Correlation between Fc γ R III a and aortic atherosclerotic plaque destabilization in ApoE knockout mice and intervention effects of effective components of Chuanxiong Rhizome and Red Peony Root

Objective  

To explore the correlation between Fc γ RIII A (CD16A) and aortic atherosclerotic plaque destabilization in apoE knockout (apoE KO) mice and the intervention effects of effective components of Chuanxiong Rhizome and Red Peony Root.     

解毒活血配伍方药对载脂蛋白E基因敲除小鼠血清超敏C反应蛋白的影响

目的 观察解毒活血配伍方药对载脂蛋白E基因敲除［apolipoprotein E gene knock out,ApoE( / ) mice］小鼠血清超敏C反应蛋白（hs CRP）的影响。方法 13周龄110只ApoE( / )小鼠分为高脂饲料组（98只,给予高脂饲料）,普通饲料组（12只,给予普通饲料）,同时设13周龄C57 BL/6J小鼠作为正常对照组（12只,给予普通饲料）。19周后随机抽取高脂饲料ApoE( / )小鼠2只确认易损斑块形成后,剩余96只随机分为8组（模型组、解毒组、活血组、解毒活血配伍高、中、低剂量组、洛伐他汀组和血脂康组）,每组12只。造模成功后每天给予药物干预,解毒组予虎杖提取物266 mg/kg;活血组予芎芍胶囊110 mg/kg;配伍高剂量组予虎杖提取物53.2 mg/kg,芎芍胶囊220 mg/kg;配伍中剂量组给予虎杖提取物26.6 mg/kg,芎芍胶囊110 mg/kg;配伍低剂量组给予虎杖提取物133 mg/kg,芎芍胶囊55 mg/kg;洛伐他汀组给予洛伐他汀3.3 mg/kg;血脂康组给予血脂康0.2 g/kg;以上药物根据剂量蒸馏水溶解,混匀后灌胃,每次0.4 mL。模型组、普通饲料组、C57BL/6J小鼠对照组均灌服生理盐水0.4 mL。用药17周后,下腔静脉取血,全自动酶标仪检测血清hs-CRP浓度。结果 模型组血清hs-CRP水平显著高于正常对照组和普饲组（P<0.05,P<0.01）;各给药组中,洛伐他汀组、解毒组和配伍高剂量组hs-CRP水平下降,与模型组比较,差异有统计学意义（P<0.01）;配伍高剂量组hs-CRP水平低于洛伐他汀组、血脂康组、单纯解毒或活血组及配伍中、低剂量组;解毒组hs-CRP水平低于活血组（P<0.01）。结论 解毒活血配伍方药可降低ApoE( / )小鼠血清hs-CRP水平。     

波动性高血糖与心血管并发症关系

2型糖尿病是冠心病的等危症,内皮功能异常是糖尿病心血管并发症发生发展的重要病理生理基础。除高血糖可导致内皮功能损伤外,波动性高血糖具有更为明显的作用,包括促进内皮细胞凋亡,诱导氧化应激,增加细胞间黏附分子合成等。对血糖波动的正确认识、评价和治疗可能对糖尿病合并心血管并发症的研究具有重要意义。     

西洋参茎叶总皂苷对胰岛素抵抗脂肪细胞葡萄糖转运、GLUT-4转位和CAP基因表达的影响

目的观察西洋参茎叶总皂苷(PQS)对脂肪细胞胰岛素抵抗状态下葡萄糖转运、葡萄糖转运子-4(GLUT-4)转位和c-cb1结合蛋白(CAP)基因表达的影响。方法将3T3-L1前脂肪细胞诱导分化为成熟脂肪细胞,用游离脂肪酸(FFA)制备脂肪细胞胰岛素抵抗(IR)模型,液闪仪测定3H标记的葡萄糖的摄取率,免疫荧光法检测GLUT-4转位,用逆转录-聚合酶链反应(RT-PCR)法检测培养细胞中CAPmRNA的表达。结果模型组胰岛素刺激下的葡萄糖转运率明显低于正常对照组(P<0.01);与模型组相比,二甲双胍组、PQS大/中剂量组葡萄糖转运率明显增加(P<0.01、P<0.01、P<0.05),但PQS小剂量组作用不明显。正常对照组在胰岛素刺激前,GLUT-4大部分位于胞质内,胰岛素刺激30min后,胞质内的分布较刺激前明显减少,胞膜周围的分布相对增加;而模型组在胰岛素刺激前后,GLUT-4在细胞内的分布无变化;但在二甲双胍组和PQS3个剂量组的结果显示,胰岛素刺激后,胞质内GLUT-4分布减少,胞膜周围的分布相对增加。模型组CAPmRNA水平较正常组明显下降(P<0.05);与模型组相比,二甲双胍和PQS大、中剂量组CAPmRNA水平明显上升(P<0.01),PQS小剂量未见明显效果。结论PQS可改善脂肪细胞IR,这可能与其促进脂肪细胞CAP基因转录、GLUT-4转位和葡萄糖转运有关。     

