益气活血解毒汤对实验性动脉粥样硬化家兔C反应蛋白及血脂水平的影响

目的利用高脂喂饲诱发动脉粥样硬化模型，探讨中药复方益气活血解毒汤对兔动脉粥样硬化的干预作用及其机制。方法24只日本雄性大耳白兔随机分为4组，每组6只，正常对照组、模型对照组、益气活血解毒汤组、辛伐他汀组。其中益气活血解毒汤组及辛伐他汀组边制模边给药，而前两组以等量蒸馏水灌胃。10周后，测定各组空腹血清三酰甘油（TG）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL—C）、高密度脂蛋白胆固醇（HDL—C）以及C反应蛋白（CRP）含量。结果模型对照组CRP、TG、TC及LDL—C较正常对照组有不同程度升高，HDL—C下降（P〈0.05或P〈0．01）。益气活血解毒汤组及辛伐他汀组CRP、TG、TC及LDL—C均明显低于模型对照组，HDL—C升高明显（P〈0.01），而与正常对照组比较无统计学意义（P〉0．05）。益气活血解毒汤组HDL—C与辛伐他汀组比较有所升高，差异有统计学意义（P〈0.05）。结论益气活血解毒汤对动脉粥样硬化有明显的预防和治疗作用。降低CRP和调节血脂可能是其作用机制之一。     

牛蒡根水提物对高脂血症大鼠血脂和动脉粥样硬化程度的影响

目的：观察牛蒡根水提物对高脂血症大鼠血脂及动脉粥样硬化程度的影响。方法将60只健康雄性Wista大鼠随机分为空白组、模型组、辛伐他汀组及牛蒡根水提物高、中、低剂量组,各10只。除空白组外均采用高脂饲料喂饲法建立高脂血症动物模型。辛伐他汀组给予辛伐他汀10 mg/kg每日灌胃,共7周。牛蒡根水提物高、中、低剂量组分别给予牛蒡根水提物8、4、2 g/kg每日灌胃,共7周。检测并比较各组大鼠实验前后血清甘油三酯（TG）、总胆固醇（TC）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、超氧化物歧化酶（SOD）、丙二醛（ MDA）水平,计算动脉粥样硬化指数（ AI）。光镜下观察各组大鼠实验前后主动脉弓形态学变化。结果牛蒡根水提物能够明显降低高脂血症大鼠的血清TC、LDL-C、TG和MDA水平,明显升高HDL-C和SOD水平,AI明显低于模型组（P均＜0．05）。牛蒡根水提物能够明显减少大鼠主动脉弓内膜下脂质沉积,降低动脉粥样硬化的病变程度。结论牛蒡根水提物能明显降低高脂血症大鼠TC、TG、LDL-C、MDA水平,升高HDL-C、SOD,具有明显降血脂及抗动脉粥样硬化的作用。     

依达拉奉对实验性高脂血症小鼠的影响

目的观察依达拉奉对高脂血症小鼠血脂的调节作用。方法18-22g雄性昆明小鼠随机分为空白对照组、高脂血症模型对照组、依达拉奉3mg／kg和6mg／kg组及辛伐他汀组。给药10d后眼眶取血，测定血清总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）含量，计算动脉粥样硬化指数（AI）及肝脏系数。结果与模型对照组比较，依达拉奉3mg／kg和6mg／kg组中血清HDL-C含量升高44．2％和81．4％（P均〈0．05）；AI降低33．8％和50．0％（P均〈0．05）；肝脏系数下降12.3％和13．8％（P均〈0．05）。结论依达拉奉具有调节血脂的作用。     

2型糖尿病血瘀证与血管内皮素、血栓素B2和6-酮-前列腺素的关系

目的 探讨2型糖尿病血瘀证与内皮素（ET）、血栓素B2（TXB2）和6-酮-前列腺素（6-keto-PGF1α）的关系。方法 采用放射免疫分析方法对2型糖尿病血瘀组和非血瘀组病人的血浆ET、TXB2和6-keto-PGF1α浓度进行测定。结果 同非血瘀证组相比，血瘀证组病人ET和TXB2明显增高（P〈0．05），6-keto-PGF1α水平则明显降低（P〈0.01），ET和TXB2同糖基化血红蛋白（HbAlc）水平呈正相关（r=0．506，P〈0．05；r=0．439,P〈0．05），6-ke-to-PGF1α水平同HbAlc水平呈负相关（r=-0．461，P〈0．05）。结论 ET、TXB2和6-keto-PGF1α水平可作为糖尿病血瘀证的微观辨证标志物。     

