目的 观察时间窗内重组组织型纤溶酶原激活剂(rt-PA)静脉溶栓联合依达拉奉治疗急性脑梗死的效果.方法 将我院收治的82例急性脑梗死患者根据随机数字表法分为观察组(41例,rt-PA静脉溶栓联合依达拉奉)和对照组(41例,rt-PA静脉溶栓).比较两组的治疗效果.结果 治疗后,观察组的美国国立卫生研究院卒中量表(NIHSS)评分低于对照组,脑卒中专用生活质量量表(SS-QOL)评分高于对照组(P<0.05).观察组的治疗总有效率高于对照组(P<0.05).治疗后,观察组的丙二醛(MDA)、基质金属蛋白酶-9(MMP-9)、纤维蛋白原(Fib)、D-二聚体、血栓素B2(TXB2)、内皮素-1(ET-1)水平低于对照组,超氧化物歧化酶(SOD)、一氧化氮(NO)水平高于对照组,活化部分凝血活酶时间(APTT)长于对照组(P<0.05).结论 时间窗内rt-PA静脉溶栓联合依达拉奉治疗急性脑梗死的效果显著,可以改善患者的氧化应激水平、凝血功能和内皮功能指标.

OBJECTIVE:The aim of this study was to examine the effect of TXL, a Chinese medicine prescription, on cerebral microcirculatory disturbances after pMCAO in mice using TPLSM and further explore the underlying mechanisms.METHODS:Adlut male C57BL/6J mice were subjected to pMCAO and orally administered with TXL (3.0, 1.5 and 0.75 g/kg/d) at 1, 3, and 21 hours after pMCAO. The following parameters were examined at 6 and 24 hours after pMCAO: neurological deficits, infarct volume, BBB permeability, cerebral microvessel structure, brain microcirculation (TPLSM imaging), vasoactive factors, and adhesion molecules.RESULTS:TXL improved neurological deficits, reduced infarct volume, attenuated BBB disruption, protected cerebral microvessel structure, increased cerebral capillary flow velocity and volume flux, and inhibited leukocyte-endothelial cell interactions at 6 or 24 hours after pMCAO. The therapeutic efficacy was exerted in a dose-dependent manner. Further study revealed that TXL (high dose) regulated the expression of PGI2, TXA2, and ET-1, and suppressed ICAM-1 and P-selectin.CONCLUSIONS:TXL alleviates cerebral microcirculatory disturbances against ischemic injury by modulating endothelial function and inhibiting leukocyte-endothelial cell interactions. These effects are associated with regulating the expression of PGI2, TXA2, and ET-1, and suppressing ICAM-1 and P-selectin expression.

Micro-angiogenesis in the arterial wall has been observed during the development and progression of atherosclerosis. The aim of the present study was to examine whether inflammation, oxidative stress and hypoxia are involved in the process of early atherosclerotic micro‑angiogenesis. A total of 24 rabbits were randomly divided into a normal diet group or a high‑cholesterol (HC) diet group and were fed the corresponding diets for 4 weeks. The microvessel density (MVD), level of hypoxia and the levels of inflammatory markers and antioxidants in the arterial wall were detected using immunohistochemical and molecular biological techniques, respectively. The present results demonstrated that the MVD in the HC group was significantly higher (P<0.01) than that observed in the rabbits, which were provided with a normal diet, while hypoxia‑inducible factor‑1α levels did not exhibit marked changes in either of the two groups (P>0.05). The levels of inflammatory markers and antioxidants were significantly different between the two groups (P<0.05). The present study demonstrated that the primary factors, which promote micro‑angiogenesis are possibly associated with an increase in inflammation and a decrease in the levels of antioxidants, as tissue hypoxia in the arterial wall at this stage was not evident.

