牛蒡根水提物对高血压大鼠血管内皮损伤的保护作用

目的探讨牛蒡根水提物对高血压大鼠血管内皮损伤的保护作用及机制。方法用N-硝基-L-精氨酸(L-NNA)复制高血压大鼠模型,随机分为正常对照组、模型对照组、阳性对照组(卡托普利15 mg/kg)、牛蒡根水提物低剂量组(0.5 g/kg)、牛蒡根水提物中剂量组(1.0 g/kg)及牛蒡根水提物高剂量组(2.0 g/kg),连续灌胃6周,测定大鼠用药后1、4、7、10、13、16、19、22、29、36、42 d的收缩压;6周后,检测大鼠血清C-反应蛋白(CRP)、白介素-6(IL-6)水平,取大鼠胸主动脉,测细胞间黏附分子-1(ICAM-1)水平。结果 (1)牛蒡根水提物组的大鼠尾动脉收缩压低于模型对照组(P<0.05)。(2)牛蒡根水提物可显著改善血管的内皮损伤程度,抑制内膜内皮细胞脱落及血细胞黏附,并抑制中膜平滑肌细胞、胶原纤维增殖等。(3)牛蒡根水提物组的血清IL-6、CRP炎症因子及血管内皮ICAM-1表达水平低于模型对照组(P<0.05)。结论牛蒡根水提物对高血压大鼠血管内皮损伤具有明显改善作用,其机制可能与其抑制炎症因子IL-6、CRP及ICAM-1的表达,改善高血压大鼠血管内皮慢性炎症反应有关。     

六味地黄方对高脂血症大鼠血浆 ET、TXA2、PGI2水平及动脉内皮保护的影响

目的：研究六味地黄方对高脂血症大鼠血浆ET、TXA2、PGI2水平及动脉血管内皮保护的影响。方法：通过高脂饮食建立高脂血症大鼠模型,观察大鼠外周循环内皮细胞（CEC）、主动脉病理学、内皮素（ET）、前列腺素I2（PGI2）、血栓素A2（TXA2）的变化。结果：六味地黄方能减少高脂血症大鼠外周CEC及主动脉内皮细胞损伤;降低高脂大鼠血清ET、血浆TXA2,升高血浆PGI2水平。结论：六味地黄方对高脂血症大鼠内皮细胞具有保护作用,其作用机制可能与改善内皮细胞分泌功能有关。     

高原肺水肿患者血浆ET和SOD测定及其意义

目的 :探讨高原肺水肿 (HAPE)患者血浆ET和SOD的水平及在发病中的作用 ,方法 :采用放射免疫法测定血浆ET、SOD、AⅡ 的含量 ,用Griss反应法检测NO水平。结果 :HAPE患者血浆NO和SOD水平显著低于高原健康组 (P <0 0 1 ) ,ET和AⅡ 水平显著高于高原健康组 (P <0 0 1 ) ,结论 :血管活性物质平衡失调及血管内皮细胞损伤是HAPE发病的重要原因之一。     

芪丹合剂对高脂血症大鼠血浆ET和CGRP的影响

目的研究芪丹合剂对高脂血症大鼠血浆的作用。方法采用喂食高脂饲料方法复制大鼠高脂血症模型,以复方丹参片为对照,检测各组大鼠血浆的内皮素(ET)和降钙素基因相关肽(CG RP)含量。结果用药各组在50d后,上述两指标与模型组相比均有不同程度改善,高剂量组最为明显(P<0.01)。用药80d后,上述差异更加显著。结论芪丹合剂可以降低高脂血症大鼠血浆中ET含量,升高CGRP含量,具有血管内皮保护作用。     

