葛根素对家兔肝缺血再灌注一氧化氮、内皮素-1的影响

目的观察一氧化氮(NO)、内皮素-1(ET-1)在家兔肝缺血再灌注损伤过程中的变化及葛根素(Pur)对其的影响。方法实验家兔随机分为3组:对照组(C组,n=10)、缺血再灌注组(IR组,n=10)和葛根素治疗组(Pur组,n=10)。分别测定缺血前,缺血第45分钟及再灌注第45分钟时肝组织NO,ET-1含量,用电镜观察家兔HIRI及经Pur保护后的肝组织形态学改变。结果家兔缺血再灌注第45分钟时,与C组、Pur组比较:IR组血浆及组织NO含量均明显较低(P<0.01,P<0.05);IR组血浆及组织ET-1含量明显较高(P<0.01,P<0.05);与IR组比较,Pur组肝组织超微结构明显改善。结论葛根素可通过调节机体NO和ET-1水平而对肝缺血再灌注损伤发挥积极的保护作用。     

Acute Mesenteric Ischemia: The Challenge of Gastroenterology

Intestinal ischemia has been classified into three major categories based on its clinical features, namely, acute mesenteric ischemia (AMI), chronic mesenteric ischemia (intestinal angina), and colonic ischemia (ischemic colitis). Acute mesenteric ischemia is not an isolated clinical entity, but a complex of diseases, including acute mesenteric arterial embolus and thrombus, mesenteric venous thrombus, and nonocclusive mesenteric ischemia (NOMI). These diseases have common clinical features caused by impaired blood perfusion to the intestine, bacterial translocation, and systemic inflammatory response syndrome. Reperfusion injury, which exacerbates the ischemic damage of the intestinal microcirculation, is another important feature of AMI. There is substantial evidence that the mortality associated with AMI varies according to its cause. Nonocclusive mesenteric ischemia is the most lethal form of AMI because of the poor understanding of its pathophysiology and its mild and nonspecific symptoms, which often delay its diagnosis. Mesenteric venous thrombosis is much less lethal than acute thromboembolism of the superior mesenteric artery and NOMI. We present an overview of the current understanding of AMI based on reported evidence. Although AMI is still lethal and in-hospital mortality rates have remained high over the last few decades, accumulated knowledge on this condition is expected to improve its prognosis.     

NOS、ET-1在血吸虫病门静脉高压兔肺组织中的表达和意义

目的　探讨内皮素 (endothelin -1,ET -1)、一氧化氮 (NO)在血吸虫病门静脉高压性肺血管病变发病机制中的作用。方法　运用腹部敷贴法感染血吸虫尾蚴形成血吸虫病肝硬化门静脉高压症动物模型 ,模型组 (M组 ) 10只和正常对照组 (N组 ) 10只 ,应用免疫组织化学法对动物模型的肺组织中的ET -1、一氧化氮合酶 (nitricoxidesynthase ,NOS)进行定位性研究 ,并以正常兔作对照。结果　感染血吸虫尾蚴 12 0d后 ,肝硬化门静脉高压症动物模型成功 ,模型组肺组织中ET -1、NOS阳性细胞的表达均明显增多 ,染色增强 ,计算机图像定量分析示两组光灰度值和光密度值均具有显著性差异 (P <0 .0 1)。结论　ET -1、NOS在血吸虫病门静脉高压兔肺血管中的表达明显增强 ,表明ET -1、NO在血吸虫病门脉高压性肺血管病变发病机制中具有重要意义。     

急性肠系膜血管供血不全的诊断和治疗

目的：探讨急性肠系膜血管供血不全的诊断和治疗方法。方法：回顾性分析30例急性肠系膜血管供血不全的临床资料。26例(86．7％)年龄大于60岁；17例(56．7％)合并有心血管疾病及其它疾病。27例行急诊手术治疗，其中23例行小肠部分切除吻合术，2例行肠系膜上动脉取栓术，2例因肠系膜上动脉广泛梗塞、小肠广泛坏死未作处理。结果：25例(83．3％)发生绞窄性肠梗阻。3例因病情危重，未经手术即死于感染性休克和心肺功能衰竭。余27例均经手术治疗，治愈14例(46．7％)，死亡13例，总病死率53．3％。结论：充分认识该病，选用恰当的检查技术早期诊断，及时手术，是提高急性肠系膜血管供血不全治疗效果的关键。     