大黄蜇虫丸对血脂异常大鼠血栓素B2和6-酮-前列腺素1α的影响

目的研究大黄蜇虫丸对血脂异常大鼠血栓素(TX)B2和6-酮-前列腺素(6-Keto-PGF)1α影响,探讨大黄蜇虫丸对脂代谢紊乱的防治作用及机制。方法选用雄性Wistar大鼠,随机分为空白对照组、模型组、大黄蛰虫丸低剂量组、大黄蛰虫丸高剂量组、血脂康组。给予大鼠高脂饲料喂养复制脂代谢紊乱模型,空白对照组:给普通饲料,同时给予每日蒸馏水(10 ml/kg)灌胃;模型组:给高脂饲料,同时给予每日蒸馏水(10 ml/kg)灌胃;大黄蛰虫丸低剂量组:给高脂饲料,同时给予每日低剂量大黄蛰虫丸水提物灌胃(1 g/kg);大黄蛰虫丸高剂量组:给高脂饲料,同时每日给予高剂量大黄蛰虫丸水提物灌胃(2 g/kg);血脂康组:给高脂饲料,同时给予每日血脂康灌胃(0.2 g/kg);连续喂养8 w。末次给药后,禁食12 h,断头取血快速离心,留取血清、血浆标本,待用于各项指标检测。结果模型组与空白对照组相比,大鼠甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)均明显升高(P<0.05或P<0.01),而高密度脂蛋白胆固醇(HDL-C)明显降低(P<0.05);大黄蜇虫丸低、高剂量组与模型组相比,大鼠TG、TC、LDL-C均明显降低(P<0.05或P<0.01),而HDL-C明显升高(P<0.01)。模型组与空白对照组相比,大鼠TXB2明显升高(P<0.01),6-KetoPGF1α明显降低(P<0.01);大黄蜇虫丸低剂量组与模型组相比,大鼠TXB2明显降低(P<0.01),6-Keto-PGF1α明显升高(P<0.01);大黄蜇虫丸高剂量组与模型组相比,TXB2明显降低(P<0.01),6-Keto-PGF1α升高,但无统计学意义(P>0.05)。结论大黄蜇虫丸可以降低胆固醇、TG、LDL-C,升高HDL-C,调节血脂;低血浆中血栓素,升高6-Keto-PGF1α水平,调节血栓素/前列腺素平衡,抑制血小板活化,从而改善脂代谢紊乱。     

阿托伐他汀治疗高脂血症的疗效和安全性

目的　评价阿托伐他汀（北京红惠生物制药股份有限公司生产,商品名阿乐）治疗高脂血症,特别是高胆固醇血症和混合型高脂血症的疗效和安全性。方法　211例高脂血症患者随机分为两组A组阿托伐他汀组110例（高胆固醇血症和混合型高脂血症分别为58例和52例）,给予阿托伐他汀10mg/d;B组辛伐他汀组101例（高胆固醇血症和混合型高脂血症分别为48例和53例）,给予辛伐他汀10mg/d。4周后如未达有效标准,均可加量至20mg/d,治疗8周,观察降脂疗效和不良反应。结果　高胆固醇血症用阿托伐他汀治疗,总胆固醇(TC)从(6.59±0.66)mmol/L降至(4.62±1.45)mmol/L（下降29.9%）;低密度脂蛋白胆固醇(LDL-C)从(4.02±0.77)mmol/L降至(2.44±0.64)mmol/L（下降39.3%）;（TC－HDL-C）/HDL-C从3.93±1.22降至2.37±1.54（下降39.7%）（P均＜0.01）。阿托伐他汀降低LDL-C;（TC－HDL-C）/HDL-C作用优于同剂量的辛伐他汀（P均＜0.05）。对于混合型高脂血症患者,阿托伐他汀可使甘油三酯(TG)从(3.17±0.97)mmol/L降低至(2.21±1.03)mmol/L（P＜0.05）,作用亦明显优于辛伐他汀（P＜0.05）。结论　(1)阿托伐他汀有明显的降低TC、LDL-C、TG和（TC－HDL-C）/HDL-C作用,降低LDL-C、TG和（TC-HDL-C）/HDL-C作用明显优于同剂量的辛伐他汀,升高HDL-C作用则两组相似;(2)阿托伐他汀不良反应较轻微;(3)阿托伐他汀可用于高胆固醇血症和混合型高脂血症的治疗;(4)推荐常规剂量10mg/d,少数TC、LDL-C较高者可用20mg/d治疗。     