法舒地尔对肺动脉高压大鼠肺血管内皮功能的影响

目的 观察法舒地尔对肺动脉高压(PH)大鼠肺血管内皮功能的影响.方法 成年大鼠32只分为正常对照3周组(C3),PH模型3、6周组(P3、P6)及法舒地尔治疗组(F6)各8只,F6组给予法舒地尔腹腔内注射治疗.实验后测定右心室收缩压(RVSP)及血浆内皮素 1(ET 1),观察肺小动脉内皮病理变化.结果 P3组较C3组的RVSP、ET 1明显升高,P6组较P3组继续升高,差异均有统计学意义(P<0.05);而F6组与P3组比较,差异无统计学意义(P>0.05),较P6组有降低但差异无统计学意义(P>0.05).F6组较P3、P6组内皮细胞相对完整,管腔狭窄则显著减轻.结论 法舒地尔能降低RVSP、ET 1水平,显著改善PH大鼠肺血管内皮功能,降低肺动脉压力.     

倒卵叶五加总皂苷对心肌缺血再灌注大鼠左心功能和血清一氧化氮及血浆内皮素的影响

目的　观察倒卵叶五加总皂苷对心肌缺血再灌注大鼠左心功能和血清一氧化氮 (NO)及血浆内皮素 (ET)的影响。方法　建立在体大鼠缺血再灌注损伤模型 ,用心功能分析系统测定左室心功能 ,用酶法测定血清NO水平及放免法测定血浆ET水平。实验分假手术组 (sham)、心肌缺血再灌注损伤组 (IR)和倒卵叶五加总皂苷 (SAOH ,10 0mg·Kg-1)治疗组。结果　IR组左室LVSP ,+dp/dtmax,-dp/dtmax,+dp/dtmax/IP明显下降 (P <0 .0 0 1) ,血清NO水平明显降低 ,而血浆ET水平则显著升高(P <0 .0 0 1) ;SAOH能够明显改善缺血再灌注损伤大鼠左心LVSP ,+dp/dtmax,-dp/dtmax,+dp/dtmax/IP ,提高血清NO ,降低血浆ET ,恢复NO/ET平衡 (P <0 .0 0 1)。结论　倒卵叶五加总皂苷能提高心肌缺血再灌注损伤大鼠血清NO水平和降低血浆ET含量 ,恢复NO/ET平衡 ,改善左心舒缩功能。     

银杏黄酮磷脂复合物对血管内皮保护作用初探

目的:探讨银杏黄酮磷脂复合物对大鼠缺血再灌注状态下血管内皮的保护作用。方法:健康Wister大鼠40只,随机分为假手术组、模型组、银杏黄酮组及银杏黄酮磷脂复合物组,每组10只,检测各组血浆内皮素(ET1)、血清一氧化氮(NO)水平,并取心尖部心肌做电镜,观察血管内皮的显微结构变化。结果:大鼠在心肌缺血30min再灌注120min状态下,银杏黄酮磷脂复合物可明显降低血清NO含量,亦使血浆ET1水平下降,同时改善血管内皮超微结构的破坏程度,且变化较银杏黄酮组显著。结论:银杏黄酮磷脂复合物对大鼠心肌再灌注血管内皮损伤具有保护作用,可能与其减少自由基对内皮细胞的氧化损伤,减少内源性血管活性物质ET1释放有关。     

老年慢性肺心病血浆内皮功能测定的临床意义

目的　观察老年慢性肺心病血浆内皮功能即血浆内皮素 1(ET 1)和血管性假血友因子 (vWF)测定的临床意义。方法　随机抽取老年慢性肺心病病人高危组和低危组各 30例 ,入院第 1d晨空腹采肘静脉血 ,分离血浆后 ,用放射免疫法和双抗夹心酶联免疫吸附法 ,进行ET 1和vWF的含量测定 ,并与体检健康老年组 30例做对照 ,进行统计学处理。结果　血浆ET 1和vWF含量测定值 ,低危组较对照组增高 ,P <0 0 5 ;高危组较低危组增高 ,P <0 0 5 ;老年慢性肺心病组 (高危组 +低危组 )较对照组显著增高 ,P <0 0 1;高危组较对照组显著增高 ,P <0 0 1。结论　老年慢性肺心病病情越重其ET 1和vWF值增高越明显 ,两者呈正相关 ,ET 1和vWF值越高 ,预后越差。血浆内皮功能测定可作为判断老年肺心病病人预后的指标之一。     

