水芹黄酮对小鼠急性酒精性肝损伤的保护作用

建立小鼠急性酒精性肝损伤模型,分为空白组、模型组、阳性药对照组,水芹黄酮高、中、低剂量组。除空白组外,其余5组小鼠建立急性酒精性肝损伤模型后,空白组、模型组灌胃生理盐水;阳性药对照组灌胃还原性谷胱甘肽钠（0.5 g·kg-1·d-1）;水芹黄酮高、中、低3组（剂量分别为0.8、0.4、0.2 g·kg-1·d-1）;均连续灌胃10 d。记录小鼠体质量及肝指数,观察肝组织病理学变化,检测血清中相关指标变化。结果表明,水芹黄酮对急性酒精性肝损伤有保护作用,初步判断与抗脂质过氧化、调节脂类代谢、减少炎症因子释放有关。     

芍甘附子汤配方颗粒抗炎、镇痛作用研究

摘要：目的:观察芍甘附子汤配方颗粒的抗炎、镇痛作用。方法:采用二甲苯致小鼠耳廓肿胀实验、醋酸致小鼠腹腔毛细血管通透性增高实验观察芍甘附子汤配方颗粒的抗炎作用,50只昆明小鼠随机分为5组:模型组、地塞米松组(5 mg·kg-1·d-1)、芍甘附子汤配方颗粒高(6 g·kg-1·d-1,以生药计)、中(3 g·kg-1·d-1,以生药计)、低(1.5 g·kg-1·d-1,以生药计)剂量组,每组10只,各实验组连续灌胃给药3 d,2次/d,给药间隔不低于4 h,模型组给与等体积0.5%CMC-Na溶液;采用小鼠醋酸扭体实验、小鼠热刺激反应实验观察芍甘附子汤配方颗粒的镇痛作用,50只昆明小鼠随机分为5组:模型组、布洛芬组(250mg·kg-1·d-1)、芍甘附子汤配方颗粒高(6 g·kg-1·d-1,以生药计)、中(3 g·kg-1·d-1,以生药计)、低(1.5 g·kg-1·d-1,以生药计)剂量组,每组10只,给药方法同前。结果:与模型组相比,芍甘附子汤配方颗粒各剂量组可降低二甲苯所致小鼠耳廓肿胀度（P<0.01）,抑制醋酸诱导的小鼠腹腔毛细血管通透性增高（P<0.05或P<0.01）。芍甘附子汤配方颗粒各剂量组可减少醋酸所致小鼠疼痛的扭体次数（P<0.01）,高、中剂量组还可显著延长小鼠的扭体潜伏期（P<0.01）。芍甘附子汤配方颗粒高、中剂量组的热板痛阈值较模型组增加（P<0.05或P<0.01）。结论:芍甘附子汤配方颗粒具有一定的抗炎、镇痛作用。     

黄连素抗动脉粥样硬化的效果及作用机制研究

目的 研究黄连素对动脉粥样硬化小鼠抗动脉粥样硬化的效果及作用机制.方法 选取24只健康雄性SD小鼠,制作动脉粥样硬化模型,全部建模成功,随机分为模型组、辛伐他汀组、黄连素低剂量组、黄连素高剂量组,每组6只;正常组小鼠6只.正常组及模型组给予0.9％氯化钠溶液灌胃治疗,辛伐他汀组使用辛伐他汀10 mg·kg-1·d-1配...     

