)and 1.41(95%CI:1.01-1.98,P=0.046).CETP-mediated high-density lipoprotein cholesterol and apolipoprotein A-I were associated with a reduced risk of sepsis,with an odds ratio of 0.87(95%CI:0.82-0.92,P<0.01)respectively and 0.84(95%CI:0.78-0.9,P<0.01).Sensitivity analysis showed that the results were robust.Conclusion:HMG-CoA reductase inhibitors and CETP inhibitors may contribute to the prevention and treatment of sepsis.

Role of lipid-lowering agents in the management of diabetic retinopathy

Diabetic retinopathy affects a substantial proportion of patients with diabetes mellitus(DM) and is the leading cause of blindness in working-aged adults. Even though the incidence of diabetic retinopathy has declined in the last decades, its prevalence increased and is expected to rise further as a result of the increasing incidence of type 2 DM(T2DM) and the longer life expectancy of patients with DM. The pathogenesis of diabetic retinopathy is multifactorial. Some observational studies suggested an association between dyslipidemia and the development and progression of retinopathy in patients with DM but others did not confirm this association. Regarding lipid-lowering agents, studies that evaluated the role of statins in the management of these patients are mostly small and yielded discrepant results. Large randomized studies with statins in patients with T2DM showed no benefit of these agents on diabetic retinopathy but were not designed to address this effect. In contrast, both preclinical data and two large randomized controlled studies, the FIELD and the ACCORD trial, showed that fenofibrate delays the progression of diabetic retinopathy. Even though the mechanisms underpinning this favorable effect are not entirely clear, these findings suggest that fenofibrate might represent a useful tool for the management of diabetic retinopathy.

Effects of lipid-lowering agents on diabetic retinopathy: a Meta-analysis and systematic review

AIM：To clarify this controversy and to provide evidence for application of lipid lowering agents in treatment of diabetic retinopathy（DR）.METHODS：We searched the databases of Pub Med,Embase and Cochrane Library Central Register of Controlled Trials（CENTRAL）and abstracts from main annual meetings up to January 1,2017.Google scholar and Clinical Trials.gov were also searched for unpublished relevant studies.We included randomized controlled trials（RCTs）that studied lipid-lowering agents in type 1 or type 2 diabetes in this Meta-analysis.The primary endpoint was the progression of DR,and the secondary endpoints included vision loss,development of diabetic macular edema（DME）and aggravation of hard exudates.The pooled odds ratios（OR）with corresponding 95%confidence intervals（95%CIs）were calculated.RESULTS：After systemic and manual literature search by two independent investigators,we included 8 RCTs from 7 published articles with 13 454 participants in this Meta-analysis.The results revealed that lipid-lowering drugs were associated with reduced risk in DR progression[OR=0.77（95%CI：0.62,0.96）,P=0.02].Lipid-lowering agents might have protective effect on DME compared to placebo,although the difference was not statistically significant[OR=0.60（95%CI：0.34,1.08）,P=0.09].However,no significant differences in the worsening of vision acuity[OR=0.96（95%CI：0.81,1.14）,P=0.64]and hard exudates[OR=0.50（95%CI：0.15,1.74）,P=0.28]were found between the lipidlowering drugs and the placebo groups.CONCLUSION：In DR patients,lipid-lowering agents show a protective effect on DR progression and might be associated with reduced risk in the development of DME.However,lipid-lowering agents have no effects on vision loss and hard exudates aggravation.Further clinical trials in larger scale are required to confirm the conclusion of this study and thus justify the use of intensive control lipids with anti-lipid agents at the early stages of DR.

Lipid Oxidation in Mechanically Deboned Chicken Meat:Effect of the Addition of Different Agents

The study evaluated the effect of sodium chloride (1.5%), sodium erythorbate (0.5% and 1.0%) and ascorbic acid (0.1% and 0.2%) on inhibiting lipid oxidation in mechanically deboned chicken meat (MDCM). The peroxide, acidity, pH, color and odor values of the samples were determined on the 1st, 3rd and 5th days. Treatments with sodium erythorbate and ascorbic acid had significant influence (p ≤ 0.05) on the peroxide, acidity and pH values. Ascorbic acid and erythorbate sodium were especially effective in reducing lipid oxidation in mechanically deboned chicken meat.

A role for lipids as agents to alleviate stroke damage： the neuroprotective effect of 2-hydroxy arachidonic acid

Cerebrovascular accident（CVA）or stroke is one of the world＇s leading causes of death and permanent disability.The high social and medical costs associated with this pathology mean there is an urgent need to find effective therapies.Occlusion of the middle cerebral artery（MCAO）,mainly by clots,is the origin of most CVAs in humans.