Objective:To investigate the antioxidant effect of bioactive substances from tsao-ko in the aged ICR mice induced by D-galactose. Methods:Aged mice induced by high fat diet and D-galactose were feeding separately with different kinds of diets. High dose of tsao-ko was 200mg/kg,low dose of tsao-ko was 100mg/kg.The level of SOD,GSH,GSH-Px,MDA and 8-ISO-PGF2α in plasma,liver was investigated in aged mice in the experiment of the antioxidant activity in vivo. Results:Compared with the control group about the data of plasma,the activity of SOD in the aged mice conducted with tsao-ko was significantly improved(p0.01),the content of GSH of mice deposed with tsao-ko was significantly improved(p0.01),the activity of GSH-Px in the aged mice conducted with high dose of tsao-ko was significantly improved(p0.01),the content of MDA in the aged mice conducted with tsao-ko was lower(p0.05),the content of 8-ISO-PGF2α in the aged mice conduced with high doses of tsao-ko was lower(p0.05). Compared with the control group about the data of liver,the activity of SOD of mice conducted with low dose of tsao-ko was improved(p0.05) and significantly improved with high dose(p0.01),the content of GSH in the aged mice conducted with high dose of tsao-ko was significantly improved(p0.01),the activity of GSH-Px of mice conducted with tsao-ko was improved significantly(p0.01),the content of MDA in the aged mice conducted with tsao-ko was lower significantly(p 0.01). Conclusion:The methanol extract of tsao-ko could increase the level of SOD,GSH,GSH-Px and reduce MDA and 8-ISO-PGF2α.

目的 观察通心络胶囊对血管舒张功能及动脉粥样硬化的影响.方法 将240只新西兰兔随机分为正常组、模型组、阿托伐他汀组和通心络高、中、低剂量组,每组40只.正常组给予普通饲料喂养,其余各组均给予高脂饲料喂养建立高脂血症模型,在造模同时阿托伐他汀组给予阿托伐他汀溶液2.5 mg/kg灌胃,通心络高、中、低剂量组分别给予通心络胶囊溶液0.6、0.3、0.15 g/kg灌胃,灌胃体积均为3 ml/kg,每日1次.分别于实验后第3天、1周、2周、4周、6周检测各组血脂水平、主动脉管壁微血管密度及主动脉内皮依赖性舒张功能变化,并对血管舒张功能与管壁微血管密度进行相关性分析.结果 通心络高、中剂量组和阿托伐他汀组均能有效降低总胆固醇、甘油三酯和低密度脂蛋白水平(P ＜0.05或P＜0.01);与模型组比较,阿托伐他汀组和通心络高剂量组在给药4周、6周时主动脉舒张率明显升高,管壁微血管密度降低(P ＜0.05或P＜0.01),通心络中剂量组在给药6周时主动脉舒张率也升高,管壁微血管密度降低(P＜0.05);内皮依赖性血管舒张功能与管壁微血管密度呈负相关(r=-0.824,P＜0.01). 结论 通心络胶囊通过降低血脂水平、抑制动脉管壁微血管的滋生,来改善血管舒张功能,从而延缓动脉粥样硬化的进一步发展.

目的 观察高脂血症对兔动脉管壁微血管血流量及氧供的影响.方法 将20只雄性新西兰兔随机分为正常对照组和高脂饮食组,每组10只,正常对照组饲喂普通饲料,高脂饮食组饲喂高脂饲料,实验4周时留取血流样本及主动脉组织样本,采用全自动生化分析仪测量其血脂四项水平,彩色微球技术测量其主动脉管壁微血管血流量,免疫组织化学染色观测其管壁微血管密度及缺氧诱导因子1 α(HIF-1α)阳性表达,实时荧光定量逆转录聚合酶链反应(RT-qPCR)和Western blot测定动脉组织中HIF-1α的mRNA表达及蛋白水平.结果 高脂饮食组血脂四项水平均显著高于正常对照组(P＜0.01);高脂饮食组主动脉管壁微血管血流量较正常对照组明显增加[58.56±6.21 μL/(min·g)比39.17±4.47 μL/(min·g),P＜0.01];高脂饮食组主动脉管壁微血管密度也显著高于正常对照组(5.1±0.4 n/mm2比2.7±0.7 n/mm2,P＜0.01);而两组动脉组织中HIF-1α的mRNA表达及蛋白水平比较差异无统计学意义(P＞0.05).结论 高脂血症增加了兔主动脉管壁微血管密度及微血管内的血流量,但并不影响动脉管壁的氧供.

动脉粥样硬化(AS)是心脑血管疾病共性病理基础.本文从中医营卫交会生化角度探讨AS的形成机制,不仅丰富和发展了中医络病理论,而且有助于拓展研究思路,使我们的认识更加接近于事物本质,从而发挥中医中药在防治AS中的优势,为防治AS的发生、发展提供更多的干预靶点.

