The Hypolipidemic Effects of l-Acetyl-4-phenyl-l,2,4-triazolidine-3,5-dione in Rodents

l-Acetyl-4-phenyl-l ,2,4-triazolidine,5-dione (APTD), a potent hypolipidemic agent, lowered both serum cholesterol and triglyceride levels in normo- and hyperlipidemic rats at 10 or 20 mg/kg/day. The agent effectively lowered VLDL-cholesterol (VLDL-C) and LDL-C content and raised HDL-C content in normal and hyperlipidemic rats treated from 4 to 8 weeks. Similar effects on the incorporation of cholesterol into the lipoprotein fractions were observed after drug treatment. Tissue lipids, e.g. cholesterol, were lowered, whereas fecal cholesterol levels were increased. APTD's primary targets were acyl CoA cholesterol acyl transferase (ACAT) for cholesterol ester synthesis and sn-glycerol-3-phosphate acyl transferase (GPAT) and phosphatidylate phosphohydrolase (PPH) for triglyceride synthesis.     

锌对高脂血清培养乳鼠心肌细胞的作用

本实验研究了高脂血清和锌对培养的乳鼠心肌细胞作用。结果表明：高脂血清培养的心肌细胞搏动部位数明显减少，细胞出现明显的超微结构改变。同时心肌细胞脂质过氧化物（ＬＰＯ）明显增多，加锌则能明显增加细胞自发博动部位数，减少细胞内ＬＰＯ，并使细胞损伤明显减轻，结果提示高脂血清对培养的心肌细胞损伤与心肌细胞脂质过氧化有关，锌对高脂血清所致的心肌细胞损作胃保护作用。     

灵芝三萜抑制氧化应激对大鼠高脂性脂肪肝的防治作用

目的：探讨灵芝三萜抑制氧化应激防治大鼠高脂性脂肪肝的作用。方法：SD大鼠随机分为正常对照组,模型组,灵芝三萜低、中、高剂量组（GT-L、GT-M、GT-H组）和辛伐他汀组。用高脂饲料喂养建立大鼠高脂性脂肪肝模型。经12周给药后,分别测定各组血清总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白（HDL）、低密度脂蛋白（LDL）及肝组织中MDA,SOD,GSH-Px和T-AOC的含量;免疫印迹观察NOX2蛋白表达情况;光镜观察肝组织脂肪病变程度。结果：与模型组比较GT-M组、GTs-H组血清TC、TG、LDL含量均显著降低（P〈0．05或P〈0．011,GT-H组HDL含量显著增加（P〈0．05）;GT-M组、GT-H组肝匀浆中MDA含量较模型组相比均明显降低LP〈0．05或P〈0．01）,SOD,GSH-Px和总抗氧化能力水平较模型组相比均明显上升（P〈O．05或P〈0．01）。GT-H组可明显下调NOX2蛋白表达（P〈0．05）。GT-M组、GT-H组肝细胞脂肪变性程度明显减轻。结论：灵芝三萜能降低高脂性脂肪肝大鼠血脂水平,其对大鼠高脂性脂肪肝的防治作用可能与抑制氧化应激有关。     

Beneficial effects of cordycepin on metabolic profiles of liver and plasma from hyperlipidemic hamsters

In this study, ¹H NMR-based metabonomics was applied to evaluate the beneficial effects of cordycepin (3′-deoxyadenosine), a natural monomer compound, on endogenous metabolic profiles of liver and plasma from hyperlipidemic Syrian golden hamsters. Hyperlipidemia was successfully established in hamsters fed by a high-fat diet for 2 weeks. The hyperlipidemic hamsters were treated with an oral administration of simvastatin (2 mg kg^? 1) or cordycepin (140 mg kg^? 1) for consecutive 4 weeks. The metabolic profiles of plasma and intact liver tissues were established using ¹H NMR spectroscopy. The results showed higher contents of lipids (triglyceride and cholesterol), lactate, acetate, alanine, glutamine together with lower contents of choline-containing compounds (e.g. phosphocholine, phosphatidylcholine, and glycerophosphocholine), glucose, and glycogen in plasma and liver samples from hyperlipidemic hamsters than those in controls. Cordycepin afforded a little lipid-regulating activity on plasma but more beneficial effects on liver, implicating that cordycepin might have a protective effect on liver under fatty liver condition.     

