Corrigendum: Astrocytic endothelin-1 overexpression impairs learning and memory ability in ischemic stroke via altered hippocampal neurogenesis and lipid metabolism

In the article titled“Astrocytic endothelin-1 overexpression impairs learning and memory ability in ischemic stroke via altered hippocampal neurogenesis and lipid metabolism,”published on pages 650-656,Issue 3,Volume 19 of Neural Regeneration Research(Li et al.,2024),there were two errors that needed to be corrected.

Effects of PEAR1 gene polymorphism on big endothelin-1 levels in Chinese patients with acute myocardial infarction after percutaneous coronary intervention

Acute myocardial infarction (AMI) has been associated with poor prognosis,even after revascularization with percutaneous coronary intervention (PCI),likely due to coronary endothelial cell dysfunction and injury.^([1,2])Endothelin-1 (ET-1),a peptide that serves as a vasoconstrictor of smooth muscle cell proliferation,can reflect endothelial cell functional states.Due to low circulation levels and short plasma half-life time,measuring plasma ET-1 levels is difficult.In contrast,big ET-1.

Pharm Web网站及其药学信息资源的检索与利用

对互联网上重要的药学信息资源网站PharmWeb及其涵盖的相关资源进行研究,对其特征进行分析,并对其检索方法进行介绍。

内皮素(Endothelin)对大鼠心血管功能的影响

给正常大鼠静脉注射3μg/Kg内皮素,可引起动脉血压下降和心肌收缩力减弱,使LVPSP和±LV dP/dtmax呈显著而持久的降低。给利血平和阿托品化的大鼠注射同样剂量的内皮素,使血压一过性升高。用不同剂量的内皮素灌流心脏,可引起冠状动脉收缩,使灌流压升高,并有强大的抑制心功能的作用,使LVPSP和±LV dp/dt max显著降低,且具有剂效关系。在浓度为10^(-8)M时,可出现心肌挛缩和心律失常,内皮素具有强大的收缩主动脉环的作用,其ED_(50)为3×10~8M,较NE强约5倍。提示内皮素可能是在机体严重损伤(如休克、缺血、缺氧)等条件下,血管内皮细胞产生、释放或漏出的一种致病因子,参与某些疾病的发病过程。

VEGF、Endostatin、Endothelin-1在大肠腺瘤及大肠癌中的表达及意义

目的探讨大肠腺瘤及大肠癌中血管内皮生长因子(VEGF)、内皮抑素(Endostatin)、内皮素(Endothelin-1)的表达与病理组织学特征的关系以及三者之间的关系及意义,并分析三者在大肠腺瘤癌变过程中的相互作用。方法分别应用聚合酶链式反应PCR法和免疫组织化学SP法,联合检测VEGF、Endostatin、Endothelin-1在20例大肠腺瘤、40例大肠癌及20例正常大肠组织中的表达情况,并分析其与大肠腺癌临床病理特征之间的关系。结果①在正常大肠组织、大肠腺瘤及大肠癌中,VEGF、Endothelin-1的阳性表达率呈依次递增,VEGF、Endothelin-1在大肠腺癌与正常大肠黏膜之间差异有显著性(P<0.01);Endostatin在正常大肠组织、大肠腺瘤及大肠癌中的阳性表达率呈依次递减,在大肠腺癌与正常大肠粘膜之间差异有显著性(P<0.01);②40例大肠腺癌中,VEGF、Endothelin-1的阳性表达率与肿瘤分化程度、浸润深度、淋巴结转移及远处转移密切相关,Dukes C+D期组高于Dukes A+B期组(P<0.05﹚;Endostatin表达与肿瘤分化程度、浸润深度、淋巴结转移及远处转移呈负相关,Dukes C+D期组低于Dukes A+B期组(P<0.05﹚。结论随着大肠癌的发生发展,VEGF、Endothelin-1的阳性表达率依次增加,提示可作为大肠腺癌发生发展的分子标志,二者在大肠腺癌的发生发展过程中可能具有协同促进作用;两者在大肠腺癌中的表达高于大肠腺瘤组,表明两者在腺瘤向腺癌转变的部分分子机制中起着重要作用。随着大肠腺癌的发生发展,Endostatin的表达逐渐降低,腺癌组低于腺瘤组,提示Endostatin在大肠癌的发生发展、腺瘤癌变的过程中可能受到抑制。联合检测VEGF、Endothelin-1和Endostatin的表达对筛选高危大肠腺瘤、判断大肠癌的发生发展、转移及预后具有重要的参考价值。

Endothelin-1诱导的大鼠局灶性脑缺血再灌注模型

目的 研究Endothelin 1(ET 1)诱导的大鼠局灶性脑缺血再灌注模型。方法 将ET 1注入大脑中动脉 (MCA)附近 ,ET 1强烈的缩血管作用可使脑血流 (CBF)降低造成缺血性脑损伤 ,采用氢清除法监测缺血过程中大鼠纹状体脑血流的变化 ,于缺血后 6h进行神经功能评分 ,并采用TTC染色法观察脑梗死面积的变化。结果 ET 1可使纹状体血流呈现浓度依赖性的降低 ,10min时CBF降至最低 ,分别为 :ET 130 0 pmol组 (2 7 1± 2 9) %、36 0pmol组 (12 7±2 1) %、4 0 0pmol组 (11 9± 1 8) %、5 0 0 pmol组 (9 5±1 6 ) % ;神经功能评分显示ET 1可造成大鼠不同程度的神经功能损伤 ;MCAO后 2 4h ,脑梗死面积百分率随ET 1浓度的增加而呈上升趋势 ,并显示出良好的浓度依赖关系 :30 0pmol组 (3 9± 0 3) %、36 0 pmol组 (7 4± 0 5 ) %、4 0 0 pmol组 (11 3± 1 3) %、5 0 0 pmol组 (16 2± 1 8) % ;r =0 992 6(P <0 0 5 )。结论 该模型操作简单 ,造成的脑梗死范围稳定、重现性好 。