Pyridocarbazole alkaloids from Ochrosia borbonica: lipid-lowering agents inhibit the cell proliferation and adipogenesis of 3T3-L1 adipocyte via intercalating into supercoiled DNA

Bioassay-guided fractionation of an ethanolic extract of Ochrosia borbonica led to the isolation of two known pyridocarbazole alkaloids,ellipticine(1)and 9-methoxyellipticine(2),and six known monoterpenoid indole alkaloids(3-8).Lipid-lowering assay in 3 T3-L1 cell model revealed that 1 and 2 could significantly inhibit the lipid droplet formation(EC50(28)0.41 and 0.92μmol·L^–1,respectively)and lower triglyceride levels by 50%-60%at the concentration of 1μmol·L^–1,being more potent than the positive drug luteolin(EC50(28)2.63μmol·L–^1).A mechanistic study indicated that 1 and 2 could intercalate into supercoiled DNA,which consequently inhibited the mitotic clonal expansion of 3 T3-L1 cells at the early differentiation phase,leading to the retardance of following adipogenesis and lipogenesis.These findings suggest that 1 and 2 may serve as promising leads for further d evelopment of anti-obesity drugs.

复合微生态制剂对宠物犬、猫血糖血脂的影响

该文选用3周岁美短猫、2周岁迷你杜宾犬及3.5周岁拉布拉多犬,以饲喂全价全期宠物粮为对照组,试验组为分别在全价全期宠物粮中添加2、3.5 g/d复合微生态制剂,以探究复合微生态制剂对宠物体重、血糖、血脂的影响。结果显示,复合微生态制剂对宠物体重调理具有较好效果,能够有效控制宠物体重,降低宠物血糖水平,对宠物血脂水平有较好的正向调节作用。

特发性膜性肾病患者脂代谢对免疫抑制剂联合糖皮质激素治疗效果的影响

目的探讨特发性膜性肾病患者脂代谢对免疫抑制剂联合糖皮质激素治疗效果的影响。方法86例行免疫抑制剂联合糖皮质激素治疗的特发性膜性肾病患者根据治疗效果分为未好转组和好转组,比较两组的基线资料和脂代谢指标,分析治疗效果的相关影响因素。结果治疗6个月后,86例特发性膜性肾病患者中16例未好转,占比18.60%。未好转组的TC、TG水平高于好转组(P<0.05)。Logistic回归分析显示,TC、TG水平是特发性膜性肾病患者免疫抑制剂联合糖皮质激素治疗效果的影响因素(OR>1,P<0.05)。结论特发性膜性肾病患者的脂代谢水平会对免疫抑制剂联合糖皮质激素的治疗效果产生影响。

THE EFFECTS OF RADIX SALVIAE MILTIORRHIZAE ON LIPID ACCUMULATION OF PEROXIDIZED LOW DENSITY LIPOPROTEIN IN MOUSE PERITONEAL MACROPHAGES ?LIPID ANALYSIS AND MORPHOLOGICAL STUDIES

Mouse peritoneal macrophages were incubated in DMEM with pox-LDL and Rradlx Salviae Miltiorrhizae (RSM) to investigate the effects of RSM on the internalization of peroxidized low density lipoprotein (pox-LDL) by using lipid analysis and electron microscopy. Lipid peroxide (LPO) concentrations were increased slightly in the medium after incubation of macrophages with normal LDL (n-LDL), while decreased significantly in the media after incubation of macrophages with pox-LDL. In the three groups with pox-LDL, it could be found that there was a dose-dependent decrease of concentrations of LPO and total cholesterol (TCH) in the two RSM groups, and the decrease in the two RSM groups was much greater than in the group without RSM. RSM accelerated a more decrease of LPO than cholesterol contents in the media containing pox-LDL. The ultrastructural studies also showed that RSM induced the accumulation of lipid droplets in the cytoplasm of mouse peritoneal macrophages. The results suggested that RSM could accelerate the phagocytosis and degradation of pox-LDL by macrophages.

血脂异常及脂代谢紊乱的中西医诊疗现状与前景

随着生活水平的不断提高,我国血脂异常及脂代谢紊乱的患者越来越多。西医研究开发了多种调节血脂的药物,还可以将不同类别的调脂药物联合应用,但是在临床实践当中仍发现许多不足之处。中医在临床实践中常用单味中药、中药复方、针灸、艾灸、推拿等方法调节血脂,具有安全有效、无不良反应的特点,发现中医结合西医用药可以明显提高对血脂异常及脂代谢紊乱患者的疗效,可以减轻药物带来的不良反应,具有良好的研究前景。