Pharmacokinetic alterations in poloxamer 407-induced hyperlipidemic rats

1. Plasma lipid profile abnormalities in hyperlipidemia can potentially alter the pharmacokinetics of a drug in a complex manner. To evaluate these pharmacokinetic alterations in hyperlipidemia and to determine the underlying mechanism(s), poloxamer 407-induced hyperlipidemic rats (HL rats), a well-established animal model of hyperlipidemia have been used.

2. In this review, we summarize findings on the pathophysiological and gene expression changes in drug-metabolizing enzymes and transporters in HL rats. We discuss pharmacokinetic changes in drugs metabolized primarily via hepatic cytochrome P450 (CYPs) in terms of alterations in hepatic intrinsic clearance (CL^′_int), free fraction in plasma (f_u) and hepatic blood flow rate (Q_H), depending on the hepatic excretion ratio, as well as drugs eliminated primarily by mechanisms other than hepatic CYPs.

3. For lipoprotein-bound drugs, increased binding to lipoproteins resulted in lower f_u values and volumes of distribution, with some exceptions. Generally, slower non-renal clearance (or total body clearance) of drugs that are substrates of hepatic CYP3A and CYP2C is well explained by the following factors: alterations in CL^′_int (due to down-regulation of hepatic CYPs), decreased f_u and/or possible decreased Q_H.

4. These consistent findings across studies in HL rats suggest more studies are needed at the clinical level for optimal pharmacotherapies for hyperlipidemia.     

活血清解汤对高脂血症性胰腺炎大鼠瘦素的调控作用

目的 探讨活血清解汤对高脂血症性胰腺炎(HLAP)大鼠瘦素的调控作用及其机理.方法 将60 只SD 雄性大鼠随机分为3 组:正常对照组(NC 组),高脂血症性胰腺炎组(HLAP 组),活血清解汤组(HXQJ 组).采用高脂饲料喂养3 周后经腹腔注射L-精氨酸500 mg/100 g 体重制作大鼠高脂血症性胰腺炎模型,经注胃管给予生理盐水或中药1 mL/100 g 体重,每12 h 一次.各组分别造模后24 h、36 h 处死半数大鼠,观察血清淀粉酶、瘦素、TNF-α、IL-1β、IL-10 水平的释放以及胰腺病理学、胰腺组织中瘦素和瘦素受体表达的变化.结果 造模后24 h HLAP 组和HXQJ 组血清淀粉酶、瘦素和IL-1β、TNF-α水平均较NC 组升高(P<0.01),胰腺组织损害也明显增强(P<0.01),胰腺组织瘦素表达明显增高(P<0.01).HXQJ 组淀粉酶、IL-1β、TNF-α水平均较HLAP 组低(P<0.01),而瘦素和IL-10 水平以及瘦素、瘦素受体表达高于HLAP 组(P<0.01).造模后36 h,HLAP 组和HXQJ组淀粉酶、瘦素水平均下降,胰腺瘦素、瘦素受体表达也减弱(P<0.01),但HXQJ 组淀粉酶水平已回落至NC 组水平,而瘦素水平仍高于HLAP 组,HLAP 组和HXQJ 组IL-1β、TNF-α及IL-10 水平继续上升,胰腺病理损害进一步加重,但HXQJ 组IL-1β、TNF-α水平较HLAP 组低,而胰腺组织瘦素表达和IL-10 高于HLAP 组,胰腺损害也较轻(P<0.01).结论 活血清解汤能够通过上调瘦素及瘦素受体表达,调节细胞因子网络平衡,阻断炎症介质的级联效应,从而阻止HLAP 的发生和发展.     

