一氧化氮和内皮素-1在内毒素休克后家兔血流动力学变化中的作用

目的 了解一氧化氮(NO)和内皮素-1(ET-1)在内毒素休克后血流动力学变化中的作用。方法 将24只家兔随机分为3组,依次为脂多糖(LPS)对照组,氨基胍(AG,诱生型一氧化氮合酶特异性抑制剂,20 mg·kg^-1)+LPS组和PD-142893(ET-1受体非选择性拮抗剂,0.02 mg·kg^-1)+LPS组。测定LPS对照组给LPS前及给LPS后0.5,1,2,4,6 h各时刻的血流动力学指标及血浆NO和ET-1浓度,AG+LPS组和PD-142893+LPS组分别于LPS静注后1 h给予AG和PD-142893,测定给LPS前及给LPS后1,2,4,6 h各时刻的血流动力学指标。结果 家兔LPS(1 mg·kg^-1)静注后,平均动脉压(MAP)在静注LPS后0.5 h就迅速下降30.31%(P<0.05),达到休克水平,继而保持平缓的下降趋势,至给LPS后6 h时降幅达40.61%(P<0.05);左室最大收缩压(LVSP)、左室内压最大上升/下降速率(±dp/dt max)等指标先迅速下降然后一定的回升继而平稳下降,而左室舒张末压(LVEDP)无明显变化(P>0.05)。内毒素休克家兔血浆NO水平呈双峰变化,在给LPS后0.5 h和6 h分别升高72.50%和95.83%(P<0.05),ET-1水平在晚期明显升高,在给LPS后6 h升高68.74%(P<0.05)。AG或PD-142893静注后各血流动力学指标均有明显改善。结论 NO和ET-1的生成可能参与了内毒素休克后血流动力学的变化,通过抑制它们的作用后血流动力学有明显改善。     

一氧化氮和内皮素-1在内毒素休克后家兔血流动力学变化中的作用

目的了解一氧化氮（N0）和内皮素-1（ET-1）在内毒素休克后血流动力学变化中的作用。方法将24只家兔随机分为3组,依次为脂多糖（LPS）对照组,氨基胍（AG,诱生型一氧化氮合酶特异性抑制剂,20mg·kg^-1）＋LPS组和PD-142893（ET-1受体非选择性拮抗剂,0．02mg·kg^-1）＋LPS组。测定LPS对照组给LPS前及给LPS后0．5,1,2,4,6h各时刻的血流动力学指标及血浆NO和ET-1浓度．AG＋LPS组和PD-142893＋LPS组分别于LPS静注后1h给予AG和PD-142893,测定给LPS前及给LPS后1,2,4,6h各时刻的血流动力学指标。结果家兔LPS（1mg·kg^-1）静注后,平均动脉压（MAP）在静注LPS后0．5h就迅速下降30．31％（P〈0．05）,达到休克水平,继而保持平缓的下降趋势,至给LPS后6h时降幅达40．61％（P〈0．05）;左室最大收缩压（LVSP）、左室内压最大上升／下降速率（±dp／dtmax）等指标先迅速下降然后一定的回升继而平稳下降,而左室舒张末压（LVEDP）无明显变化（P〉0．05）。内毒素休克家兔血浆NO水平呈双峰变化,在给LPS后0．5h和6h分别升高72．50％和95．83％（P〈0．05）,ET—1水平在晚期明显升高,在给LPS后6h升高68．74％（P〈0．05）。AG或PD．142893静注后各血流动力学指标均有明显改善。结论NO和ET-1的生成可能参与了内毒素休克后血流动力学的变化,通过抑制它们的作用后血流动力学有明显改善。     

