Interaction of C-reactive protein with artificial phosphatidylcholine bilayers.

C-Reactive protein (CRP), the most characteristic of the 'acute phase proteins' (ref. 1) is thought to participate in the mediation and/or modulation of acute inflammatory processes, but its exact function is unknown. CRP has a Ca2+-dependent binding specificity for phosphorylcholine, the polar head group of two widely distributed lipids, lecithin (phosphatidylcholine, PC) and sphingomyelin (SM). A number of observations suggest that at least some of the biological activities of CRP depend on its interaction with phospholipids of cell membranes. In addition, interaction of CRP with PC- and SM-containing lipid dispersions and with PC-containing liposomes can activate the complement system. We report here that binding of CRP to model membranes of PC requires the incorporation into the bilayer of lysophosphatidylcholine (LPC). Thus, a disturbance of the molecular organisation of the bilayer appears to be necessary for binding of CRP. These findings provide a possible biochemical explanation for binding of CRP to damaged but not intact cell membranes and might be relevant to its biological function.     

Regulated conformation changes in C-reactive protein orchestrate its role in atherogenesis

C-reactive protein (CRP) is a prototypic human acute phase reactant composed of five identical subunits. Emerging evidence indicates that CRP is not merely a predictor of cardiovascular disease, but may also be a direct mediator. However, the diverse and sometimes contradictory activities of CRP have considerably hampered the attempts to define the exact role of CRP in atherogenesis. Here, we review the multiple layers of regulation of CRP’s structure and function, highlighting how local inflammation conditions, such as the abundance of damaged cell membranes and redox homeostasis, can tip the balance of the pro-and antiinflammatory activities of CRP. We propose that the highly controlled interplay between different structural conformations of CRP underlies its intrinsic property as a fine modulator of inflammation and atherogenesis.     

N，N'-二芳基-吡啶二甲酰胺和N，N’-双-吡啶甲酰胺烃类配体的合成及其结构表征’

合成了含N,N’-二芳基-吡啶二甲酰胺和N,N’-双-吡啶甲酰胺烃类的九种配体,它们的结构经UV,MS,IR,1HNMR及元素分析所确证.比较了两种合成方法的优缺点,并对合成条件作了探索.     

川芎生物碱对大鼠脑缺血-再灌注损伤的保护作用

目的探讨川芎(CHX)生物碱对大鼠脑缺血-再灌注(I/R)损伤的保护作用.方法取Wistar大鼠60只,随机分成6组,每组10只,即假手术组、I/R模型组、川芎生物碱低中高剂量治疗组和阳性药葛根素(GGS)组.采用线栓法建立大鼠大脑中动脉可逆性脑I/R病理损伤模型,用黄嘌呤氧化酶法和硫代巴比妥酸显色法测定脑组织中超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量.动物苏醒后进行神经功能损伤评分,检测脑组织含水量及容积的变化,同时与假手术组进行比较.结果 I/R实验组与注射生理盐水假手术组比较,脑组织中SOD的活性显著降低,MDA的含量明显增加(P0.01),脑梗死面积和容积明显增大(P0.01),脑组织含水量增多,神经功能损伤较重(P0.05).CHX生物碱治疗组与I/R组比较,脑组织中的SOD的活性显著升高(P0.01),MDA的含量明显降低(P0.05),脑组织含水量减少,脑梗死容积明显缩小(P0.01),神经功能损伤评分差异显著(P0.01).结论 CHX生物碱可减轻大鼠脑I/R引发的脑损伤程度,从而对脑组织具有一定的保护作用.     

血清C反应蛋白水平与急性脑梗死病情及预后的关系

目的探讨急性脑梗死患者血清C反应蛋白（CRP）水平的变化与病情严重程度及其预后的关系。方法分别测定大动脉粥样硬化性脑梗死患者（LAA组）78例、腔隙性脑梗死患者（LCI组）36例和健康体检者（对照组）40例血清CRP含量,并进行比较。按脑卒中患者临床神经功能缺损程度评分（NDS）标准对患者进行评分。结果LAA组CRP含量高于LCI组,LCI组高于对照组（P〈0．05）;IAA组中,CRP异常率高于LCI组（P〈0．05）,CRP异常的患者NDS评分的改善低于CRP正常组,且CRP异常者预后中无变化者高于正常对照组（P〈0．01）。结论CRP水平增高与脑梗死的发生和严重程度预后有密切关系。     