益气化浊胶囊对KKAy小鼠骨骼肌组织中葡萄糖转运蛋白4表达的影响

目的通过研究益气化浊胶囊对KKAy糖尿病小鼠骨骼肌组织中葡萄糖转运蛋白4(GLUT-4)蛋白表达的影响,探讨其改善胰岛素抵抗的作用机制。方法选用自发型2型糖尿病KKAy小鼠作为动物模型,喂以高脂饲料。以益气化浊胶囊高剂量(2g·kg-1·d-1)、低剂量(1g·kg-1·d-1)灌胃动物,设吡格列酮(2.5mg·kg-1·d-1)为阳性对照组,空白对照组选取与KKAy小鼠同源的C57BL/6J小鼠,喂以普通饲料。给药10周后处死小鼠,取骨骼肌组织,用蛋白印迹法检测GLUT-4蛋白表达水平。结果与空白对照组相比,模型组中骨骼肌GLUT-4蛋白表达水平显著降低;与模型对照组相比,益气化浊胶囊高、低剂量组、阳性对照组GLUT-4蛋白表达水平均有不同程度升高。结论益气化浊胶囊能够改善KKAy小鼠胰岛素抵抗情况,其作用机制之一可能与其上调骨骼肌中GLUT-4蛋白表达水平,加强外周组织对葡萄糖的转运有关。     

牛磺酸对东莨菪碱所致记忆获得性障碍模型小鼠的改善作用

目的观察牛磺酸对东莨菪碱所致模型小鼠学习记忆及对其脑组织M胆碱受体结合力的影响。方法将昆明小鼠随机分组,设立正常对照组,东莨菪碱模型组及阳性对照药(吡拉西坦)组,牛磺酸小剂量组(0.3g·kg-1),中剂量组(0.75g·kg-1),大剂量(1.875g·kg-1)组,分别灌胃给药,于d5,除正常对照组腹腔注射生理盐水外,其它各组注射东莨菪碱1mg·kg-1,20min后进行Morris水迷宫测试,测试5d后处死,取其脑组织进行M受体结合力测定。结果在行为学实验中,牛磺酸各剂量组游出时间与模型组相比有明显缩短(P<0.05),并可以提高模型小鼠M胆碱受体的结合力。结论牛磺酸对东莨菪碱所致模型小鼠学习记忆障碍及M受体有一定的改善作用。     

酵母致小鼠高尿酸血症模型

目的　建立小鼠高尿酸血症模型。方法　采用酵母膏灌胃给药 ,磷钨酸法测定不同时间小鼠血清尿酸水平。结果　 30、1 5g·kg- 1 ·d- 1 连续灌胃 1、2、3、4wk ,小鼠血清尿酸水平分别为 :(2 71 8± 53 2 )、(2 1 5 4± 31 5)、(1 95 9±56 0 )、(1 4 2 1± 30 7) μmol·L- 1 ,(2 2 6 8± 40 7)、(1 76 9±2 7 0 )、(1 4 8 67± 30 4)、(1 1 9 3± 2 7 4) μmol·L- 1 。 7 5g·kg- 1 ·d- 1 连续灌胃 1wk ,小鼠血清尿酸水平为 (1 1 7 0±2 9 0 ) μmol·L- 1 ,对照组小鼠血清尿酸为 (1 0 8 1± 1 3 9)μmol·L- 1 。结论　酵母膏灌胃可以复制出小鼠高尿酸血症模型 ,以 1 5～ 30 g·kg- 1 ·d- 1 连续灌胃 1～ 2wk较好     

气血并治方有效组分对载脂蛋白E基因敲除小鼠动脉粥样硬化不稳定斑块的干预作用

目的探讨气血并治方水提取物有效组分(CWQB)配伍对载脂蛋E基因敲除(ApoE-)小鼠晚期动脉粥样硬化不稳定斑块的干预作用及其可能的作用机制。方法6周龄ApoE-小鼠,给予高脂饲料,随机分为模型组、辛伐他汀2.5mg·kg-1组、CWQB 72和360mg·kg-1组。从24周龄起灌胃给药,每日1次,连续12周。同时取同龄C57BL/6小鼠作为正常对照。36周龄时麻醉处死,检测血脂水平和主动脉病理变化,免疫组织化学及计算机图像处理系统分析主动脉斑块中巨噬细胞内CD68的表达和平滑肌细胞内α-肌动蛋白的表达。结果CWQB及辛伐他汀均能降低小鼠的血脂水平,降低其胆固醇含量,升高高密度脂蛋白水平。CWQB大剂量组和辛伐他汀组可见主动脉斑块纤维帽厚度增加,斑块面积和管腔面积的比值下降;斑块中平滑肌细胞内α-肌动蛋白表达增加,巨噬细胞内CD68表达减少。结论CWQB具有一定的消减和稳定主动脉斑块的作用,其机制可能与其降低血脂水平、减少斑块内巨噬细胞浸润和增加血管平滑肌细胞数量有关。     