益气通络丹对冠心病病人血浆内皮素、一氧化氮及红细胞变形性的影响

目的 :本实验观察冠心病 (CAD)病人使用益气通络丹治疗前后血浆内皮素 (ET)、一氧化氮 (NO)水平及红细胞变形性 (ED)。方法 :检测 39例 CAD病人治疗前后血浆 ET、NO水平及 ED。结果 :冠心病病人血浆 ET水平升高 (P<0 .0 1)、NO水平降低 (P <0 .0 1) ,红细胞滤过指数 (IF)增高 (P <0 .0 1)。治疗后血浆 ET水平下降 (P <0 .0 1) ,NO水平明显升高(P<0 .0 1) ,红细胞 IF降低 (P <0 .0 1)。对照组治疗前后各项指标均无明显变化。结论 :益气通络丹可改善 CAD病人血管内皮细胞功能 ,改善 CAD病人血浆 ET和 NO水平 ,提高红细胞变形性 ,对 CAD心绞痛具有一定的治疗价值     

参芪培元口服液保护急性心肌缺血损伤的机制研究

目的:研究参芪培元口服液预处理对急性心肌缺血大鼠心血管的保护作用.方法:设假手术组、模型对照组、维拉帕米组、参芪培元口服液组,建立急性心肌缺血模型.造模后2 h时采血测血浆内皮素(ET)、降钙素基因相关肽(CGRP)、循环内皮细胞(CEC)计数,并进行心肌病理形态学观察.结果:参芪培元口服液和维拉帕米均可显著降低急性心肌缺血大鼠血浆ET和CEC水平,减轻心肌病理形态学改变.同时两组的血浆CGRP均显著低于模型对照组(P＜0.05).参芪培元口服液组和维拉帕米组间的上述3指标无显著性差异.结论:参芪培元口服液预处理可减轻心肌及血管内皮细胞损伤,调节急性心肌缺血时所发生的ET,CGRP分泌失衡.     

动态观察实验性高脂血症对血管内皮活性物质含量及其基因表达的影响以及DDPH的内皮细胞保护作用

目的　观察在高脂血症动物模型形成过程中不同程度的高血脂以及DDPH对动脉血中NO、ET 1含量以及动脉壁eNOS、内皮素 1基因表达的影响。方法　在实验性家兔高脂血症模型基础上 ,采用半定量逆转录多聚酶链式反应(RT PCR)等技术 ,观察了不同时期的高脂血症对内皮素及一氧化氮代谢的影响以及DDPH的干预作用。结果　不同时期的高脂饮食可造成不同程度的高脂血症 ,相应的血管内皮细胞的内皮素 1和一氧化氮的代谢紊乱也有所不同 :轻、中度高脂血症可引起eNOS及内皮素 1mRNA表达水平升高和外周血ET 1含量增高 ;而重度高脂血症可引起eNOS及内皮素mRNA表达水平下降和外周血NOP、ET 1浓度降低 ;DDPH(ig)可明显降低实验性家兔的高血脂 ,并同时促进一氧化氮代谢产物 (NOP)、ET 1含量的升高和eNOS、ET 1mRNA的表达。结论　不同程度的高脂血症对血管内皮活性物质及其基因表达的影响是不同的。DDPH可保护血管内皮细胞 ,恢复血管活性物质合成和释放 ,从而恢复血管的反应性     