硒锌制剂拮抗慢性氟中毒的实验研究

目的 探讨硒锌制剂对慢性氟中毒的影响及其机理。方法 Wistar大鼠在饮含 5 0 mg/L高氟水的同时通过灌胃方式给予不同剂量的硒锌制剂 ,2个月后 ,测量大鼠尿液氟浓度和 r- GT活性 ,血液 GSH- Px活性及肾组织中 L PO水平、GSH含量和 SOD活性。结果 发现硒锌制剂通过促进尿氟排泄 ,增强全血 GSH - Px和肾SOD活性 ,增加肾 GSH含量而抑制氟中毒引起的脂质过氧化作用 ,从而降低尿 r- GT活性和肾 L PO含量。结论 提示一定剂量的硒锌制剂对慢性氟中毒有明显的拮抗作用 。

五种螯合剂对镉致小鼠脏器脂质过氧化作用的影响

[目的 ]开发高效低毒的新型解毒剂。 [方法 ]研究镉染毒组小鼠和N 对羟甲苯甲基 D 葡糖二硫代氨基甲酸钠 (HBGD)、N 苯甲基 D 葡糖二硫代氨基甲酸钠 (BGD)、二乙基二硫代氨基甲酸钠 (DDTC)、二巯基丙醇 (BAL)、乙二胺四乙酸 (EDTA)等五种螯合剂治疗组小鼠各脏器的脂质过氧化物 (LPO)值及血清乳酸脱氢酶 (LDH)、天冬氨酸转氨酶(AST)和丙氨酸转氨酶 (ALT)活性的变化。 [结果 ]氯化镉染毒 ( 2 5mgCd/kg ,腹腔注射 )后小鼠多数脏器LPO值和血清LDH、AST及ALT活性显著高于对照组。染镉 3 0min后用各螯合剂治疗 ( 4 0 0 μmol/kg ,腹腔注射 ) ,2 4h后除EDTA外 ,其余螯合剂均对镉引起的各脏器LPO值及血清LDH、AST、ALT活性的升高有显著的抑制作用 (P <0 0 5 ) ;染镉 2 4h后 ,注射各螯合剂 ,治疗 2 4h后 ,HBGD、BGD和DDTC显著抑制了上述各指标的升高 (P <0 0 5 )。 [结论 ]HBGD和BGD对镉致小鼠各脏器LPO值和血清LDH、AST及ALT活性升高的抑制效果最好 。

硒锌制剂拮抗氟毒性作用的实验研究

为研究硒锌制剂对氟毒性的影响 ,大鼠在饮高氟水的同时给予硒锌制剂 ,结果发现硒锌制剂可通过促进尿氟排泄 ,增加 GSH- Px和 SOD活性及 GSH含量而抑制氟引起的脂质过氧化 ,从而降低尿 γ- GT活性和 L PO水平。提示硒锌制剂对氟毒性具有明显的拮抗作用 ,其机理与促进尿氟排泄和抗脂质过氧化作用有关。

抗精神病药物治疗急性期体脂分布特征及其与血脂代谢相关性研究

目的 探讨抗精神病药物治疗急性期体脂分布特征及其与血脂代谢的关系。方法 对 4 6例入选患者采用自身配对设计 ,给予单一抗精神病药物 (APS)治疗 10周 ,检测患者治疗前后体重、体重指数 (BMI)和血脂 ,并采用结构核磁共振测定其中 4 0例患者治疗前后体脂指标 ,包括腹部皮下脂肪 (SUB)和内脏脂肪 (IAF)。结果 APS治疗前后患者体重指标差异有显著性 (P <0 0 5～P <0 0 0 0 1) ,体脂指标差异有显著性 (PSUB<0 0 5、PIAF<0 0 0 1) ,男性体脂指标变化值明显高于女性 ;血脂指标治疗前后差异有显著性 (P <0 0 1～P <0 0 0 0 1) ;治疗后体重指数(BMI)与甘油三酯 (TG)呈正相关 (r=0 391;P =0 0 14 ) ;体脂指标中IAF与低密度脂蛋白 (LDL)呈正相关 (r =0 4 38;P =0 0 1)。结论 APS治疗急性期体脂分布具腹型肥胖特征 ,男性更明显 。

降血脂和降血糖类中药及保健食品中违禁添加17种化学药物的液相色谱-离子阱质谱定性检测

建立了液相色谱-离子阱质谱法检测降血脂和降血糖类中药及保健食品违禁添加的17种化学药物。采用C18柱,分别以0.5%甲酸-乙腈和20mmol/L醋酸铵溶液-乙腈梯度洗脱,采用正离子扫描模式,17种药物的检测限为0.05～1.96ng。通过与标准谱库中保留时间和多级质谱图的双重对比,定性鉴别样品中违禁添加的17种化学药物。在300批供试品中,分别检测到格列吡嗪、格列本脲、苯乙双胍和洛伐他汀。