137例不同类型蛋白尿患者血脂水平测定及分析

选择。肾小球性蛋白尿患者75例（观察组1组）、肾小管性蛋白尿患者24例（观察2组）、混合性蛋白尿患者38例（观察3组）及健康查体者120例（对照组），检测空腹血清胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）水平。结果与对照组比较，观察1组血清TC、LDL-C、TG显著增高（P〈0．01、0．05），观察3组血清TC、LDL-C显著增高（P〈0．05）；与观察2组比较，观察1组和观察2组血清TC、LDL-C、TG均显著升高（P〈0．01、0．05）。认为肾小球性蛋白尿及混合性蛋白尿患者存在明显高脂血症，及时纠正脂质代谢紊乱对于改善肾脏病理改变，防止和延缓肾损伤具有重要意义。     

化瘀祛痰方通过调控HIF-1α/VEGF/VEGFR-2通路影响动脉粥样硬化家兔主动脉脂质斑块

目的研究化瘀祛痰方调控HIF-1α/VEGF/VEGFR-2通路对动脉粥样硬化家兔主动脉脂质斑块的影响,探讨化瘀祛痰方对动脉粥样硬化脂质斑块的作用机制。方法将60只新西兰家兔随机分为对照组15只,实验组45只。实验组45只家兔通过免疫性内皮损伤合并高脂饲料喂养的方法制备动脉粥样硬化模型,对照组喂饲普通饲料。8周后,将实验组家兔随机分为模型组、化瘀祛痰方组及辛伐他汀组。各组给予相应药物干预,对照组、模型组给予同体积生理盐水,每天1次,连续4周后取材。全自动生化分析仪检测各组血清甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDLC)、高密度脂蛋白胆固醇(HDLC)含量;HE和油红O染色观察家兔主动脉病理形态学改变,测量内膜、中膜厚度;免疫组化法测定CD31平均光密度值;ELISA检测血清缺氧诱导因子1α(HIF-1α)和血管内皮生长因子(VEGF)含量;Western blot法检测主动脉HIF-1α、VEGF、VEGFR-2蛋白表达。结果模型组血清TG、TC、LDLC水平较对照显著升高(P0.01),HDLC水平显著降低(P0.01),而化瘀祛痰方组和辛伐他汀组血清TG、TC、LDLC含量较模型组降低(P0.05或P0.01),HDLC含量均升高(P0.05或P0.01)。病理染色可见模型组主动脉内膜细胞增生,有大量泡沫细胞和脂质沉积,经化瘀祛痰方和辛伐他汀治疗后均可见明显改善。模型组内膜、中膜厚度较对照组显著增厚(P0.01),而化瘀祛痰方组和辛伐他汀组较模型组显著减小(P0.01)。模型组主动脉CD31平均光密度值较对照组显著升高(P0.01),而化瘀祛痰方组和辛伐他汀组较模型组显著降低(P0.01)。模型组血清HIF-1α和VEGF含量较对照组显著升高(P0.01),而化瘀祛痰方组和辛伐他汀组较模型组均降低(P0.05或P0.01)。模型组主动脉HIF-1α、VEGF、VEGFR-2蛋白表达较对照组显著升高(P0.01),经化瘀祛痰方和辛伐他汀治疗后,两组主动脉HIF-1α、VEGF、VEGFR-2蛋白表达水平较模型组均有显著降低(P0.01)。结论化瘀祛痰方稳定动脉粥样硬化脂质斑块,其机制可能与调控HIF-1α/VEGF/VEGFR-2通路抑制血管新生有关。     