芙蓉李总多酚提取物对D-半乳糖所致亚急性衰老小鼠的影响

目的 观察芙蓉李总多酚提取物对D-半乳糖所致亚急性衰老小鼠的SOD、GSH-Px、MDA的影响。 方法 昆明种小鼠60只,雄性。随机分为空白对照组,衰老模型组,阳性对照组,芙蓉李低剂量组、中剂量组、高剂量组。阳性对照组以维生素E软胶囊100 mg.kg-1.d-1灌胃给药,芙蓉李总多酚低、中、高剂量组分别以100 mg.kg-1.d-1、200 mg.kg-1.d-1、300 mg.kg-1.d-1灌胃给药,空白对照组与衰老模型组灌胃同体积的生理盐水,每日一次,连续灌胃42 d。给药的同时,模型组与给药组小鼠,每日按注射剂量125 mg.kg-1.d-1 颈背部皮下注射D-半乳糖,空白对照组小鼠皮下注射生理盐水。 结果 芙蓉李总多酚提取物给药组可以显著增强血清SOD活力,降低MDA含量,显著增强肝、脑组织SOD、GSH-Px活力,降低MDA含量,与模型组比较,P ＜0.05。 结论 不同剂量的芙蓉李总多酚提取物均能拮抗自由基损伤,具有抗氧化延缓衰老的作用,可能的机理是通过增加体内抗氧化酶的活性、减少过氧化脂质的生成,从而提高机体抗氧化能力而导致的。     

仙牛颗粒的降血糖作用研究

［摘要］目的观察仙牛颗粒对大鼠实验性糖尿病血糖的影响。方法采用链脲佐菌素复制糖尿病模型大鼠60只，随机分为6组，每组10只，分别给予仙牛颗粒0.30，1.20 g·kg-1·d-1,二甲双胍150 mg·kg-1·d-1 （阳性对照组），灵菊七1.00，4.00 g·kg-1·d-1， 羧甲基纤维素钠（CMC Na，模型对照组）20 mg·kg-1·d-1 。另设一组空白对照组（给予等体积0.5% CMC Na）。0.5%连续给药14 d后，分别测定大鼠的血糖。结果仙牛颗粒可显著降低糖尿病大鼠的血糖，与模型对照组比较，差异有显著性（P＜0.05）。结论仙牛颗粒剂具有降低糖尿病大鼠血糖的作用。     

四君子汤配方颗粒与传统汤剂对实验性大鼠脾虚改善作用的比较研究

摘要：目的:比较四君子汤配方颗粒与传统汤剂对实验性大鼠脾虚改善作用的差异。方法:90只SD大鼠随机分为9组:正常对照组、模型组、传统汤剂低(以生药材计1.485 g·kg-1·d-1)、中(以生药材计2.97 g·kg-1·d-1)、高(以生药材计5.94 g·kg-1·d-1)剂量组、配方颗粒汤剂低(以生药材计1.485 g·kg-1·d-1)、中(以生药材计2.97 g·kg-1·d-1)、高(以生药材计5.94 g·kg-1·d-1)剂量组、阳性对照组(枸橼酸莫沙必利分散片,5 mg·kg-1·d-1),每组10只。采用小承气汤法、劳倦法及饥饿法三因素复合法复制脾气虚证模型后,灌胃给药,15 d后处死大鼠。采用ELISA法测定血清中血清生长激素释放肽（Ghrelin）、胃泌素（GAS）和胃动素（MLT）的含量,甲苯胺蓝染色法对大鼠胃窦肥大细胞（MC）及MC脱颗粒计数。结果:与正常对照组比较,模型组大鼠血清中Ghrelin、GAS和MLT的含量显著降低（P<0.05）,MC及MC脱颗粒数量显著升高（P<0.05）;与模型组比较,四君子汤配方颗粒与传统汤剂各组血清中Ghrelin、GAS和MLT的含量显著升高（P<0.05）,MC及MC脱颗粒数量显著降低（P<0.05）,配方颗粒与传统汤剂两者之间比较差异无统计学意义（P>0.05）。结论:四君子汤配方颗粒与传统汤剂均能改善对实验性大鼠脾虚症状,两者作用无显著差异。     