载药脂质超声微泡造影剂的制备及应用研究

载药脂质微泡是近年来国内外研究的热点之一,目前已制备出微米级及纳米级载药脂质微泡,本文就载药脂质超声微泡造影剂的特点、制备、应用、现存的问题及发展前景做一综述。

黄芪注射液对肾病综合征血脂及载脂蛋白的影响

目的探讨黄芪对肾病综合征(NS)患者血脂及载脂蛋白的影响。方法 54例NS患者随机分为治疗组与对照组,各27例。对照组给予常规治疗;治疗组在常规治疗(激素+对症处理)基础上,加用黄芪注射液(40 mL/d)静脉点滴。两组患者均于治疗前及治疗后4周取晨空腹静脉血2 mL,监测血脂及载脂蛋白变化。结果两组治疗后血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、极低密度脂蛋白胆固醇(VLD-C)、载脂蛋白B(apoB)均明显降低,高密度脂蛋白胆固醇(HLD-C)、载脂蛋白A1(apoA1)明显升高(P<0.01)。治疗后两组比较,差异有统计学意义(P<0.05)。结论黄芪具有调节肾病综合征患者血脂及载脂蛋白的作用,可以降低TC、TG、LDL-C、VLD-C及apoB,升高HLD-C及apoA1,具有降脂作用。

活性氧非酶促清除剂对老化种子的影响

种子老化是影响种子贮藏的关键问题。活性氧(reactive oxygen species,ROS)非酶促清除剂能延缓种子的老化,但其含量会因种子老化而下降。因此,合理添加ROS非酶促清除剂协助其内部酶系统共同清除种子内ROS,抑制种子的老化,从而延长种子的贮藏寿命,这将成为种质资源迁地保存研究的一个必然发展趋势。本文重点综述了ROS非酶促清除剂的种类及其对种子老化过程的影响,并系统分析了ROS非酶促清除剂在种子老化过程中的研究现状、存在问题及其研究前景,以期为研究种子老化过程中ROS非酶促清除剂的作用机理提供理论基础。

新型血脂调节药——依折麦布

依折麦布是一种具有新型作用机制的调血脂药,能选择性抑制肠道对食物中固醇(胆固醇和植物固醇)以及胆汁中胆固醇的吸收。该药通过肝肠循环可较长时间维持其药理作用,特殊的代谢途径使得它与许多药物间有临床意义的相互作用较少。可空腹或与食物同服,一般无需调整剂量。本品单用或与其他调血脂药联用为常见及难治的血脂异常疾病提供了新的补充疗法,且普遍耐受良好。

吉西他滨脂质衍生物聚合物胶束的制备及其理化性质和抗肿瘤活性

目的制备吉西他滨(Gem)脂质衍生物及其聚合物胶束,克服Gem体内易失活、不能口服和无靶向性的缺陷。方法合成N-苯甲酰-3'-乙酰吉西他滨(BAG)。用注入法制备载BAG的泊洛沙姆188胶束(BAG∶泊洛沙姆188=10∶1,mol/mol);用激光粒度和电位仪测定胶束的粒度和Zeta电位;胶束用负染法透射电镜法观察胶束微观形态。Gem或BAG聚合物胶束5,10,20,30,50,70和90μmol·L-1与人乳腺癌细胞MCF-7培养24,48和72 h,用MTT法测定对MCF-7细胞生长的抑制率。肝癌细胞H22移植瘤小鼠分别iv或ig给予Gem 40 mg·kg-1或BAG聚合物胶束62 mg·kg-1,间隔2 d给药1次,共3次,末次给药后第2天处死小鼠,测定抑瘤率。结果经薄层色谱法、核磁共振氢谱和碳谱、红外光谱和质谱验证,BAG的结构正确。BAG聚合物胶束外观为淡蓝色乳光的透明溶液,粒径为62.82 nm,Zeta电位为-18.8 mV,电镜下呈现球状均匀分布。MTT法实验结果表明,Gem和BAG聚合物胶束分别与MCF-7细胞培养24,48和72 h,其抑制MCF-7细胞生长的IC50分别为40.6和90.0,5.0和14.9,5.0和13.6μmol·L-1。体内实验结果表明,Gem口服和注射组与模型对照组比较(P<0.01)、BAG聚合物胶束口服和注射组与泊洛尔姆188空白胶束组比较(P<0.05,P<0.01)均具有明显的抑瘤作用;作用强度,BAG聚合物胶束口服优于Gem口服(P<0.05),BAG聚合物胶束注射优于其口服(P<0.05),BAG聚合物胶束注射与Gem注射作用相当。结论 Gem脂质衍生物能载入泊洛沙姆188聚合物胶束内。BAG聚合物胶束体外对MCF-7细胞生长有抑制作用,iv和ig给药对小鼠H22移植瘤均具有抑瘤作用。BAG聚合物胶束口服优于Gem口服,提示BAG聚合物胶束有望开发成为新型的抗肿瘤口服制剂。