支气管肺炎患儿血浆NO和ET含量改变的初步研究

目的：探讨一氧化氮（NO）和内皮素（ET）在支气管肺炎发病中的变化和意义。方法：应用生化Griess反应测定法、放射免疫法、分别测定30例普通肺炎患儿急性期和恢复期的血浆NO及ET水平,并与30例正常健康儿童作对照,用PCR法和血清检查测定肺炎患儿呼吸道病毒及细菌种类。结果：急性期肺炎患儿的血浆NO和ET水平较正常对照组、肺炎恢复期患儿明显升高（P＜0．01）,而不同病原感染时,血浆NO和ET水平无显著差异（P＞0．05）。结论NO和ET参与了肺炎的发生、发展过程,在不同病原引起的肺炎中,有着相似的病理生理变化,动态检测NO和ET的变化有着重要的意义。     

四逆汤对失血性休克家兔血浆内皮素（ET）的影响

目的:探讨中药四逆汤对失血性休克家兔内皮素的影响。方法:采用动物分组对照实验,测量不同状态下动物血浆内皮素(ET)的变化。结果:与休克前比较,休克组的家兔血浆ET水平各时段均明显提高(P<0.01),而治疗组仅在治疗后30min家兔血浆ET水平均明显提高(P<0.01),其他时段与休克前比较未见显著差异(P>0.05)。且休克后1h、4h、8h休克组ET水平显著高于治疗组(P<0.01)。经药物治疗的失血性休克家兔血浆ET水平明显降低。     

狼疮肾炎组织及血浆NO、ET-1检测的临床意义

目的　研究狼疮肾炎 (LN)病人组织及血浆内皮素 1(ET 1)和一氧化氮 (NO)检测的临床意义。方法　用放免法、ABC染色法及比色法分别对 4 0例LN病人分组测定ET 1和NO含量变化。结果　LN病人肾组织ET 1和NO的表达及血浆ET 1和NO含量均高于对照组 ,治疗后低于治疗前 (P <0 0 5～ 0 0 1) ,并随时间呈下降趋势 ;肾受损程度越重 ,血浆ET 1和NO含量越高 ;肾组织ET 1表达与血浆含量间呈正相关 (r =0 6 1～ 0 6 3,P均 <0 0 5 )。结论　LN病人测定组织及血浆NO、ET 1的含量可能对临床诊断和病情判断有帮助。     

老年性肺炎患者血浆NO、转化生长因子-β1、ET水平联合检测的临床意义

目的　探讨老年性肺炎患者血浆 NO、转化生长因子 -β1 和 ET含量的变化。方法　分别应用酶法和放射免疫分析法测定了 36例老年性肺炎患者血浆 NO、转化生长因子 -β1 和 ET水平 ,并与 30名正常健康人作对照。结果　老年性肺炎患者血浆中 NO、ET、转化生长因子水平高于正常人 (P<0 .0 5～ 0 .0 1 )。结论　老年肺炎患者血浆中NO、转化生长因子 -β1 、ET水平与疾病的发生和发展有密切的关系 ,其水平测定具有重要的临床价值     

单纯性肾病综合征患儿血中NO与ET的测定

目的:了解小儿肾病综合征发病过程中血浆中NO,ET浓度的变化特点。方法:采用分光光度法及放射免疫分析法检测了27例单纯性肾病综合征患儿及20例健康对照儿童血浆中NO,ET浓度。结果:血浆NO,NOS,ET在肾病患儿,正常对照组分别为(44.90±9.74μmol/L,13.84±3.44 U/mL,194.41±46.42 pg/ml);(80.46±13.43μmol/L,32.20±3.80U/mL,79.02±13.37pg/ml)。肾病患儿NO,NOS值显著降低(P<0.01),ET值显著增高。NO与NOS呈正相关(r=0.8798),NO与ET呈负相关(r=-0.6965)。结论:血浆NO,ET的浓度变化在肾病综合征患儿的病理生理过程中起着一定作用。     