Synthetic nano-low density lipoprotein as targeted drug delivery vehicle for glioblastoma multiforme

The low density lipoprotein (LDL) receptor has been shown to be upregulated in GBM tumor cells and is therefore a potential molecular target for the delivery of therapeutic agents. A synthetic nano-LDL (nLDL) particle was developed and tested to determine its utility as a drug delivery vehicle targeted to GBM tumors. nLDL particles were constructed by combining a synthetic peptide containing a lipid binding motif and the LDL receptor (LDLR) binding domain of apolipoprotein B-100 with a lipid emulsion consisting of phosphatidyl choline, triolein, and cholesteryl oleate. Composition analysis, fast protein liquid chromatography, and electron microscopy revealed that nLDL was highly reproducible and intermediate in size between high density lipoprotein and LDL particles (10.5+/-2.8 nm diameter). The binding and uptake of fluorescently labeled nLDL particles was assessed using fluorescence microscopy. Uptake of nLDL was time dependent, exhibiting saturation at approximately 3 h, and concentration dependent, exhibiting saturation at concentrations greater than 5 microM peptide. Using Lysotracker as a cellular marker, nLDL co-localized with lysosomes. nLDL binding was eliminated by blocking LDLRs with suramin and nLDL inhibited binding of plasma LDL to LDLRs. Collectively these data strongly suggest that the synthetic nano-LDLs described here are taken up by LDLR and can serve as a drug delivery vehicle for targeting GBM tumors via the LDLR.     

血液透析冠心病患者低密度脂蛋白/高密度脂蛋白与氧化应激的临床研究

目的:探讨血液透析冠心病患者血脂低密度脂蛋白(LDL)/高密度脂蛋白(HDL)与氧化应激的临床意义。方法:采用回顾性方法分析2010年1月—2013年12月住院的所有血液透析合并冠心病患者临床资料。对照组为无冠心病者33例,观察组为冠心病者20例,分别检测各组患者LDL,HDL、血清晚期蛋白氧化产物(AOPPs)、血清超氧化物歧化酶(SOD)及丙二醛(MDA)等变化。结果:两组的HDL及LDL/HDL比较,差异有统计学意义(P<0.05),两组的SOD,MDA及AOPPs比较,差异有统计学意义(P<0.05)。提示冠心病患者中LDL明显升高,而HDL明显降低,同时存在明显的氧化应激产物水平升高。采用逐步回归相关分析研究,经过逐步拟合,得出回归方程:y=6.884-4.811X2+1.249X3-0.057X4,结果表明LDL/HDL比值与LDL,HDL及SOD存在线性回归关系。由标准回归系数看出LDL/HDL比值与LDL关系最大。结论:在血液透析冠心病患者中,其血脂LDL/HDL比值变化可能与氧化应激之间存在一定的相关性。     

Impact of short‐term low‐dose atorvastatin on low‐density lipoprotein and high‐density lipoprotein subfraction phenotype