In the Experimental Model of Acute Mesenteric Ischemia,The Correlation of Blood Diagnostic Parameters with the Duration of Ischemia and their Effects on Choice of Treatment

ABSTRACT

Purpose/Aim: Acute mesenteric ischemia is a syndrome characterized by sudden onset abdominal pain followed by intestinal necrosis. Morbidity and mortality increase with delayed diagnosis. Even with the latest radiological diagnostic methods, early diagnosis and initiation of treatment can be delayed. Using an experimental model, here we aim to determine the relationship between the laboratory parameters used to detect acute mesenteric ischemia and the duration of irreversible ischemia. Materials and Methods: A total of 30 male Wistar albino rats were divided into five groups, all of which underwent general anesthesia: (i) Superior mesenteric artery (SMA) dissection with laparotomy was performed, and blood samples and intestinal segment samples were taken after 2 hr (Sham group); (ii) volvulus of one-third of the small intestines was performed manually by laparotomy, and blood samples and intestinal segment samples were taken after 2 hr (Volvulus group); (iii) SMA was ligated with laparotomy, and blood samples and intestinal segment samples were taken after 2 hr (SMA+ligated 2-hr group); (iv) SMA was ligated with laparotomy, and blood samples and intestinal segment samples were taken after 4 hr (SMA+ligated 4-hr group); and (v) SMA was ligated with laparotomy, and blood samples and intestinal segment samples were taken after 6 hr (SMA+ligated 6-hr group). Results: The mean lactate dehydrogenase (LDH) activities of the SMA+ligated 2-hr and SMA+ligated 6-hr groups were statistically higher than the control group (p = .004). Compared to the Sham and Volvulus groups, the mean lactate level of the SMA+ligated 6-hr group was significantly higher (p = .004). Compared to the Sham and Volvulus groups, the mean D-dimer levels of the SMA+ligated 4-hr and SMA+ligated 6-hr groups were significantly higher (p = .004 and .003, respectively). By histopathological evaluation, we found that pathological damage increased as the ischemia lengthened. Conclusions: Mesenteric ischemia leads to an irreversible loss of intestinal perfusion and an increase in parameters of ischemia. Irreversible tissue damage occurs after 4 hr of ischemia and peaks after 6 hr, whereas parameters of ischemia (D-dimer, LDH, and L-Lactate levels) are highest at 2 hr after the onset of ischemia.     

Significance of Antithrombin III,Protein C and Protein S in Acute Mesenteric Ischemia Patients

It is well established that a condition of hypercoagulation due to deficiencies of antithrombin III, protein C and protein S may result in thrombo-embolism. To evaluate the possibility of hypercoagulation in acute mesenteric ischemia (AMI); clinical features, ECG changes, drug history, the length of intestine remaining after the resection and mortality of 15 consecutive patients were recorded and plasma levels of antithrombin III, Protein C and protein S were measured. Antihypertensive, antidiabetic and digitalis were the main drugs used by the patients. Atrial fibrillation was the main ECG finding (60%). AMI was attributed to thrombo-embolic phenomena because of atrial fibrillation in these patients. Levels of antithrombin III and protein S were lower in patients without atrial fibrillation compared to those with the condition (mean values 16.18 vs. 18.04 and 87.33 vs. 94.22 respectively) but the difference was not statistically significant. Levels of Protein C were lower and the length of intestine remaining after resection was shorter in patients without, compared to those with, atrial fibrillation (mean values 77.00 vs. 88.66, and 52.5 cm vs. 86.11 cm respectively). The difference was statistically significant (p < 0.05). Postoperative mortality rate was 33.3% (5 patients) and the length of intestine remaining after resection was the main determining factor in the prognosis of the patients. We conclude that a condition of hypercoagulation due to a deficiency of protein C has a significant role in the pathogenesis of AMI especially in patients without atrial fibrillation.     

急性肠系膜血管缺血性疾病16例诊治体会

目的探讨急性肠系膜血管缺血性疾病(acute mesenteric ischemia,AMI)的诊断和治疗方法。方法回顾性分析16例AMI患者的临床资料。16例急诊行64排128层螺旋CT扫描及三维重建,诊断为肠系膜上动脉栓塞6例、肠系膜下动脉栓塞1例、肠系膜上静脉血栓形成7例(同时伴有门静脉血栓形成2例),阳性率87.5%,阴性结果2例,再行选择性肠系膜上动脉造影,诊断为肠系膜上动脉血栓形成。4例接受以溶栓为主的非手术治疗,12例行急诊手术。结果非手术治疗的4例症状、体征均消失,肠管功能恢复正常,痊愈出院。12例手术患者中11例痊愈出院,1例死亡,死亡原因为MODS。结论AMI早期诊断意义重大,128层加强螺旋CT肠系膜血管成像有助于AMI的早期诊断,早期溶栓和及时手术切除坏死肠管,对挽救患者的生命有重要意义。     