内皮素-1在暴发性肝功能衰竭发生中的作用

目的　观察内皮素 (ET) - 1在暴发性肝功能衰竭发生中的作用。方法　以硫代乙酰胺 (TAA)灌胃染毒的方法建立大鼠暴发性肝功能衰竭模型 ,利用生化方法测定血浆内毒素及内皮素水平 ,采用 ET抗血清拮抗 ET- 1的作用。结果　 TAA组血浆内皮素、内毒素和血清丙氨酸转氨酶水平显著高于正常对照组 (P<0 .0 5 ) ;TAA +ET- Ab组血浆内皮素、内毒素和丙氨酸转氨酶水平显著低于 TA A组 (P<0 .0 5 ) ,内皮素与内毒素水平呈显著正相关 (P<0 .0 1) ,内皮素抗血清可以拮抗 ET- 1的作用并可减轻肝坏死的程度。结论　内皮素可上调血浆内毒素水平 ,与暴发性肝功能衰竭的发生密切相关     

Endothelin receptor-mediated vasodilatation: effects of organ culture

Culture of intact arteries is a frequently employed experimental model for investigating the mechanisms governing the regulation of vascular endothelin receptors. Endothelin type A (ET(A)) and type B (ET(B)) receptors on vascular smooth muscle cells are up-regulated in organ culture and the enhanced vasoconstriction mimics the changes that occur in cardiovascular disease. The effect of organ culture on endothelial dilatory endothelin ET(B) receptors is not known. We hypothesize that organ culture decreases the endothelin receptor-mediated dilatation and that this is one possible mechanism by which the effects of the endothelin in blood vessels are altered during culture. Porcine coronary arteries were studied before and after 24 h of culture, using in vitro pharmacology and immunofluorescence. Sarafotoxin 6c and endothelin-1 were used to examine the endothelin ET(A) and ET(B) receptor effects, and the antagonists, Nomega-nitro-l-arginine (l-NOARG) for nitric oxide (NO), indomethacin for prostaglandins and charybdotoxin in combination with apamin for endothelium-derived hyperpolarizing factor (EDHF), were used to study the endothelium-derived dilatory mediators. Organ culture induced up-regulation of the sarafotoxin 6c (ET(B) receptor agonist) and endothelin-1 (ET(A) receptor agonist) elicited vasoconstriction. The sarafotoxin 6c contraction was stronger after endothelium denudation, suggesting endothelium-dependent dilatation. The endothelin-1 contraction was not affected by endothelium denudation. The increase in sarafotoxin 6c contraction after removal of the endothelium was more pronounced before than after organ culture, suggesting down-regulated endothelial endothelin ET(B) receptors. Also, the immunofluorescence staining intensities for endothelial endothelin ET(B) receptors were higher before than after organ culture. Pre-incubation with inhibitors for dilatory mediators suggested that both NO and EDHF play a vasodilatory role, while prostaglandins are not involved. In conclusion, endothelial endothelin ET(B) receptors induce NO and EDHF mediated vasodilatation in porcine coronary arteries. In organ culture, endothelial endothelin ET(B) receptors are down-regulated, mimicking the changes that occur in cardiovascular disease. Down-regulation of endothelial endothelin ET(B) receptors may in part explain the increased endothelin ET(B) receptor-mediated vasoconstriction frequently studied in organ culture.     

Enhanced G-protein coupled receptors-mediated contraction and reduced endothelium-dependent relaxation in hypertension

The present study was designed to demonstrate a hypothesis that some G-protein coupled receptors are up-regulated and a dysfunction of endothelium occurs in hypertension. The arteries from hypertensive patients and spontaneously hypertensive rats (SHR) were tested. An in vitro myograph system was used to obtain concentration-contraction curves mediated by endothelin ET(A), endothelin ET(B), 5-hydroxytryptamine 2A (5-HT2A)-receptors and alpha1-adrenoceptors in the arterial segments. In hypertensive patients, the maximum contractions (Emax) induced by endothelin ET(B), endothelin ET(A) and 5-HT receptors were significantly increased with elevated pEC50 values, while a significantly leftward shift of alpha1-adrenoceptor-mediated contraction was seen. Similar results were obtained in SHR. Specific antagonists for 5-HT2A receptors or alpha1-adrenoceptors rightward shifted the concentration-contractile curves induced by 5-HT or noradrenaline, while the Emax were not significantly altered, suggesting that the contractions were mediated by 5-HT2A receptors and alpha1-adrenoceptors, respectively. Endothelium-dependent maximum relaxation (Rmax) in the arterial segments induced by acetylcholine was significantly decreased in both hypertensive patients and SHR. In addition, nitric oxide- and endothelium-derived hyperpolarizing factor-mediated dilatations were decreased significantly and the arterial endothelial cells were in part lost in SHR. In conclusion, endothelin ET(B), endothelin ET(A), 5-HT2A receptor- and alpha-adrenoceptor-mediated contractions were increased in hypertension, while the endothelium and its functions were damaged.     