辛伐他汀对冠心病患者血管内皮细胞功能障碍的治疗作用（英文）

目的：研究辛伐他汀对冠心病患者血管内皮细胞功能障碍的干预作用。方法：90例冠心病患者按LDL-C水平分为三组：辛伐他汀20mg组（37例,LDL-C≥2.5mmol/L）,辛伐他汀10mg组（35例,2.5mmol/L〉LDL-C≥1.8mmol/L）,常规治疗组（18例,LDL-C〈1.8mmol/L,未服辛伐他汀）,疗程均为8周。应用彩色多普勒超声诊断仪测量受试者肱动脉血流介导的舒张功能（FMD）。应用硝酸还原酶法检测受试者一氧化氮（NO）的含量。常规检测血清TC、TG、LDL-C及HDL-C的浓度。结果：8周后,与治疗前比较,辛伐他汀20mg,10mg组TC、TG和LDL-C浓度明显下降（P均〈0.05）,而HDL-C明显升高（P均〈0.05）;辛伐他汀20mg组与10mg组间各指标差异无显著性（P〉0.05）;与常规治疗组比较,辛伐他汀20mg、10 mg组FMD[（6.01±0.49）%比（9.01±0.39）%比（9.01±0.47）%]明显改善（P均〈0.01）、血清NO含量[（38.97±8.89）μmol/L比（47.67±10.89）μmol/L比（45.61±9.09）μmol/L]明显升高（P均〈0.05）,辛伐他汀20mg、10 mg组两组间NO和FMD亦无显著差异（P〉0.05）。结论：辛伐他汀可增加冠心病患者一氧化氮含量,改善血管内皮细胞功能,其作用机制与降低血清总胆固醇、甘油三酯和低密度脂蛋白可能有一定关系,但该作用无明显的量效关系,可能独立于降脂作用之外。     

阿托伐他汀治疗原发性高脂血症的疗效评价

目的评价阿托伐他汀治疗原发性高脂血症的疗效。方法 60例原发性高脂血症患者随机分为两组,在常规低脂饮食的基础上,治疗组服用阿托伐他汀10 mg,对照组服用辛伐他汀10 mg,均每晚1次,疗程8周。评价两组治疗前后血清总胆固醇（TC）、三酰甘油（TG）、低密度脂蛋白胆固醇（LDL-C）和高密度脂蛋白胆固醇（HDL-C）水平的变化。结果服药8周末与治疗前相比,两组TC、TG、LDL-C均显著下降（P〈0.05）,HDL-C均明显上升（P〈0.05）,但以治疗组更为显著。结论阿托伐他汀治疗原发性高脂血症疗效好。     

Classification and characterization of hereditary types 2A, 2B, 2C, 2D, 2E, 2M, 2N, and 2U (unclassifiable) von Willebrand disease.

All variants of type 2 von Willebrand disease (VWD) patients, except 2N, show a defective von Willebrand factor (VWF) protein (on cross immunoelectrophoresis or multimeric analysis), decreased ratios for VWF:RCo/Ag and VWF:CB/Ag and prolonged bleeding time. The bleeding time is normal and FVIII:C levels are clearly lower than VWF:Ag in type 2N VWD. High resolution multimeric analysis of VWF in plasma demonstrates that proteolysis of VWF is increased in type 2A and 2B VWD with increased triplet structure of each visuable band (not present in types 2M and 2U), and that proteolysis of VWF is minimal in type 2C, 2D, and 2E variants that show aberrant multimeric structure of individual oligomers. VWD 2B differs from 2A by normal VWF in platelets, and increased ristocetine-induced platelet aggregation (RIPA). RIPA, which very likely reflects the VWF content of platelets, is normal in mild, decreased in moderate, and absent in severe type 2A VWD. RIPA is decreased or absent in 2M, 2U, 2C, and 2D, variable in 2E, and normal in 2N. VWD 2M is usually mild and characterized by decreased VWF:RCo and RIPA, a normal or near normal VWF multimeric pattern in a low resolution agarose gel. VWD 2A-like or unclassifiable (2U) is distinct from 2A and 2B and typically featured by low VWF:RCo and RIPA with the relative lack of high large VWF multimers. VWD type 2C is recessive and shows a characteristic multimeric pattern with a lack of high molecular weight multimers, the presence of one single-banded multimers instead of triplets caused by homozygosity or double hereozygosity for a mutation in the multimerization part of VWF gene. Autosomal dominant type 2D is rare and characterized by the lack of high molecular weight multimers and the presence of a characteristic intervening subband between individual oligimers due to mutation in the dimerization part of the VWF gene. In VWD type 2E, the large VWF multimers are missing and the pattern of the individual multimers shows only one clearly identifiable band, and there is no intervening band and no marked increase in the smallest oligomer. 2E appears to be less well defined, is usually autosomal dominant, and accounts for about one third of patients with 2A in a large cohort of VWD patients.     