Posttreatment with Aminoguanidine Attenuates Renal Ischemia/Reperfusion Injury in Rats

Acute renal failure secondary to ischemia/reperfusion (I/R) injury is associated with significant mortality and morbidity. Aminoguanidine (AG), an inducible nitric oxide synthase inhibitor with antioxidant properties, has been reported beneficial in renal I/R injury. The aim of the present study was to investigate the effect of AG on renal I/R injury and compare the effectiveness of different AG treatment modalities. Sprague-Dawley rats were randomly assigned to one of four groups. The control group (n?=?6) received sham operation. The I/R group (n?=?6), AG-I group (n?=?8), and AG-II group (n?=?8) received bilateral renal ischemia for 45 min followed by 24 hours of reperfusion. The AG-I group received AG (50 mg/kg) intraperitoneally four hours and 10 minutes before the induction of ischemia. The AG-II group received AG (50 mg/kg) intraperitoneally four hours and 10 minutes after the initiation of reperfusion. Serum urea and creatinine levels increased significantly in the I/R and AG-I groups compared to the control group. Kidney samples from rats in the I/R and AG-I groups revealed severe tubular damage at histopathological examination. Posttreatment with AG significantly reduced serum urea and creatinine levels and improved histopathological lesions compared with the I/R group. Although pretreatment with AG failed to protect kidneys against I/R injury in this experimental model, posttreatment with AG attenuated renal dysfunction and histopathological changes after I/R injury.     

前列腺癌组织中血管内皮生长因子的表达及其与内皮素-1的相关性研究

目的:探讨血管内皮生长因子(VEGF)在BPH及PCa中的表达和临床意义,及其与内皮素-1(ET-1)表达的关系。方法:应用免疫组织化学ElivisionTMplus法对44例前列腺癌和36例前列腺增生组织中VEGF和ET-1分别进行免疫组化染色,并在光镜下判断染色部位和染色强度。结果:VEGF在BPH和PCa组织中阳性表达率分别为69.4%和80.9%;阳染部位主要位于肿瘤和增生的腺上皮细胞,间质血管内皮细胞均强阳性;比较BPH和PCa的VEGF表达强度,两者有显著性差异(P<0.05);低分化PCa的ET-1表达强度显著高于中、低分化PCa(P<0.01);在骨转移(BM)PCa中VEGF表达强度显著高于非骨转移(non-BM)癌(P<0.01)。VEGF与ET-1的表达有显著的正相关性(rs=0.780,P<0.01)。结论:VEGF与PCa的发生发展有关,其过度表达可能在PCa的骨转移中起重要作用。VEGF与ET-1可能共同参与了PCa的发生发展。     

Nebivolol Reduces Experimentally Induced Warm Renal Ischemia Reperfusion Injury in Rats

Ischemia/reperfusion injury, which is commonly seen in the field of renal surgery or transplantation, is a major cause of acute renal failure. The objective of the present study was to examine the role of nebivolol in modulating peroxynitrite species-induced inflammation and apoptosis after renal warm ischemia/reperfusion injury in rats. The present study was designed to investigate the effects of nebivolol on the renal warm ischemia/reperfusion injury in rats treated with the nitric oxide synthase inhibitor, N^ω-nitro-L-arginine methyl ester. After right nephrectomy, nebivolol was administered for 15 days. On the 16^th day, ischemia was induced in contra lateral kidney for 45 min, followed by reperfusion for 24 hr. Renal function, inflammation, and apoptosis were estimated at the end of 24 hr reperfusion. Nebivolol improved the renal dysfunction and reduced inflammation and apoptosis after renal ischemia/reperfusion injury. In conclusion, nebivolol shows potent anti-apoptotic and anti-inflammatory properties due to its NO-releasing property. These findings may have major implications in the treatment of human ischemic acute renal failure.     