限制性液体对创伤失血性休克患者的抢救效果及对血清NO、ET及cTnI的影响

目的 观察限制性液体对创伤失血性休克患者的抢救效果及对血清一氧化氮(NO)、内皮素(ET)、心肌肌钙蛋白I(cTnI)的影响.方法 60例创伤失血性休克患者,根据随机数字法分为观察组和对照组各30例.观察组为限制性液体复苏,对照组为非限制性液体复苏.比较两组患者治疗前和治疗后血清一氧化氮(NO)、内皮素(ET)、心肌肌钙蛋白I(cTnI)水平、液体输液量、复苏前后凝血酶原时间(PT)、部分凝血酶原时间(APTT)、急性呼吸窘迫综合征、多器官功能障碍综合征、尿毒血症发生率、病死率.结果 观察组的NO、ET及cTnI水平显著低于对照组.复苏后,观察组的输入液体量、PT、APTT值显著低于对照组(P<0.05).观察组的急性呼吸窘迫综合征、多器官功能障碍综合征、尿毒血症发生率、病死率显著低于对照组(P<0.05).结论 创伤失血性休克患者采取限制性液体复苏能有效调动患者机体凝血机制以及其他代偿机制,有利于重要脏器血流灌注的维持,有效降低血清NO、ET、及cTnT水平,提高治愈率.     

消瘀片对粥样硬化兔血管壁组织中ET、NO及细胞凋亡的影响

目的 :探讨消瘀片减少粥样硬化血管壁中平滑肌细胞数的作用机理。方法 :雄性新西兰兔高脂饮食加腹主动脉内膜剥脱术制成腹主动脉粥样硬化模型 ,通过放免法、比色法、原位末端标记及图像分析技术分别测定连续给予消瘀片 0 .1 6～ 0 .32g/(kg·d)治疗 1 6周后血管壁组织中ET、NO及细胞凋亡的变化。结果 :服用消瘀片后的兔粥样硬化血管壁组织中ET含量降低 ,NO含量增加 ,凋亡细胞阳性反应颗粒所占的面积和积分光密度值减少。结论 :消瘀片通过降低血管壁中的ET而抑制平滑肌细胞的增生 ,通过增加血管壁中的NO诱导细胞凋亡及加强对凋亡细胞的清除     

烟酰胺单核苷酸对内毒素休克小鼠死亡率的影响

目的 探究烟酰胺单核苷酸(NMN)对脂多糖(LPS)诱导的内毒素休克小鼠死亡率的影响.方法 将10周龄C57BL/6J雄性小鼠随机分组,均腹腔注射LPS(10 mg/kg)造模.NMN腹腔注射给药,分为3种方式:①造模后0.5 h给药,剂量为10、30、100、300 mg/kg;②造模前0.5 h给药,剂量为30、1...     

促甲状腺激素释放激素对大鼠内毒素性休克的影响

研究了不同剂量TRH(促甲状腺激素释放激素)对大鼠大肠杆菌内毒素性休克的影响,并与纳洛酮进行比较.发现低(0.22mg·kg~(-1),iv)、中(0.67mg·kg~(-1),iv)、高(2mg·kg~(-1),iv)剂量的TRH均能迅速纠正内毒素性低血压,且明显提高大鼠24h存活率.2mg·kg~(-1)纳洛酮的升压效应与低剂量TRH相当,但前者在较低血压水平上提高大鼠存活率的作用更强,此点与TRH不同.     

乙酰半胱氨酸对内毒素性休克兔的保护作用

研究乙酰半胱氨酸对内毒素体克兔的治疗作用。方法以大肠杆菌内毒素复制内纱休克模型,并分为对照组和ＮＡＣ治疗组,对两组间的血压变化,乳酸,丙二醛及一氧化氮的浓度变化进行了比较。     