滋养血管(VV)在拉丁语中的意思是"血管的血管",是由一些微小血管构成的网状结构,包绕在大中血管壁的中外层,为宿主血管管壁提供氧气和营养物质并排出代谢废物.早在100多年前就有学者发现VV与动脉粥样硬化(AS)之间存在着密切关系,但随着AS研究热点的不断更换,VV的研究未能全面开展.近年来随着血管外膜结构与功能的深入研究以及显微CT和超声血管造影成像等技术在科研领域的应用,人们对VV的认识也越来越多,现就其在AS形成过程中的作用作一综述.

Objective:To investigate the intervention effect of Tongxinluo on the nailfold microcirculation blood flow velocity of hyperlipemia rabbits. Method:A total of 32New Zealand rabbits were randomly divided into control group,model group,atorvastatin group(2.5mg/Kg/d)and Tongxinluo group(0.3g/Kg/d),with 8in each group.Normal group was given ordinary feed,the rest of the groups were given a high-fat feed.The lipoprotein levels and the nailfold microcirculation blood flow velocity were observed at 2nd,4th and 6th week.Results:Compared with the control group,the lipid levels(TC,TG,HDL-C,LDL-C)of model group form the 2nd to the 6th week were significantly increased(P<0. 05).Atorvastatin group and Tongxinluo group lowered the TC level significantly in the 2nd week compared to the model group(P<0.05),andthe effect of the former was stronger(P<0.05).Atorvastatin group and Tongxinluo group TG level began to reduce significantly in the 2nd and 4th week respectively(P<0.05).The effect of increasing HDL-C level was not obvious in the two drug groups(P>0.05)except the atorvastatin group increased HDL-C level at 4th week(P<0.05),and both of them reduced the LDL-C levels in the 4th and 6th week(P<0.05).Compared with the control group,the nailfold microcirculation blood flow velocity in model group began to decline from the 2nd week(P<0.05).Compared with the model group,Atorvastatin group and Tongxinluo group can obviously improve microvascular blood flow velocity form the 2nd week(all P<0. 05),and the blood flow velocity of the latter was faster than the former in the 4th and 6th week(P<0.05).The experimental rabbit nailfold microcirculation blood flow velocity were negatively related with the four blood lipid levels(all P<0.05).Conclusion:Tongxinluo could significantly lower the levels of TC, TG and LDL-C,speed up the micro blood flow velocity,which provides the experimental basis for the clinical application of its improving microcirculation.

矽肺是在职业活动中长期吸入生产性粉尘并在肺内潴留而引起的以肺组织弥漫性纤维化为主的全身性疾病,随着肺组织纤维化的进展,肺功能逐渐下降,导致寿命和劳动年限显著缩短,给社会带来巨大损失,目前尚无根治办法[1].长期进展性的病痛折磨,严重影响矽肺患者的生存质量,为缓解和控制症状,改善其日常生活能力,提高生存质量,我们以Ⅱ期矽肺患者为研究对象,开展呼吸功能训练并配合汉防己甲素治疗,取得较为满意的临床疗效,报告如下.

Objective To observe the changes of nitric oxide(NO)and endothelin(ET)in acute carbon monoxide poisoning (ACOP)patients and investigate the protective action of Tongxinluo capsule on the vascular endothelial function.Methods The total of 90 ACOP patients were randomly divided into the treatment group and control group.By nitrate reduction and radio immunity method,two groups of patients respectively measured changes of NO and ET before and after treatment,and compared with 20 of healthy volunteers(normal group).Observed the treatment effect and the incidence of the delayed encephalopathy in the two groups.Results Compared with the healthy group,the content of NO was lower obviously(P<0.01)in treatment group,ET significantly increased in ACOP patients(P<0.01);NO and ET had significant differences after treatment both in control group and in treatment group(P<0.05,P<0.01).Moreover,compared with the control group,NO increased and ET reduced in Tongxinluo group(P<0.05).Conclusion Tongxinluo can protect the damaged vascular endothelial function of the ACOP patients by promoting NO secretion,inhibiting the generation of ET.