Cyclosporine Induces Endothelin-1 mRNA Synthesis and Nitric Oxide Production in Human Proximal Tubular Epithelial Cell Cultures

Background. Cyclosporine (CsA) is implicated in the development of chronic allograft nephropathy, which is related to reduced long-term allograft survival. The activation of tubular epithelial cells is involved in the renal scarring process via stimulation of factors such as endothelin-1 (ET-1) and nitric oxide (NO). The effect of CsA on the activation of tubular epithelial cells towards increased production of ET-1 and NO was investigated in this study. Methods. Human tubular epithelial cells (HK-2) were cultured in the presence of CsA at different concentrations (125, 250, 500, and 1,000 ng/mL). ET-1 m-RNA and NO production were measured using RT-PCR and Griess method, respectively. The cytotoxic effect of CsA was examined by the MTT method and cell count. Results. A statistically significant and dose-dependent cytotoxic effect of cyclosporine on HK-2 cells was observed. A dose-dependent up-regulation of ET-1 mRNA production and NO accumulation was observed under the influence of CsA. Conclusion. Increased synthesis of endothelin-1 mRNA and nitric oxide as well as a significant cytotoxic effect on tubular epithelial cells under the influence of CsA might be related to the development of CsA nephrotoxicity.     

Effect of exogenous l-arginine and ageing on NO and ET-1 in penile tissue of rat

The aim of this study was to investigate the effect and significance of l ‐arginine and ageing on nitric oxide (NO)‐cyclic guanosine monophosphate (cGMP) pathway and ET‐1 in penile tissue of rats. The different months old rats were divided into control group and experiment group randomly, the content of NO, cGMP, the changes of activity of Nitrous Oxide Systems (NOS) and the content of endothelin‐1(ET‐1) in penile tissue were determined. Along with ageing, NO and the activity of NOS in penile tissue increased at first and then decreased (P < 0.001). The content of cGMP reduced obviously (P < 0.001), the content of ET‐1 had a tendency to increase, and the ratio of ET‐1/NO increased significantly (P < 0.001 or P < 0.01). After feeding rats with l ‐arginine for some time, both the activity of NOS and the content of cGMP increased significantly in penile tissue (P < 0.001), while there was no obvious change in the content of ET‐1. Our study shows that whether the smooth muscle cells relax or contract might be decided by the content of cGMP and value of ET‐1/NO in penile tissue. l ‐arginine had significant effect on increasing the activity of NOS and the content of NO and cGMP, indicating that l ‐arginine has potential clinical value to be used in treating ED.     

一氧化氮合酶、内皮素在门脉高压大鼠肠粘膜中的表达变化

目的　探讨一氧化氮合酶和内皮素 -1在门脉高压大鼠肠粘膜中的表达情况。方法　2 0只雄性SD大鼠随机分为实验组与对照组 ,实验组行门静脉两步结扎加左肾上腺静脉结扎 ;应用免疫组化SP染色法检测iNOS、ecNOS及ET -1在大鼠小肠和结肠粘膜中的表达情况。结果　门静脉完全结扎后两周 ,实验组大鼠门静脉压力较对照组明显增高 ;iNOS、ecNOS及ET -1在小肠粘膜中表达强度较对照组增强 ,iNOS及ET -1在结肠粘膜中表达较对照组增强。结论　门脉高压大鼠小肠、结肠粘膜局部病变中iNOS、ecNOS及ET -1的表达不完全一致     

机械压力对人脐静脉内皮细胞ET-1、NO合成的影响和意义

目的探讨压力增高对血管内皮细胞分泌血管活性物质功能的影响及其在门静脉高压症发病机制中的作用。方法用RT-PCR方法半定量研究人脐静脉内皮细胞ET-1、eNOS、i-NOS mRNA的表达;用硝酸还原酶法检测各组细胞培养液中NO代谢产物NO2-/NO3-的含量,免疫荧光标记激光扫描共聚焦显微镜检测培养细胞的ET-1蛋白表达。结果ET-1和eNOS mR-NA在正常培养的内皮细胞中即有表达,iNOS mRNA则几乎无表达。生理水平压力刺激下各组各待测基因mRNA表达与对照组无显著性差异。超生理范围压力刺激后,ET-1 mRNA有显著性升高。eNOS mRNA在40 mm Hg 24 h后才有显著性差异。iNOS mRNA在不同条件下均无显著变化。在细胞培养液中分别加入细胞外钙螯合剂EGTA、PKC抑制剂后,则见ET-1、eNOS mRNA表达下降。结论压力增高可刺激血管内皮细胞合成ET-1、NO,其作用在转录水平,其作用机制分别与PKC信号通路和细胞外钙浓度有关。门静脉压力增高与血管内皮细胞合成ET-1、NO增多之间存在相互作用。     