Novel agents in the therapy of endotoxic shock

Endotoxic shock, or Gram-negative septic shock, can occur as a component of Gram-negative sepsis and is characterised by hypotension, poor tissue perfusion and multi-organ dysfunction. Despite antibiotic therapy and intensive care management, the morbidity and mortality rates of Gram-negative septic shock remain high. Endotoxin mediates its effects through interaction with receptors on the surface of a variety of host cells. These interactions result in the production and release of numerous biochemical mediators including nitric oxide, cytokines, prostaglandins and leukotrienes and toxic oxygen radicals. It is these biochemical mediators that exert toxic effects during endotoxic shock and which are often the target of novel treatment strategies. Several of these pharmacological agents are currently being investigated for use in Gram-negative septic shock and include inhibitors of the enzyme responsible for nitric oxide production, scavengers of the nitric oxide molecule and cytokine modulators. Although many agents have been studied for potential use as modulators of cytokine levels, this study will focus on pentoxifylline and the 21-aminosteroids, or lazaroids. Examination of the literature regarding pharmacological agents used to treat endotoxic shock often yields confusing and contradictory results. The reasons for these mixed results include differences in models, drug dosages, dosing methods and intervals and timing of administration relative to disease duration and severity. However, despite mixed results, several of the drugs discussed in this paper offer promise in the therapy of an often frustrating and lethal condition.     

苦参素对内毒素性休克致大鼠肾功能损伤的保护作用研究

目的观察苦参素对内毒素性休克大鼠肾损伤的保护作用。方法将24只雄性Wistar大鼠随机分为正常组(8只)、内毒素性休克组(8只)和苦参素治疗组(8只),内毒素性休克组和苦参素治疗组从股静脉注射脂多糖(LPS,15 mg/kg)建立内毒素性休克模型,造模15 min后,苦参素治疗组自股静脉输注苦参素注射液,观察其对平均动脉压(MAP)影响,实验结束后取材测定血浆中反映肾功能指标的尿素(Urea)、肌酐(Cr)含量,及肾组织匀浆中炎症因子白介素(IL)-6、IL-10、肿瘤坏死因子-α(TNF-α)的含量。结果苦参素治疗可防止内毒素性休克大鼠MAP的进行性下降;内毒素性休克组大鼠血浆Urea、Cr含量显著高于正常组,肾组织内IL-6、IL-10和TNF-α明显上升,苦参素治疗组大鼠血浆Urea、Cr含量显著低于内毒素性休克组,肾组织内IL-6和TNF-α显著下降。结论苦参素可对内毒素性休克后的肾功能提供一定的保护作用,其机制可能与抑制肾内促炎性细胞因子释放有关。     

抗内毒素多肽对内毒素休克模型家兔的治疗作用

目的:研究杀菌性/通透性增加蛋白模拟肽(BNEP)对内毒素休克家兔重要器官功能的影响。方法:家兔在静脉注射内毒素(LPS)500μg·kg-1后,立即注射BNEP5mg·kg-1,测定、分析不同时相点平均动脉压(MABP)、脉压差、血浆LPS、谷丙转氨酶(ALT)、肌酐(Cr)、肌酸磷酸激酶同工酶(CK-MB)的变化,观察8h死亡率。结果:BNEP组MABP下降速率减慢,并均在攻毒6h后恢复到攻毒前的80%以上。而LPS对照组平均动脉压、脉压差在攻毒后维持在低水平。BNEP组攻毒后各时相点血浆LPS浓度均显著低于单纯攻毒组,脉压差在2、4、6h时相点、CK-MB在4、6h时相点、Cr在6h时相点显著低于LPS组,且8h死亡率显著低于单纯攻毒组。但两组间ALT差别不显著。结论:BNEP具有较强的中和LPS能力,对内毒素休克家兔心血管系统、肾功能改善和恢复具有一定的效果。作为严重感染的辅助治疗手段可能具备较好的应用前景。     