Different RBC aggregating properties of the Aalpha2Bbeta2gammaA2 and Aalpha2Bbeta2gammaAgamma' subpopulations of human fibrinogen

Human fibrinogen (TF) has been separated into two fractions: F1 - homodimers with respect to the gamma chain, and F2 - heterodimers composed of gammaA and gamma' polypeptides. Their rouleaux-inducing properties were as follows: (1) both, at the same concentration of 0.8%, were less effective than TF; (2) F1 produced larger rouleaux even under static conditions of a hemocytometer where F2 was silent; (3) F2 induced the process when a suspension was gently sheared between microscopic slides. Since the synthetic peptide gamma'(414-427) inhibited the rouleau formation in a mixture with F2, the C-terminal amino acids of the gamma' polypeptide probably bind the molecule to the cell. The inhibition was feebly visible in the native ratio of F1/F2, implicating a compensatory effect of F1.     

Structure-function of Hb Marseille-Long Island [alpha 2 beta 2 N-methionyl-2(NA2) His----Pro

Suspensions of red cells containing Hb Marseille-Long Island showed decreased oxygen affinity and low interaction with 2,3-diphosphoglycerate. Oxygen equilibrium studies of the purified component confirmed these abnormalities. Oxidation rate measurements of carbonmonoxy-Hb Marseille and carbonmonoxy-Hb A by ferricyanide showed an increased rate for the former, suggesting an increased dissociation constant for carbon monoxide. Nuclear Magnetic Resonance spectra in the high field region revealed small changes in the proximal region of the heme pocket. These results indicated that the mutation causes a perturbation at a distance from the mutation site.     

Identification of SH2B2beta as an inhibitor for SH2B1- and SH2B2alpha-promoted Janus kinase-2 activation and insulin signaling

The SH2B family has three members (SH2B1, SH2B2, and SH2B3) that contain conserved dimerization (DD), pleckstrin homology, and SH2 domains. The DD domain mediates the formation of homo- and heterodimers between members of the SH2B family. The SH2 domain of SH2B1 (previously named SH2-B) or SH2B2 (previously named APS) binds to phosphorylated tyrosines in a variety of tyrosine kinases, including Janus kinase-2 (JAK2) and the insulin receptor, thereby promoting the activation of JAK2 or the insulin receptor, respectively. JAK2 binds to various members of the cytokine receptor family, including receptors for GH and leptin, to mediate cytokine responses. In mice, SH2B1 regulates energy and glucose homeostasis by enhancing leptin and insulin sensitivity. In this work, we identify SH2B2beta as a new isoform of SH2B2 (designated as SH2B2alpha) derived from the SH2B2 gene by alternative mRNA splicing. SH2B2beta has a DD and pleckstrin homology domain but lacks a SH2 domain. SH2B2beta bound to both SH2B1 and SH2B2alpha, as demonstrated by both the interaction of glutathione S-transferase-SH2B2beta fusion protein with SH2B1 or SH2B2alpha in vitro and coimmunoprecipitation of SH2B2beta with SH2B1 or SH2B2alpha in intact cells. SH2B2beta markedly attenuated the ability of SH2B1 to promote JAK2 activation and subsequent tyrosine phosphorylation of insulin receptor substrate-1 by JAK2. SH2B2beta also significantly inhibited SH2B1- or SH2B2alpha-promoted insulin signaling, including insulin-stimulated tyrosine phosphorylation of insulin receptor substrate-1. These data suggest that SH2B2beta is an endogenous inhibitor of SH2B1 and/or SH2B2alpha, negatively regulating insulin signaling and/or JAK2-mediated cellular responses.