Statins can significantly reduce low‐density lipoprotein–cholesterol (LDL‐C) and modestly raise or not alter high‐density lipoprotein–cholesterol (HDL‐C). However, their impact on high‐density lipoprotein (HDL) and low‐density lipoprotein (LDL) subfractions has been less examined. The aim of the present study was to investigate the short‐term impact of low‐dose atorvastatin on HDL and LDL subfractions in humans. In this randomized study, data from 52 subjects were analysed. Thirty‐seven patients with atherosclerosis were randomized to treatment with atorvastatin 10 mg/day (n = 17) or 20 mg/day (n = 20) for 8 weeks, with 15 healthy subjects without therapy used as a control group. The lipid profile and lipoprotein subfractions were determined using the Lipoprint system at baseline and at 8 weeks. The data suggest that atorvastatin treatment (10 and 20 mg/day) for 8 weeks significantly decreases LDL‐C levels and reduces the cholesterol concentration of all LDL subfractions, which is accompanied by an increase of the mean LDL particle size. Although 10 mg/day atorvastatin treatment for 8 weeks had no impact on the HDL subfraction, 20 mg/day atorvastatin for 8 weeks significantly increased the cholesterol concentration of large HDL particles and decreased the cholesterol concentration of small HDL particles without changing serum HDL‐C levels in patients with atherosclerosis. Therefore, the results suggest that 20 mg/day atorvastatin treatment for 8 weeks may result in a favourable modification of the HDL subfraction phenotype in addition to its effects on the cholesterol concentration of all LDL subfractions and mean LDL particle size.     

Effects of ethyl-CPIB (clofibrate) on tissue lipoprotein lipase and plasma post-heparin lipolytic activity in rats

The role of LPL in reducing the serum triacylglycerol concentration was investigated in rats fed a high sucrose diet containing 0.25% (w/w) ethyl-CPIB. Compared with sucrose-fed controls, drug treatment resulted in a fall in adipose tissue LPL activity and a rise in enzyme activity in thigh and heart muscle. Serum post-heparin lipoprotein lipase activity after a high dose of heparin was lower in ethyl-CPIB-treated rats than controls, but after a low dose of heparin the values were similar. The amount of LPL activator was decreased by the drug. Thus, the low serum triacylglycerol concentration observed in the ethyl-CPIB-treated rats cannot be explained by changes in functional LPL activity. The plasma triacylglycerol-lowering effect of the drug could be explained by the observed decrease in triacylglyerol output by the liver.     

Activation of membrane outward currents by human low density lipoprotein in mouse peritoneal macrophages

Summary The aim of the present study was to search for electrophysiological effects of human lipoproteins on membrane currents in mouse peritoneal macrophages which had been cultured for 5 to 20 days. Whole-cell currents were recorded by using a voltage-clamp technique.Low density lipoprotein (LDL, 100 g/ml) increased a slowly activating nonspecific cation current (i_so) in the positive potential range to 244 ± 23% of the reference (test potential + 55 mV, n = 13, P < 0.005). Augmentation of current resulted out of a negative shift of the activation curve along the voltage axis (–22 mV) and an increase of maximally available current.Furthermore, LDL increased a rapidly activating outward current (i_fo) at test potentials positive to the potassium equilibrium potential. At +55 mV i_fo-amplitude increasedto 165 ± 14% ofreference (n = 16, P < 0.005). LDL-induced effects on i_fo-current could be mimicked by application of the calcium ionophore A 23187 (1 mol/l) which led to an increase of i_fo-current to 161 ± 25% of the reference (test potential + 55 mV, n = 11, P < 0.005).Acetylated-LDL (100 g/ml, 5–15 min) produced no significant effect on the membrane currents under investigation. Correspondence to U. Borchard at the above address     

Phospholipid hydrolysis in serum lipoproteins by a basic phospholipase A2 from Naja nigricollis snake venom and an acidic phospholipase A2 from Naja naja atra snake venom