38例地塞米松注射液致过敏性休克文献分析

目的探讨地塞米松注射液致过敏性休克的临床特点及规律，为临床合理用药提供参考。方法通过检索《中国期刊全文数据库》（1979和2006年）和《药物不良反应多媒体光盘》（1960—1997年）中关于地塞米松注射液致过敏性休克的病例报告，同时手工检索相关文献，对检索到的病例报告进行统计分析。结果在30种医药期刊中共检索到38例地塞米松注射液,31起过敏性休克。18—60岁的青、中年人占30例（78．9％）。经积极抗休克治疗后36例恢复正常，2亡（5．3％）。结论地塞米松引起过敏性休占并不少见，应引起临床高度重视，加强监测。保证用药安全。     

Propofol ameliorates liver dysfunction and inhibits aortic superoxide level in conscious rats with endotoxic shock

Propofol, widely used as a sedative agent, is known to exert antioxidant and anti-inflammatory effects in vitro. We studied the effects of propofol on hemodynamics and the function of several organs in conscious rats with endotoxemia. Intravenous injection of rats with endotoxin (lipopolysaccharide) caused hypotension, vascular hyporeactivity and tachycardia as well as significant lung, liver and kidney damage. Hepatocellular damage caused by lipopolysaccharide for 6 h was significantly attenuated in the lipopolysaccharide+propofol group. Aortic superoxide anion (O(2)(radical)(-)) production, but not plasma nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha) level, was also suppressed by propofol in lipopolysaccharide-injected rats. Light microscopy showed that propofol attenuated the marked infiltration of neutrophils in liver tissues from lipopolysaccharide-injected rats. Moreover, the survival rate of the lipopolysaccharide+propofol group at 16 h was significantly increased when compared with that of the lipopolysaccharide group (53% vs. 12%). These results suggest that inhibition of aortic O(2)(radical)(-) production and amelioration of liver dysfunction contribute to the beneficial effect of propofol in conscious rats with endotoxic shock.     

Effect of L-lysine on nitric oxide overproduction in endotoxic shock

1. An enhanced production of nitric oxide (NO) from L-arginine, related to the diffuse expression of an inducible NO synthase (iNOS), contributes to the pathogenesis of endotoxic shock. Since iNOS activity depends on extracellular L-arginine, we hypothesized that limiting cellular L-arginine uptake would reduce NO production in endotoxic shock. We investigated the effects of L-lysine, an inhibitor of L-arginine uptake through system y⁺, on NO production, multiple organ dysfunction and lactate levels, in normal and endotoxaemic rats.
2. Anaesthetized rats challenged with intravenous lipopolysaccharide (LPS, 10 mg kg⁻¹) received a 5 h infusion of either L-lysine (500 μmol kg⁻¹ h⁻¹, n=12) or isotonic saline (2 ml kg⁻¹ h⁻¹, n=11). In rats treated with saline, LPS produced a large increase in plasma nitrate and L-citrulline concentrations at 5 h, both markers of enhanced NO production. LPS also caused severe hypotension, low cardiac output and marked hyperlactataemia. All these changes were significantly reduced byL-lysine administration.
3. Endotoxaemia also caused a significant rise in the plasma levels of alanine aminotransferase (ALAT), lipase, urea and creatinine, and hence, liver, pancreatic and renal dysfunction. These changes tended to be less pronounced in rats treated with L-lysine, although the differences did not reach statistical significance.
4. Similar experiments were conducted in 10 rats challenged with LPS vehicle in place of LPS and then treated with L-lysine (500 μmol kg⁻¹  h⁻¹, n=5) or saline (2 ml kg⁻¹  h⁻¹, n=5) for 5 h. In these animals, all the haemodynamic and metabolic variables remained stable and not statistically different between both treatment groups, except for a slight rise in ALAT, which was comparable in L-lysine and saline-treated rats.
5. In conclusion, L-lysine, an inhibitor of cellular L-arginine uptake, reduces NO production and exerts beneficial haemodynamic effects in endotoxaemic rats. L-lysine also reduces hyperlactataemia and tends to blunt the development of organ injury in these animals. Contrastingly, L-lysine has no effects in the absence of endotoxin and thus appears to act as a selective modulator of iNOS activity.