泰脂安胶囊治疗高脂血症性脂肪肝的实验研究

目的：观察调脂药泰脂安胶囊对高脂血症性脂肪肝的治疗作用。方法：采用高脂饮食喂饲大鼠8周,诱导高脂血症性脂肪肝模型,实验分为泰脂安高、中、低(1 000,500,250 mg·kg^-1)剂量组、易善复对照组、模型组和正常组,检测各组肝指数、肝功能、血脂、肝脂、肝组织超氧化物歧化酶(SOD)、丙二醛(MDA)含量及肝组织学改变。结果：高脂血症性脂肪肝模型组肝指数、血脂、肝功能、肝脂显著升高(P<0.001),肝组织SOD明显下降(P<0.05),肝组织学轻中度脂肪变；泰脂安高、中剂量组血脂、肝功能均显著下降(P<0.001),肝脂明显下降(P<0.001,P<0.05),肝组织SOD明显升高(P<0.05),肝组织学接近正常。结论：泰脂安胶囊可安全有效的用于高脂血症性脂肪肝的治疗。     

黄金血康预防兔高脂血症和动脉粥样硬化

目的研究黄金血康对兔高脂血症和动脉粥样硬化形成的调节和预防作用。方法将实验兔分成正常对照组、动脉粥样硬化模型组和黄金血康预防组,分别喂普通饲料、高脂饲料和高脂饲料加黄金血康。2周后,所有的实验动物分别用气囊损伤兔腹主动脉内皮细胞,分别于实验前和实验第4、8、12周进行兔静脉采血,测定血清总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白胆固醇（HDL-C）、载脂蛋白AI（apoAI）和载脂蛋白B（apoB）的水平。结果模型组与对照组相比,其血清TC、TG显著升高,差异有高度统计学意义（P〈0.01）;预防性给药组与模型组相比,兔血清TC、TG、apoB降低,差异有统计学意义（P〈0.05或〈0.01）;而HDL-C、apoAI升高,差异有统计学意义（P〈0.05或〈0.01）。结论黄金血康对高脂血症兔脂质具有明显的调节作用,提示此药具有抗动脉粥样硬化形成的作用。     

大豆异黄酮对大鼠血脂和过氧化状态的影响

目的　观察大豆异黄酮 ( SI)对大鼠血脂水平及体内过氧化状态的影响。方法　 48只 Wistar大鼠随机分成四组 ,分别接受正常饲料、高脂饲料、高脂饲料添加 SI糖甙 30 0 mg/kg和高脂饲料添加 SI甙元 30 0 mg/kg处理。实验期 7周。结果　SI显著抑制高脂饲料所致的血浆甘油三酯水平升高 ,但对血浆总胆固醇 ,低密度脂蛋白胆固醇及高密度脂蛋白胆固醇变化几乎无影响。SI对进食高脂饲料引起的体内过氧化物水平升高具有显著拮抗作用 ,表现在降低肝脏及心肌中的自由基水平 ,升高肝脏超氧化物歧化酶和肝脏及心肌中谷胱甘肽过氧化物酶活性 ,减少血清及肝脏、心肌和主动脉中的脂质过氧化物含量。SI糖甙与其甙元的作用特征一致 ,仅在作用程度上略有差异。结论　 SI对高血甘油三酯有降低作用 ,并能改善高脂所致体内过氧化状态异常 ,减轻对机体的过氧化损伤。在大鼠饲料中 SI甙元的效果略优于 SI糖甙     

高脂血症性急性胰腺炎和胆源性急性胰腺炎临床特征分析

目的对比分析高脂血症性急性胰腺炎 （ hyperlipidemic acute pancreatitis, HLAP）和胆源性急性胰腺炎（ acute biliary pancreatitis, ABP）的临床特征。方法回顾性分析我院27例HLAP和61例ABP患者的临床表现、实验室指标、并发症、预后等。结果HLAP多见于中年男性患者,体重指数（ body mass index, BMI）偏高,常伴有脂肪肝、糖尿病。HLAP组ALT、AST、TBIL、DBIL、血Ca^2＋、血尿淀粉酶及手术率低于ABP组;HLAP组TG、TC、GLU及复发率高于ABP组（P〈0．05）。两组患者的临床严重程度分型、三种评分（Ranson评分、APACHE-Ⅱ评分、胰腺BalthazarCT评分）、白细胞计数、并发症、住院天数及病死率比较无差异（P〉0．05）。结论与ABP比较,HLAP患者具有自身的特征,容易漏诊及复发,治疗关键是降低血TG浓度。