Apparent Km and Vmax values for PC and PE hydrolysis were determined following exposure of HDL, LDL, and VLDL to a basic phospholipase A2 from N. nigricollis snake venom and an acidic phospholipase A2 from N. nigricollis snake venom and an acidic phospholipase A2 from N. n. atra snake venom. Both enzymes hydrolyzed the lipoprotein phospholipids approximately as fast as they hydrolyzed pure phospholipids in mixed micelles, however, the N. nigricollis enzyme, which has a much stronger anticoagulant effect than the N. n. atra enzyme, had lower apparent Vmax values. These values were highest for phospholipids in VLDL and lowest for HDL, however, the differences between the lipoproteins were relatively small with the N. nigricollis enzyme while the differences were much larger with the N. n. atra enzyme. Fractions of the two enzymes in which varying numbers of lysines were carbamylated showed much larger differences in relative rates of phospholipid hydrolysis in HDL, LDL and VLDL. Triton X-100 eliminates these differences in rates of hydrolysis. These results are discussed in terms of the differences in the organized structure of the lipoprotein classes and in the penetration ability of the phospholipases.     

瑞香素对血清脂质及脂蛋白胆固醇含量的影响

瑞香素(daphnetin)系瑞香科植物长白瑞香(Daphne koreana Nakai)中的有效单体,化学结构为7,8-二羟基香豆素,并已由长春春城制药厂人工合成。药理实验证明有扩张冠状血管、增加冠脉流量,改善心肌代谢作用,并有抑制实验性“关节炎”及兴奋垂体—肾上     

人血高密度脂蛋白生物活性测定方法的研究

目的 :建立人血高密度脂蛋白 (HDL)生物活性检测法。方法 :根据受体酶联免疫检测法的原理和步骤 ,以超速离心制备的HDL为参考品 ,以每 1 μgapoAⅠ为一个HDL活性单位 ,通过HDL生物活性标准曲线双对数回归方程 ,求测待测HDL制剂的生物活性。结果 :标准曲线在 1～ 1 6个活性单位范围内呈线性关系。测定的板内及板间变异系数分别为 7.6 %～ 9.5 %及 1 2 .3%。结论 :此法操作简便 ,重复性好 ,且HDL以外的脂蛋白不干扰检测反应 ,可作为检测人血浆HDL制剂生物活性的方法。     

瑞香素对血清脂质及脂蛋白胆固醇含量的影响

Daphnetin is one of the components of Daphne koreana Nakai and the sample used in the experiment is the synthesized product. The compound was shown to possess obvious effect on lipid and lipoprotein cholesterol contents in the serum of normal and hyperlipidemic mice or rats. When daphnetin was given orally to rats, the serum level of high density lipoprotein cholesterol and the ratio of high density lipoprotein cholesterol to total cholesterol of normal rats were raised, whereas no significant effect on the level of lipid in normal mice was observed. Daphnetin (800 mg/kg, po for 1 week) decreased significantly the total cholesterol content in the serum of yolk(0.5 ml) treated mice. In addition, when daphnetin was given orally at a dosage of 800 mg/kg day for 2 weeks, the serum level of total cholesterol decreased. The sernm concentration of high density lipoprotein cholesterol and the ratio of high density lipoprotein cholesterol to total cholesterol in rats with hyperlipidemia increased significantly.     

精神障碍与脂代谢的相关性研究

目的探讨精神障碍与脂代谢之间有无相关性,以期能找到一些精神障碍的病因,从而为预防和治疗提供一些有益的帮助。方法精神障碍患者（观察组）的血脂资料与健康体检者（对照组）血脂资料进行对比。结果观察组甘油三酯（TG）降低与低密度脂蛋白（LDL）升高,与对照组比较,差异具有统计学意义（P〈0.05）。总胆固醇（T-CHO）与高密度脂蛋白（HDL）与对照组相比差异无统计学意义（P〉0.05）。结论甘油三酯降低和低密度脂蛋白升高与精神障碍之间有相关性,总胆固醇和高密度脂蛋白与精神障碍之间无相关性。