大鼠急性心肌梗塞后在不同部位移植胚胎干细胞疗效研究

目的探讨大鼠急性心肌梗塞（AMI）后在不同部位移植胚胎干细胞（ESC）的心肌组织形态学及血液动力学变化。方法Wistar大鼠40只随机分为正常对照组、梗塞未治疗组（梗塞组）、梗塞中心移植组（中心组）、梗塞周边移植组（周边组）共4组。结扎冠状动脉左前降支制成急性心肌梗塞模型,梗塞后1周移植体外分化并经标记的ESCs,移植后4周分别检测组织形态及血流动力学指标的改变。结果周边组移植细胞稳定存活,而中心组移植细胞未能存活。心功能及组织学检测表明中心组与梗塞组无显著差异（P〉0．05）;与梗塞组比较,周边组梗塞面积显著小于梗塞组（P〈0．01）,（21．0±1．3）％VS（40．7±2．2）％;左室重量小于梗塞组（P〈0．01）,（702．0±24．0）nagVS（882．2±32．6）mg;反应左室收缩功能的指标左室内压最大上升速率和左室内压均大于梗塞组（P〈0．01）,分别为（7．9±0．7）X103mmHg／sVS（5．9±0．5）×103mmHg／s和（117．5±10．7）mmHgVS（89．24-8．1）mmHg;而左室舒张末期压力均明显小于梗塞组（P〈0．01）,（8．5±0．3）mmHgV8（13．6±1．2）mmI-Ig。结论梗塞周边区移植ESCs可以阻止心室重构、减少瘢痕面积、改善心功能。     

乙炔基对苯腈取代芘衍生物光电性质的影响

采用密度泛函理论DFT/B3LYP等方法研究了乙炔基对苯腈取代芘衍生物1,6-二(4-氰基苯基)芘的结构和光电性质的影响.结果表明,1,6-二(2-(4-氰基苯基)乙炔基)芘的分子结构具有高度平面性,电子激发对该化合物的结构几乎无影响.与1,6-二(4-氰基苯基)芘相比,由于乙炔基的引入,1,6-二(2-(4-氰基苯基)乙炔基)芘的热力学稳定性提高,电子注入传输性能增强,能隙减小,光谱红移,且易于分子聚集发生,其不仅有望成为掺杂型发光材料,还有可能是潜在的电子型材料.     

Early association of electrocardiogram alteration with infarct size and cardiac function after myocardial infarction

OBJECTIVE: Myocardial infarction (MI) is the main cause of heart failure, but the relationship between the extent of MI and cardiac function has not been clearly determined. The present study was undertaken to investigate early changes in the electrocardiogram associated with infarct size and cardiac function after MI. METHODS: MI was induced by ligating the left anterior descending coronary artery in rats. Electrocardiograms, echocardiographs and hemodynamic parameters were assessed and myocardial infarct size was measured from mid-transverse sections stained with Masson's trichrome. RESULTS: The sum of pathological Q wave amplitudes was strongly correlated with myocardial infarct size (r = 0.920, P < 0.0001), left ventricular ejection fraction (r = -0.868, P < 0.0001) and left ventricular end diastolic pressure (r = 0.835, P < 0.0004). Furthermore, there was close relationship between MI size and cardiac function as assessed by left ventricular ejection fraction (r = -0.913, P < 0.0001) and left ventricular end diastolic pressure (r = 0.893, P < 0.0001). CONCLUSION: The sum of pathological Q wave amplitudes after MI can be used to estimate the extent of MI as well as cardiac function.     