Objective To observe the protective effects ot Jiweiling lyophilized powder(JWLF) on the neuron of spinal cord injury(SCI) rats,and the influence on primary neuron apoptosis induced by glutamate in vitro,also explore the molecular mechanism of JWLF on the motor neuron disease(MND).Methods The SCI model of rats were developed with static compressive pressure of 30 g on the spinal epidural for 10 min,the neuron function was evaluated at 1 d,7 d and 14 d after the surgery and the morphologic changes of the damaged spinal were determined.The primary cortical neuron was damaged by glutamate at low concentration,then measure the viability and the expression of Bcl-2,Bax with methods of MTT,flow cytometry and Western blot.Results(1) JWLF could obviously improve BBB rating score on SCI rats at different time and release the edema of spinal neurons.(2) JWLF could enhance neuron activity in rat which suffered from glutamate and alleviate neuronal injury.(3) JWLF remarkably inhibited the neuron apoptosis induced by glutamate.(4) JWLF could balance the expression of Bcl-2 and Bax of neuron.Conclusion JWLF could promote hind limb motor function of SCI rats through enhancing the neuron activity and restraining the neuron apoptosis.

OBJECTIVE:To determine the anti-inflammatory functions of different cysteine mutants of apolipoprotein A-I recombinant HDLs.METHODS:The recombinant HDLs (named rHDL52, rHDL107, rHDL173, rHDLwt) were reconstituted by mixing wild types or their mutants with dipalmitoyl phosphatidylcholine. And the in vivo effects on lipopolysaccharide (LPS)-induced endotoxemia were examined in mice. The plasma levels of plasma tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6 in by ELISA were tested. And we also set up two control groups: LPS and saline.RESULTS:The rHDL52 mice had a significant decrease of plasma TNF-alpha and IL-1beta and the protection of lung against acute injury. 24 h post-injection as compared with rHDLwt group [TNF-alpha: (135.28 +/- 12.84) pg/ml, IL-1beta: (82.00 +/- 8.19) pg/ml], the rHDL52 mice exhibited a higher capability of lowering the plasma levels of TNF-alpha and IL-1beta [(39.66 +/- 2.44) pg/ml, (66.83 +/- 6.24) pg/ml, both P < 0.05]. And, as indicated by histological sections of lung tissue, the rHDL52 mice could also lower the infiltration of inflammatory cells in lung.CONCLUSION:rHDL52 has a higher anti-inflammation capability than wild type rHDLwt.

目的 观察络气郁滞证大鼠主动脉组织葡萄糖调节蛋白78(GRP78)mRNA表达的变化.方法 20只Wistar大鼠按体重随机分为正常组、络气郁滞组,实验末检测血清同型半胱氨酸(Hcy)、一氧化氮(NO)、血浆内皮素(ET),观察主动脉组织超微结构,以RT-PCR方法检测主动脉组织中GRP78mRNA的表达.结果 与正常组比较,络气郁滞组血清Hcy明显增高.NO明显下降(P<0.05),ET明显升高(P<0.05);主动脉组织超微结构发生明显改变,主动脉组织中GRP78mRNA的表达较正常组比较明显增强(P<0.01).结论 络气郁滞证大鼠的主动脉组织GRP78mRNA表达增强,其血管内皮功能障碍可能与主动脉组织内质网的应激有关.

Objective To establish and evaluate the rat animal model with collateral qi stasis.Methods To establish animal model with collateral qi stasis in 6 weeks by chronic constraint. To observe the changes of consciousness,appetite,body weight,the intake of cane sugar water,and the levels of CORT,ET,NO,5-HT.The ultramicrostructure change of aorta was observed by transmission electron microscope.Results The animal model rats showed deprementia,dull,no appetite,increasing slow of body weight,the cane sugar water intake was lowered significantly(P0.01 or P0.05),the levels of CORT,HCY,ET were increased significantly(P0.01 or P0.05),and the levels of 5-HT,NO were lowered significantly(P0.01 or P0.05).The ultramicrostructure of aorta changed obviously.Conclusion The animal model with collateral qi stasis is established with chronic constraint.The method has been succeed through observation the changes of body weight,cane sugar water intake,appetite,CORT,ET,NO,5-HT,and ultramicrostructure of aorta.The method is easy and the evaluated indexes are objective,which provide the good experiment foundation for the study of vessel-collateral and vascular system disorders.