Endothelin in the mechanism of endothelial injury and neutrophil adhesion in the post-ischemic guinea-pig heart.

This study addressed the hypothesis that endothelin promotes neutrophil accumulation in ischemic/reperfused myocardium, not only via its direct effect on neutrophils, but also because it mediates post-ischemic endothelial injury. Langendorff-perfused guinea-pig hearts were subjected to 30 min ischemia/35 min reperfusion, and infusion of neutrophils between 15 and 25 min of reperfusion. The infusion of the endothelin ET(A)/ET(B) receptor antagonist, tezosentan, the endothelin ET(A) receptor antagonist, BQ 123 [cyclo(-D-Trp-D-Asp-Pro-D-Val-Leu-], and superoxide dismutase was terminated at reperfusion, 5 min before the start of the neutrophil infusion, to avoid the contact of the drugs with neutrophils. Coronary flow responses to acetylcholine and nitroprusside were used as measures of endothelium-dependent and -independent vascular function, respectively. Neutrophil adhesion and endothelium glycocalyx ultrastructure were assessed in histological preparations. Ischemia/reperfusion resulted in a 54%-impaired acetylcholine response, endothelium glycocalyx disruption, and enhanced neutrophil adhesion (21.6% of microvessels contained neutrophils vs. 2.6% in sham group), the latter prevented by a selectin blocker, sulfatide, 20 microg/ml. These alterations were completely prevented by 0.5 and 5 nM, but not 0.05 nM, tezosentan, and were greatly attenuated by BQ 123, 1 and 10 nM. The glycocalyx-protective effect of these interventions preceded their effect on neutrophil adhesion. Superoxide dismutase, 150 IU/ml, reported before by us to protect post-ischemic endothelium glycocalyx, here prevented the post-ischemic endothelial dysfunction and neutrophil adhesion. The data imply that neutrophil adhesion in ischemic/reperfused guinea-pig heart is a selectin-dependent process, secondary to mostly endothelin ET(A) receptor- and free radical-mediated functional and/or structural changes in the coronary endothelium. Thus, endothelin ET(A)/ET(B) as well as ET(A) receptor antagonists may be useful in attenuation of the inflammatory response in ischemic/reperfused heart. The antagonists may be effective because of their direct effect on neutrophils, as demonstrated by others, and because they provide endothelial protection, as demonstrated here.     

七叶皂苷钠对大鼠弥散性脑损伤合并二次脑损伤的保护作用研究

目的:研究七叶皂苷钠对大鼠弥散性脑损伤合并二次脑损伤的保护作用。方法:实验分为4组,即对照、模型及七叶皂苷钠高、低剂量组,分别测定大鼠脑组织白介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)、内皮素(ET)和一氧化氮(NO)水平。结果:与对照组比较,模型组大鼠脑组织IL-1β、TNF-α、ET和NO水平显著升高(P<0.05);与模型组比较,七叶皂苷钠高剂量组大鼠脑组织IL-1β、TNF-α、ET和NO水平显著下降(P<0.05)。结论:七叶皂苷钠可通过抑制炎性因子、清除氧自由基和稳定血管内皮细胞等机制发挥保护神经组织的作用。     