极化液对大鼠不同血糖浓度下心肌缺血再灌注的影响

目的:探讨不同血糖浓度下大鼠心肌缺血再灌注(MI/R)心肌损伤的程度及明确极化液(GIK)对高血糖心肌MI/R的保护作用.方法:将12只健康SD大鼠,随机分为4组,每组3只,即对照组、GIK组、高血糖组、GIK+高血糖组.每组大鼠结扎左冠状动脉前降支30 min,再灌注120 min.采用氯化三苯基四氮唑(TTC)染色法检测大鼠缺血再灌注心肌的心肌梗死面积.动态观察Ⅱ导联心电图QRS波、T波、ST段和心率变化.结果:TTC染色显示每组大鼠心肌都有梗死,心肌梗死面积高血糖组>GIK+高血糖组>对照组>GIK组;心电图显示高血糖大鼠心肌缺血期ST段明显抬高,再灌注后实验动物出现心律失常.GIK对正常血糖大鼠MI/R具有明显保护作用.结论:GIK对高血糖大鼠心肌缺血再灌注损伤保护作用有限,而对正常血糖大鼠MI/R损伤有较好的保护作用.     

C反应蛋白与急性冠脉综合症的相关性及PCI术后的变化

探讨C反应蛋白(CRP)水平与急性冠脉综合征的相关性及行经皮冠状动脉介入治疗(PCI)术后的变化。采用酶联免疫吸附试验(ELISA)法测定经冠状动脉造影确诊的57例冠心病患者及28例冠状动脉造影正常者的血清CRP水平,并比较16例行PCI术的患者术前、术后的血清CRP水平变化。血清CRP在急性心肌梗死组(15.74±1.62)mg/L明显高于不稳定型心绞痛组(11.35±2.52)mg/L,且两者明显高于稳定型心绞痛组(4.68±2.61)mg/L和正常对照组(2.68±1.16)mg/L,(P<0.01)。同时冠心病患者PCI术后血清CRP水平明显高于术前。CRP水平与ACS的临床类型密切相关,可以作为判断ACS预后的指标;PCI能导致冠心病患者的内皮损伤,加重炎症反应,可能是引起管腔内再狭窄的因素。     

血清CK,CRP的测定对急性心肌梗死的诊断价值

目的 探讨血清肌酸激酶CK,C－反应蛋白（CRP）对急性心肌梗死的辅助诊断价值。方法 CK采用酶动力学方法测定,CRP采用免疫琼脂扩散方法测定。结果 CK在心肌梗死2h后有明显升高,6h后仍为阳性,CRP在发作2h后质量浓度明显高于正常人。结论 同时检测血清CK、CRP对急性心肌梗死有诊断价值。     

有氧间歇训练对心肌梗死大鼠心肌细胞的增殖作用及相关机制

目的:通过建立SD大鼠心肌梗死模型,观察间歇训练对心梗大鼠心肌细胞的增殖作用并探讨其内在作用机制.方法:成年雄性SD大鼠40只,造模后,随机分为3组:假心梗组(CON);心梗组(MI);心梗+间歇训练组(MI+AIT),每组12只.间歇训练共计8周.结果:免疫组化结果提示,正常心肌组织鲜见细胞增殖现象;心肌梗死可造成梗死边缘区细胞代偿性增加;间歇训练可显著性增加细胞增殖核抗原PCNA,BrdU和ki-67的表达水平.另外,心梗还可引起细胞增殖核抗原调节蛋白p70S6K及其上游调节蛋白mTOR显著性降低(P<0.05);而mTOR的上游调节蛋白PI3K,Akt也具有相似的变化趋势.相对地,间歇训练可增加心肌细胞膜IGF-R1水平(非IGF-R2),上调PI3K-AKt-mTOR信号通路活性,增加p70S6K磷酸化水平(P<0.05).结论:间歇训练介导的细胞增殖作用与其上调IGF-R1表达水平,激活细胞PI3K-Akt介导的增殖通路相关.     

ASA治疗对急性缺血性脑血管病微栓子及颈内动脉粥样硬化斑块的影响

目的以脑动脉系统微栓子及斑块为指标,探讨ASA(抗血小板药物、他汀类药物、抗高血压药物)治疗方案对急性脑梗死患者的治疗效果.方法选取经MRA或CTA证实、MES检出为阳性的急性脑梗死患者70例,分为对照组和治疗组,每组各35例.对照组给予改善循环和营养神经的药物治疗,治疗组在对照组基础上加ASA治疗,分别比较两组患者第3,6,9天微栓子(MES)数量和阳性率,同时比较斑块变化情况.结果 ASA治疗组比常规治疗组栓子下降率高,且随治疗时间的延长,其下降率之差增加,第9天时差异具有统计学意义(P0.05);ASA组斑块减小的更多.结论 ASA治疗可有效减小斑块的大小,减少微栓子的脱落,从而控制脑梗死的进展.     