西洋参茎叶总皂苷对脂肪细胞糖脂代谢及胰岛素抵抗信号转导的影响

目的观察西洋参茎叶总皂苷(panax quinquefolius saponin,PQS)对脂肪细胞糖脂代谢及胰岛素抵抗信号转导的影响。方法将3T3-L1前脂肪细胞诱导分化为成熟脂肪细胞,用游离脂肪酸(FFA)制备脂肪细胞胰岛素抵抗(IR)模型,再加入相应药物作用,最后用葡萄糖氧化酶法检测药物作用后脂肪细胞培养液中葡萄糖消耗量,用比色法检测药物对肿瘤坏死因子-α(TNF-α)的脂解作用的影响,用Western-blot法检测胰岛素刺激后信号蛋白磷酸化水平。结果模型组葡萄糖消耗量(mmol/L)为5.250±2.671,显著低于对照组14.133±1.305(P0.01);与模型组相比,二甲双胍组(1 mmol/L及PQS大、中、小剂量组(0.08、0.04、0.02 mg/mL)葡萄糖消耗量均显著增加(P0.01),分别为11.807±1.358、10.784±2.373、10.217±1.237、9.984±2.006,且随着PQS用药剂量的增加,葡萄糖消耗量也逐渐增加。TNF-α组培养液中FFA浓度(nmol/μg)(2.479±0.597)显著高于对照组(1.320±0.538)(P0.01);与TNF-α组相比,二甲双胍及PQS大、中、小剂量组培养液中FFA浓度均显著降低(P0.01),分别为1.210±0.566、1.105±0.631、1.108±0.260、1.201±0.593,且随着PQS用药剂量的加大,其抗脂解作用逐渐增强。模型组胰岛素受体β亚单位、IRS-1酪氨酸磷酸化水平及PKB的Ser473磷酸化水平均较对照组减低;与模型组比较,PQS小剂量组信号蛋白磷酸化水平无明显变化,但PQS中、大剂量和二甲双胍组信号蛋白磷酸化水平均有不同程度增高的趋势。结论PQS能够促进脂肪细胞利用葡萄糖、抑制TNF-α的促脂解作用,从而调节糖脂代谢。PQS调节糖脂代谢的作用可能与其促进脂肪细胞胰岛素信号转导、改善胰岛素抵抗有关。     

冠心病稳定期因毒致病的辨证诊断量化标准

现代中医学认为,血瘀是冠心病发生发展过程的一个主要病机,但冠心病急性心血管事件发生所表现的临床表征和病理变化,似非单一“血瘀” 病因病机所能概括。根据传统中医学因毒致病特点的认识,冠心病急性心血管事件发生当存在因毒致病或“瘀”、“毒”从化互结致病的病因病机。利用临床流行病学方法,制订符合循证医学理念的冠心病因毒致病的辨证诊断及量化标准,对早期识别冠心病高危人群,促进中医在冠心病防治领域发挥既病防变相关干预措施的优势,提高临床疗效,具有重要意义。     

Effect of chinese herbal drug-containing serum for activating-blood and dispelling-toxin on ox-LDL-induced inflammatory factors’ expression in endothelial cells

<正>Objective:To investigate the effects of drug-containing serum of Chinese herbal compound, Xiongshao Capsule(芎芍胶囊,XS,for activating-blood) and Huanglian Capsule(黄连胶囊,HL,for dispellingtoxin) on the oxidized low-density lipoprotein(ox-LDL)-induced inflammatory factors in human umbilical vein endothelial cells(HUVECs).Methods:Thirty-two rats were randomly divided into four groups:the blank control group treated with distilled water,the positive control group treated with simvastatin(1.8 mg/kg),the test group I treated with Chinese herbal compound of XS(0.135 g/kg),and the test group II treated with Chinese herbal compound of XS(0.135 g/kg) and HL(0.135 g/kg).All the treatments were administered for 7 successive days by gastrogavage.Rats' blood serum was harvested 1 h after the last administration to prepare respective drugcontaining serum.HUVECs were exposed to ox-LDL(100μg/mL) to induce cell injury model and incubated with corresponding drug-containing serum for 24 h.Untreated HUVECs were set for blank control.Levels of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),and soluble intercellular adhesion molecule-1(slCAM-1) in supernatant of cultured HUVECs were determined by enzyme-linked immunosorbent assay(ELISA).HUVEC surface expressions of ICAM-1 and E-selectin were determined by flow cytometry.Results:Levels of IL-6, TNF-α,and slCAM-1 in the supernatant of HUVECs as well as the cell surface expressions of ICAM-1 and E-selectin significantly increased after 24-h ox-LDL stimulation(P0.01),while the abnormal elevations,except slCAM-1 in the test groupⅠ,were all reduced in the treated groups(the positive control and the two test groups) significantly(P0.01 or P0.05).Besides,the effect in the test group II seemed somewhat higher than that in the test group I but with no statistical significance(P0.05).Conclusion:Drug-containing serum of XS plus HL has a certain inhibitory effect on the vascular endothelial inflammation response induced by ox-LDL.     