支气管哮喘患儿血内皮素、一氧化氮含量测定的临床意义

目的　探讨了支气管哮喘患儿血内皮素和一氧化氮含量的变化。方法　应用放免法和化学法测定了 38例支气管哮喘患儿血内皮素和一氧化氮含量、并与 35名正常健康人作比较。结果　支气管哮喘患儿血内皮素水平明显升高 (P<0 .0 1)。一氧化氮水平明显下降 (P<0 .0 1)且与患儿病情程度有关。结论　支气管哮喘患儿血管内皮细胞存在内分泌功能的紊乱 ,ET合成释放增加 ,一氧化氮释放减少 ,以及两者反馈调控失衡在支气管哮喘的发病中具有重要意义     

Enhanced expression of contractile endothelin ET(B) receptors in rat coronary artery after organ culture

Endothelin-1 is a potent vasoconstrictor mediating its effects via two receptor subtypes, the endothelin type A (ET(A)) preferentially situated on smooth muscle cells, mediating vasoconstriction and endothelin type B (ET(B)) mainly located on endothelial cells, mediating vasodilatation. In cardiovascular disease and in organ culture in vitro, endothelin ET(B) receptors are up-regulated on smooth muscle cells. The objectives of the present study were to characterise the endothelin receptor-induced vasoconstriction and quantify the endothelin receptor mRNA levels and immunoreactivity in fresh and cultured rat coronary arteries. We demonstrate that endothelin-1 induces strong and equal concentration-dependent contractions in fresh and cultured segments from the left anterior descending coronary artery. Sarafotoxin 6c, an endothelin ET(B) receptor agonist, had negligible effect in fresh arteries but produced significant vasoconstriction after organ culture. The endothelin ET(B) receptor mRNA level and the receptor protein immunoreactivity were increased, whereas the level of endothelin ET(A) receptor mRNA was down-regulated but not its receptor protein immunoreactivity after organ culture. Pharmacological inhibition of endothelium-derived dilatory mediators did not influence endothelin ET(A) or ET(B) receptor-mediated vasoconstriction in fresh segments. In cultured arteries, inhibition of endothelial vasodilators potentiated the effect of sarafotoxin 6c. In conclusion, endothelin ET(B) receptor stimulation in cultured coronary arteries elicits vasoconstriction. This is likely not related to endothelial dysfunction with putative loss of its vasodilator components, but rather explained by the up-regulation of contractile endothelin ET(B) receptors on smooth muscle cells.     

Effect of atorvastatin on endothelium-dependent constrictor factors in dyslipidemic rabbits

Relaxations to acetylcholine and contractions to acetylcholine in the presence of the nitric oxide (NO) synthesis inhibitor (L-N(G)-nitroarginine methyl ester, L-NAME) were studied in aortic rings from rabbits fed either a control or a diet containing 0.5% cholesterol+14% coconut oil for 14 weeks and treated or not with atorvastatin (2.5 mg kg(-1) day(-1)). Rings were incubated with the endothelin (ET(A)) receptor antagonist BQ123, and/or the thromboxane A(2) (TXA(2))/prostaglandin H(2) (PGH(2)) receptor antagonist ifetroban. In rabbits, high cholesterol and triglyceride plasma levels were associated with intimal thickening and blunted acetylcholine-relaxation as compared with controls. By contrast, acetylcholine+L-NAME response was higher. Incubation with either ifetroban or BQ123 increased acetylcholine-relaxation in both diet groups and it reduced the constrictor response only in dyslipidemic rabbits. Removal of endothelium reduced acetylcholine+L-NAME contraction in dyslipidemic rabbits, although increased it in control animals. Atorvastatin treatment reduced plasma lipid levels and lesion size in dyslipidemic animals. Likewise, it prevented acetylcholine-relaxation reduction. In addition, atorvastatin reduced constrictor response in dyslipidemic rabbits but only in rings with endothelium. Incubation with either ifetroban or BQ123 did not further modify these responses in atorvastatin-treated animals in any group. These data suggest that ET and TXA(2) availabilities seem to participate in the endothelial dysfunction associated with dyslipidemia. Atorvastatin treatment reduces intimal thickening and improves endothelial dysfunction in rabbits. This effect seems to be a consequence of its ability to act on ET and TXA(2) systems.