三七总皂苷对心梗后心室重构大鼠增强抗氧化与改善心肌形态学作用

 为研究三七总皂苷(PNS)对急性心肌梗塞（AMI）后左室重构（LVRM）大鼠自由基损伤和心肌细胞形态学改变的作用, 采用结扎大鼠左冠状动脉前降支的方法,建立AMI模型,术后24 h后随机分为对照组和实验组,连续4周分别灌胃给予生理盐水和PNS低、中、高剂量,观察PNS和福辛普利对病鼠血清丙二醛（MDA）、c反应蛋白(CRP)、肌红蛋白-I（cTn-I）及肌酸激酶同工酶（CK-MB）、谷胱甘肽过氧化物酶（GSH-Px）、一氧化氮（NO）及心肌细胞形态病理结构和心脏指数改变等的影响。结果发现与对照组比较,PNS与福辛普利均能显著改善病鼠左室心肌细胞形态结构病理改变及心脏指数（P<0.01）,显著降低MDA、CRP、CK-MB与cTn-I、提高GSH-Px活性（P<0.01～0.05）,高剂量PNS可明显降低NO含量（P<0.05）。可见PNS可通过抑制脂质过氧化反应,减轻病鼠心肌细胞的病理损伤,增强抗氧化,具有抑制心肌肥大与改善心室重构心肌细胞形态学结构作用。     

黄精多糖对急性心肌梗死模型大鼠炎症及氧化应激反应的影响

摘要: 目的探讨黄精多糖( PSP) 对急性心肌梗死模型( AMI) 大鼠损伤的保护作用及可能机制。方法采用结扎冠状动脉左前降支的方法制备心肌梗死动物模型,假手术组只穿线不结扎,将造模成功的大鼠随机分为模型组、黄精多糖高、中、低剂量组( 900 mg /kg、450 mg /kg、225 mg /kg) 及阳性组( 麝香保心丸, 12. 2 mg /kg·d) ,每组10 只,每日灌胃1 次,连续4 周。分别记录造模前、造模即刻及给药1、3、7、10、14、21、28 d 心电图S-T 段变化,采用酶联免疫吸附法( ELISA) 测定各组大鼠血清中肿瘤坏死因子α( TNF-α) 、白介素6( IL-6) 、谷胱甘肽过氧化物酶( GSH-Px) 及丙二醛( MDA) 含量; 显微镜下观察受损心肌病理学的改变。结果与模型组相比,黄精多糖能明显抑制心肌梗死模型大鼠S-T 段的升高; 各给药组大鼠血清IL-6、TNF-α 水平均显著降低( P ＜ 0. 05 或0. 01) ,GSH-Px 活性升高( P ＜ 0. 05或0. 01) ,并降低MDA 含量( P ＜ 0. 05 或0. 01) ,心肌损伤程度明显改善。结论PSP 对急性心肌梗死模型大鼠心肌损伤有保护作用,其作用机制可能与减轻炎症反应,提高氧自由基清除能力,减少脂质过氧化损伤有关。     

Therapeutic induction of angiogenesis by direct myocardial administration of an adenovirus vector encoding human hepatocyte growth factor gene and its safety

After the study in vitro and in rats, we assessed further the effects and safety of local angiogen therapy using intramyocardial delivery of an adenovirus carrying hepatocyte growth factor gene (Ad-HGF) in a canine ischemia model. The angiogenic activity of Ad-HGF was evaluated from three aspects. First, the augmentation of collateral vessel development was assessed by angiography 30 d after surgery. The results showed that the density of collateral vessels in treated group was higher than that of control group. Secondly, infarct size was evaluated by TTC staining and image analysis. The results showed that the infarct size of treated group was smaller than that of control group. Thirdly, the myocardial regional blood flow was determined by the method of colored microspheres. The results showed that the blood flow recovered to the level before ligation in treated group, but that of the control group was lower than normal level. In addition, during the study of chronic toxicity, we tested the anti-adenovirus antibodies by neutralization method. The antibodies yielded after the fourth injection decreased slowly from peak level and disappeared 12 weeks after drug withdrawal. Overall, Ad-HGF can promote angiogenesis in ischemic myocardium and reduce infarct size. So this method may be considered as a therapeutic angiogenesis induction strategy for ischemic disease including myocardial infarction and peripheral artery disease. At the same time, Ad-HGF could induce the yield of anti-adenovirus antibodies to neutralize adenovirus, which may be the mechanism of adenovirus clearance.     