p38MAPK信号通路与内皮细胞激活

内皮细胞激活是内皮细胞损伤的始动因素,是引起各种不同程度的炎症反应和细胞凋亡的前提条件 ;丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK) 是哺乳动物细胞中重要的信号转导通路,其中 p38MAPK 通路在细胞应激、细胞生长、凋亡和炎症等多种生理和病理过程中起重要作用,越来越引起业界的广泛关注,本文就 p38MAPK 信号通路及其与内皮细胞激活的相关性做一综述,旨在进一步对内皮细胞损伤引发心血管疾病研究提供参考资料。     

Effects of Propyl Gallate on adhesion of polymorphonuclear leukocytes to human endothelial cells induced by tumor necrosis factor alpha

Objective:To investigate the effects of Propyl Gallate(PrG) on cellular adhesion between human umbilical vein endothelial cells(HUVEC) and polymorphonuclear leukocytes(PMN) as well as the expression of intercellular adhesion molecule-1(ICAM-1,CD54) and E-selectin(CD62E) on the VEC surface.Methods: A human VEC inflammation model was induced by tumor necrosis factor alpha(TNF-α).VECs were preincubated with varying concentrations of PrG(0.001-5 mmol/L) or 1‰DMSO(v:v) or 10 mmol/L acetylsalicylic acid(ASA) f...     

Effects of active components of Red Paeonia and Rhizoma chuanxiong on angiogenesis in atherosclerosis plaque in rabbits

Objective： To investigate the effects and mechanism of the active components of Red Paeonia and Fthizoma chuanxiong （Xiongshao Capsule, 芎芍胶囊, XSC） on angiogenesis in atherosclerosis plaque in rabbits. Metbods： Fifty New Zealand rabbits were randomly divided into the normal group, the model group, and the three medicated groups treated respectively with Simvastatin （2.5 mg/kg per day）, low-dose （0.24 g/kg per day） and high-dose （0.48 g/kg per day） XSC, 10 in each group. Rabbits in the normal group were fed with regular diet. To those in the other four groups, high fat diet was given, and a balloon angioplasty was performed two weeks later to establish abdominal aortic atherosclerosis model. Then, the model rabbits were fed continuously with high fat diet, and to those in the medicated groups, the testing drugs were added in the forage correspondingly for 6 successive weeks. Levels of blood lipids were measured at the end of the experiment. Meantime, serum levels of high sensitivity C-reactive protein （hsCRP） and tumor necrosis factor α （TNF-α） were detected with enzyme-linked immunoassay; the plaque area （PA）, cross-sectional vascular area （CVA） and correcting plaque area （PNCVA） were determined quantitatively using imaging software; and the protein expression of vascular endothelial growth factor （VEGF） and factor Ⅷ related antigen （FⅧRAg） in plaque was detected using immunohistochemical method. Results： As compared with the model group, the content of total cholesterol （TC） in the three medicated groups, and contents of triglyceride （TG） and low-density lipoprotein cholesterol （LDL-C） in the Simvastatin group were lower to various extents （P〈0.05, P〈0.01）. The serum level of hsCRP in all modeled rabbits was higher than that in the normal group, but in the three treated groups it was significantly lower than that in the model group （P〈0.05, P〈0.01）. Expressions of VEGF and FⅧRAg, as well as PNCVA in the three medicated groups were significantly lower than those in the model control group （P〈0.05, P〈0.01）. Conclusion： The active components of Red Paeonia and Rhizoma chuanxiong have definite effects in delaying the genesis and development of atherosclerosis, its mechanism might be related with the inhibition on angiogenesis in plaque, and also with its actions of lipo-metabolism regulation and anti-inflammation.