目的 探讨通心络改善血管内皮功能的可能机制.方法 清洁级健康雄性Wistar大鼠随机分为4组(每组40只):①对照组;②高同型半胱氨酸(HCY)组;③络气虚滞(SCQDC)组;④通心络组.放免及化学方法检测内皮素(ET)、血栓素A2(TXA2)、前列环素I2(PGI2)、血浆肾素活性(PRA)、血管紧张素Ⅱ(AngⅡ)、醛固酮(ALD)、促肾上腺皮质激素释放激素(CRH)、促肾上腺皮质激素(ACTH)、糖皮质激素(GC)、白介素1β(IL-1β)、白介素2(IL-2)、白介素6(IL-6)水平及血清一氧化氮(NO)含量.ELISA方法检测去甲肾上腺素(NE)、白介素10(IL-10)水平.复杂系统分析方法分析血管内皮功能指标与神经内分泌-免疫网络(NEI net)之间的内在联系.结果 ①与对照组比较,SCQDC组ET-1、TXA2、Ang Ⅱ、CRH、IL-1β、IL-6水平显著升高,ACTH与GC水平明显下降.②与HCY组比较,PG12、NO含量、血浆肾素活性及GC水平显著降低,Ang Ⅱ及CRH显著升高,NE水平也呈现升高趋势.③与SCQDC组比较,通心络可显著降低ET-1、Ang Ⅱ、CRH、IL-1β、IL-6水平,同时明显升高ACTH、GC及NO水平,NE水平也有所降低.复杂系统分析结果显示,SCQDC组NEI网络相关指标与内皮功能指标之间分别构成了4个相互独立的系统,并存在递变规律,对照组、HCY组、通心络干预组则不存在这种子系统之间的相互联系.结论 络气虚滞型血管内皮功能障碍与NEI网络因子稳态失衡之间存在着密切相关性,后者可能是前者发生、发展的病理生理学基础之一,通心络改善络气虚滞条件下血管内皮功能的机制可能与其调节NEI网络的稳态有关.

目的:观察络气郁滞证候因素对血管内皮的作用并对机制进行探讨;方法:以慢性束缚法建立络气郁滞证候大鼠模型,观察大鼠的内皮结构、功能以及神经递质的变化.结果:模型大鼠血浆ET-1明显增高(P<0.05),血清NO明显下降(P<0.05),主动脉组织超微结构明显改变,血清皮质酮(CORT)、血浆血管紧张素Ⅱ(AngⅡ)、血清去甲肾上腺素(NE)、肾上腺素(E)明显增高(P<0.01或P<0.05).结论:络气郁滞证候引起血管内皮功能障碍、结构损伤,其机制可能与证候因素影响机体神经-内分泌网络紊乱有关.

AIM:To observe the effect of homocysteine (HCY) on the function of endothelium cell, and to discuss the possible mechanisms that Tongxinluo super powder affected.METHODS:Healthy male Wistar rats were divided into randomly the control group, the model group, the Tongxinluo group. The effect of Ach on isolated rat thoracic aorta in vitro was examined, the microcirculation was observed by microcirculation meter, the activity of SOD and GSH-PX and content of NO, MDA, ET, Ang II, TXA2, PGI2 was detected.RESULTS:Compared with control group, the effect of Ach on isolated rat thoracic aorta in vitro weakened markablely (P < 0.01), the format and percentage that capillary dilated declined significantly (P < 0.05), after treatment with Tongxinluo powder, the effect of Ach on isolated rat thoracic aorta in vitro was improved obviously (p < 0.01), and the format and percentage that capillary dilated were increased compared with model group; comparing with the control group, the level of Ang II and ET, TXA2 in plasm increased obviously (P < 0.05, P < 0.01), while the content of PGI2 depressed manifestly (P < 0.05), at the same time, both content of NO and activity of SOD, (GSH-PX declined obviously (P < 0.001, P < 0.05). After treatment with Tongxinluo powder, the level of ET, AngII and TXA2 reduced significantly in different degree (P < 0.01), while the content of PGI2 appeared stepping up notably (P < 0.01), and both activity of SOD and NO level increased obviously (P < 0.01, P < 0.05).CONCLUSION:(1) The high homocystein might cause the contracted and dilated function decreased, it might get involved in endothelium disfunction as a result of the massive free radicals production and diastolic-contract factors balance disorder induced by high homocystein. (2) Tongxinluo powder could improve the function of endothelium-dependment dilation induced by high homocystein, that associated with inhibitting the excessive production of free radicals, and improved function of endothelium.