内皮素-1单克隆抗体对肝移植缺血再灌注损伤保护作用的实验研究

目的: 探讨内皮素-1(ET-1)抗体对移植肝缺血再灌注损伤的保护作用.方法: 选用雄性SD大鼠108只,分为对照组、肝移植组与ET-1抗体组,观察应用抗ET-1单抗前后移植肝热缺血15 min,冷缺血40 min再灌注后第4小时血浆ET-1、丙氨酸转移酶(ALT)、透明质酸(HA)以及肝组织中ET-1和丙二醛(MDA)含量及肝组织病理学变化;同时,在移植肝再灌注后的第1,4,12,24小时观察ET-1的变化规律.结果: 移植肝缺血再灌注后,血浆和肝组织中ET-1,血浆HA,ALT和肝组织中MDA显著升高,而ET-1抗体组血浆和肝组织中ET-1,血浆HA,ALT和肝组织中MDA与肝移植组相比显著降低(P<0.01,P<0.05 ),且肝组织的淤血程度和损伤程度显著改善.结论: ET-1单克隆抗体对移植肝缺血再灌注损伤有保护作用.     

Endothelin-1 and Nitric Oxide in Patients on Chronic Hemodialysis

Aim. To establish the role of endothelin-1 and nitric oxide in the pathogenesis of hypertension in patients on chronic aemodyalisis by correlating endothelin-1 and NO plasma concentrations to the level of arterial hypertension with respect to angiotensin-converting enzyme (ACE) inhibitor therapy. Methods. We determined plasma concentrations of endothelin-1 and NO in patients on chronic hemodialysis (CHD) before and after hemodialysis treatment. The study included 30 CHD patients and 20 healthy participants as controls. Correlation to blood pressure was determined, as well as the effect of ACE inhibitors on the relationship between both endothelin-1 and NO in correlation with arterial hypertension. Main findings.Endothelin-1 plasma concentration was significantly higher in CHD patients before hemodialysis treatment than in healthy controls. Endothelin-1 plasma concentration was also significantly higher in CHD patients after hemodialysis than in healthy controls. There was a significant decrease in endothelin-1 plasma concentration after hemodialysis in comparison with its values before hemodialysis. In CHD patients, a positive correlation was found between endothelin-1 plasma concentration and systolic blood pressure after hemodialysis, irrespective of ACE inhibitors therapy. In CHD patients taking ACE inhibitors, systolic blood pressure increased with increasing endothelin-1 plasma concentration before as well as after hemodialysis. In patients taking ACE inhibitors, there was a tendency for diastolic blood pressure to increase with an increase in endothelin-1 plasma concentration after hemodialysis and to decrease with an increase in NO plasma concentration. Conclusion. NO and endothelin-1 play a significant role in etiology of the hemodynamic changes of blood pressure during the dialysis.     

复方黄芪首乌对肥胖大鼠肾组织ET-1/NOS的表达的干预作用

目的：探讨肥胖大鼠肾组织内皮素（ET-1）和一氧化氮（NO）平衡及中药复方黄芪首乌汤对其干预作用。方法：采用高糖高脂饲料喂养建立实验性肥胖大鼠模型,以复方黄芪首乌汤灌胃治疗,8周末采血检测血脂、血糖和肾功能,并取肾皮质匀浆检测ET-1和NOS含量,逆转录-聚合酶链反应检测肾组织ET-1和NOSmRNA表达。结果：复方黄芪首乌汤组大鼠体重显著下降,与苯那普利对照组结果相似（P〈0.05）;复方黄芪首乌汤能够明显降低肥胖大鼠血清LDL（P〉0.05）,但对实验大鼠的TC、TG和HDL-C作用不显著（P〉0.05）;复方黄芪首乌汤对实验大鼠血糖和Ins作用不明显（P〉0.05）;复方黄芪首乌汤能够下调实验鼠血肌酐和尿素氮水平（P〈0.05）;与正常组比较,肥胖大鼠肾组织NOS活力和基因表达水平显著下降,而ET-1及ET-1mRNA表达水平显著上升,经中药干预治疗后NOS及NOSmRNA表达上调,ET-1及ET-1mRNA表达下调。结论：复方黄芪首乌汤对大鼠肥胖具有一定的防治作用,可以减轻大鼠体重,调节血脂紊乱,保护肾脏功能,同时参与维持肾组织NO/ET-1动态平衡有关。