双水杨醛缩1,6-己二胺Schiff碱铜配合物改性UHMWPE新型耐磨材料的研究

分别对含不同质量分数(2.5wt％、5wt％、10wt％、15wt％)的双水杨醛缩二胺型Schiff碱Cu(Ⅱ)配合物的改性UHMWPE与45#钢配副进行了干摩擦条件下的销-盘摩擦磨损试验,并采用SEM观察试样磨损表面形貌,采用EDS分析销试样未磨损及磨损表面的主要元素组成,探讨其磨损机理.结果表明:在15wt％质量分数范围内,随着双水杨醛缩1,6-己二胺Schiff碱铜配合物添加量的增加,改性UHMWPE与钢配副的摩擦系数逐步降低,耐磨性逐步提高,其中磨损最轻的是含10wt％双水杨醛缩1,6-己二胺Schiff碱Cu(Ⅱ)配合物的改性UHMWPE;磨损机制均为磨粒磨损,并发现Schiff碱Cu(Ⅱ)配合物添加剂中的Cu元素发生了选择性转移效应.     

含有环丙沙星高分子前药物的合成

以抗菌药物-盐酸环丙沙星（CIPRO）代替传统的聚氨酯扩链剂,采用六亚甲基二异氰酸酯（HDI）、聚己内酯（PCL）为原料,通过典型的两步聚氨酯缩合反应,成功地将药物耦合到聚氨酯的骨架结构上,合成了环丙沙星-聚氨酯高分子前药物。研究了不同加料顺序对药物含量和平均分子量的影响。结果表明,合成的高分子前药物具有较高的药物含量、平均分子量和较窄的分散性。     

Localization of D-2 dopamine receptors to intrinsic striatal neurones by quantitative autoradiography

Recent work with positron emission and single photon emission computed tomography has demonstrated the feasibility of studying striatal dopamine receptors in the living human brain. For the proper interpretation of these studies in normal and diseased states, the cellular localization of these receptors must be definitively established. It has been claimed, on the basis of receptor binding studies with tissue homogenates in rats, that 30-50% of striatal D-2 dopamine receptors are located on axons or terminals of the corticostriatal pathway. This finding has been incorporated into major reviews and classifications of dopamine receptors. The recent development of quantitative autoradiographic methods for diffusible ligands has facilitated the study of neurotransmitter receptors in cytoarchitechtonically intact tissue. Because this technique provides the necessary anatomic resolution that is lacking in homogenate binding studies, we have used it to re-examine the localization of striatal dopamine receptors. Here we present evidence that D-2 receptors are located exclusively on kainic acid-sensitive intrinsic neuronal elements in the striatum. We report that discrete cortical ablation does not alter 3H-spiperone binding to rat striatum and thus our results do not support the existence of D-2 dopamine receptors on the terminals of the corticostriatal pathway.     

中场强磁共振机弥散加权成像诊断超急性期脑梗塞（附8例分析）

目的：评价中场强机MRI弥散加权像（DWI）用于诊断超急性期脑硬塞的价值。方法：8例发病时间在4-6h内的超急性期脑梗塞者接受了DWI检查,分析其图像特征及病灶检出率,所有患者同时进行了CT平扫与MR常规序列检查,并此后3d-1周内完成复查,作为影像学对比。结果：8例中通过DWI检出发病4-6h超急性期大脑中动脉梗塞4例,右背侧后丘脑伴同侧枕叶梗塞1例,双枕顶叶深部梗塞1例,脑干梗塞1例,左侧小脑半球梗塞1例,并通过随诊检查得以证实,其敏感性和特异性均为100%;同期MRI常规序列检出右侧大脑中动脉梗塞1例,另有1例不能确定诊断;同组中,CT未能检出该病灶。三者间存在显著性差异。结论：DWI在超急性期脑梗塞诊断中具有重要价值,是超急性期脑梗塞的首选检查方法。