1 材料与方法 1.1 材料 1.1.1 实验动物及分组健康Wistar雄性大鼠50只,体重200g～230g,购于北京维通利华实验动物中心,大鼠5只/笼,饲养在河北以岭医药研究院药理实验室,将大鼠按体重随机分为下列5组:(1)空白对照组:正常饲料饮食;(2)络气郁滞组:正常饲料饮食;(3)病理基础模型(HCY)组:3%蛋氨酸饮食(不限食);(4)病证复合模型组:3%蛋氨酸饮食(不限食).

Objectives: to establish the animal model of combining the syndrome of endothelial dysfunction and stagnancy of collateral-Qi in a deficiency condition(SCQDC).At the same time,the intervening mechanism of different kinds of herbs to dredge collateral was observed.Methods: healthy male Wistar rats of cleanness level were randomly devided into control group,the HCY group,the SCQDC group,the Renshen group,the Shuangshen group,the Tongxinluo group.The general condition of rats was observed each day.Tested the level of angiotensin Ⅱ(Ang Ⅱ),endothelin(ET),thromboxane A2(TXA2),prostacyclin I2(PGI2),nitrogen monoxidum(NO).Histochemical stain method was used to analyze the angiotensin converting enzyme in aorta thoracica tissue(ACE)and the expression of endothelium-typed nitrogen oxide synthase(eNOS),No.1 receptor of angiotensinⅡ(AT1),endothelin receptor(ET-1).The endothelial dependent diastolic percentages of blood vascularring in vitro was detected.Results: ①compared with control group and HCY group,and all the rats in SCQDC group appeared the following symptoms: obvious hypodynamia,insensitive response,skin slacked,body weight decreased,fur on the back dimmed,nose and tail being erythroic and rarely lustrous,stool being soft and shaped.In addition,the endurance capacity was significantly less than that of the control group.The condition of the rats in all treatment groups was slighted improved.② compared with the control group,the content of Ang Ⅱ in plasma of rats in the HCY group was significantly increased(P0.01),while the content of NO was significantly decreased(P0.05).The Ang Ⅱ,ET and TXA2 level in the SCQDC group was significantly increased than the level in the control group(P0.001,P0.05,P0.001).While the contents of PGI2 and NO in the SCQDC group were significantly decreased than the contents in the control group(P0.01),the content of Ang Ⅱ in the SCQDC group was much more increased than that in the HCY group(P0.05).After giving the three kinds of herbs to dredge collateral,the Ang Ⅱ,ET level in plasma was significantly decreased when compared with the SCQDC group(P0.01,P0.05),the content of NO was significantly increased(P0.05).③the immunohistochemical stain analysis showed that the expression of ACE,AT1,ET-1 was enhanced,compared with the control group and the HCY group,the eNOS expressions of the SCQDC group was significantly weakened,but the expression of AT1,ET-1was obviously enhanced.Three different kinds of herbs to dredge collateral could weaken the expression of AT1,ET-1 and enhance the eNOS expression in different degree.④the diastolic reactivity(diastolic percentage) analysis of the artery of rats in each group showed that the endothelial dependent diastolic percentage of blood vascular ring of the HCY group and the SCQDC group in vitro was significantly decreased compared with that of the control group(P0.05,P0.001).Compared with the SCQDC group,the endothelial dependent diastolic percentages of blood vascular ring in vitro of the Renshen group,the Shuangshen group and the Tongxinluo group were all increased in different degree.Conclusion: the result indicated that the symptims observed from the model rats established by combining methionine diet,basic diet,and weight loading swimming(such as listlessness,insensitive response,loss of weight,etc.) conformed with the clinical patients with stagnancy of collateral-Qi in a deficiency condition,and the endothelial dysfunction was further exacerbated compared with the HCY group,after the intervention of different kinds of herbs to dredge collateral,the above symptoms could be improved in different degree,which proved that the endothelial dysfunction model with stagnancy of collateral-Qi in a deficiency condition was established successfully.