参照美国Pharm.D.模式的临床药学教学模式探索

目的:探索我国药学本科生临床药学课程的教学、培养模式。方法:参照美国Pharm.D.教学模式,向31名药学本科生授课并以案例分析实践形式进行强化训练,课后以问卷形式调查学生对学习效果与教学方式的反馈。结果:学生在课堂上有较好的互动,对课堂内容掌握程度较高。问卷调查结果显示,学生自认为学习效果一般(3.47/5)而对于教学方法的认可度较高(4.13/5)。结论:理论学习结合案例学习的教学方式可行性高,值得推广。

CLINICAL RESEARCH OF IMPACTS ON PLASMA ENDOTHELIN AND INTELLIGENCE IN MULTI-INFARCT DEMATIA TREATED WITH CLUSTER PRICKING ON HEAD POINTS

Objective To probe into the impacts on the therapeutic effects and endothelin （ET） in multi-infarct dementia （MID） treated with cluster pricking on head points.Methods 60 cases of MID were randomized into acupuncture group and western medicine group,treated with cluster pricking on head points and huperzien A tablet respectively.Plasma ET lever,HDS,ADL and CNFDS （clinical neurological functional defect scoring） were determined before treatment,and the statistical analysis showed that there were no significant difference （P〉0.05）.Results In 8-week treatment,ET level in both groups were decreased,but it was decreased much more obviously in acupuncture group,indicating significant difference in the statistical comparison （P〈0.05）.The scores of HDS and ADL were all up in acupuncture and western medicine groups,but the significant statistical difference was obtained in the comparison between acupuncture group and western medicine group （P〈0.05）.In acupuncture group,the result of CNFDS was much down comparing with that before the treatment,indicating significant difference （P〈0.05）;but in western medicine group,there was no significant difference in CNFDS before and after treatment （P〉0.05）,suggesting that acupuncture reduces CNFDS of MID patient,neither for western medicine.Conclusion Cluster pricking on head points improves the intelligence of MID patient,reduces ET level and grades up HDS and ADL,moreover,it reduces CNFDS of MID patients and releases the symptoms.

难治性胃溃疡患者血浆Endothelin-1浓度检测的意义

目的:检测难治性胃溃疡患者血浆Endothe lin-1水平,探讨其在难治性溃疡发病中的作用。方法:64例胃溃疡病患者给予正规抗溃疡病治疗,其中34例12周后经胃镜证实溃疡未愈合(难治性溃疡组);30例痊愈(溃疡愈合组)。分别检测两组患者治疗前后的血浆ET-1水平,20例健康体检者作为对照组。结果:治疗前,难治性溃疡组的平均血浆浓度(62.71±12.38)μg/L,显著低于溃疡愈合组(96.39±15.25)μg/L及健康对照组(86.29±11.23)μg/L),差异均有显著性(P<0.05),溃疡愈合组与对照组间差异无显著性。两组患者治疗前后的ET-1水平均无显著性变化。结论:难治性溃疡患者的ET-1水平偏低,可能导致新生血管的形成不足使得溃疡久治不愈。

我国“博士专业学位”与美国“专业博士”辨析——兼论美国药学博士(Pharm.D.)教育层次

对中国"博士专业学位"与美国"专业博士"概念内涵进行梳理,发现美国"专业博士"包括"普通职业型博士学位"和"第一职业学位中的博士学位",其概念范畴大于中国"博士专业学位"。进一步研究发现,美国"专业博士"中"第一职业学位中的博士学位"的教育层次并不一定是国际教育标准分类中的博士层次教育(ISCED8级),而是硕士层次教育(ISCED7级),并以美国药学博士(Pharm.D.)为例进行了实证研究。最后提出中国高等教育在国际化进程中要深入探寻国外学位层次的"本质内涵",避免掉进名称直译的"表象误区"。

Plasma endothelin and nitric oxide levels in patients with acute pancreatitis

Objective: To explore the changes of plasma endothelin(ET) and nitric oxide (NO) levels in patients with a-cute pancreatitis.Methods: The level of plasma ET was measured by ra-dioactive-immunoassay, and NO by spectrophotometry.Results: The levels of ET, NO and the ET/NO ratioin patients with severe acute pancreatitis(SAP) within24 hours in hospital were all significantly higher thanthose in other groups of patients [(176±8)pg/ml,(97±11) μmol/L, and 1.83±0.12, P<0.01]. Com-pared to healthy controls(N), the levels of ET and NOin patients without pancreatitis acute abdomen (NAP)and patients with mild acute pancreatitis (MAP) in-creased significantly (P<0.01). After appropriate treat-ment, the levels of ET and NO in the MAP groupwere lower (P<0.01). Compared with those beforetreatment, the levels of ET and NO in the SAP groupon the 3rd and 7th day in hospital dropped signifi-cantly(P<0.01).The ET/NO ratio on the 7th daywas also lower than that on admission (P<0.01).Conclusions: The malfunction of endothelial cells andthe increased ET/NO ratio may be related to the mecha-nism of pancreatic microcirculatory disturbance in pa-tients with SAP; early dynamic determination of theseparameters may help predict the prognosis of SAP.

Effects of endotoxin on endothelin receptor in hepatic and intestinal tissues after endotoxemia in rats

INTRODUCTIONEndothelins(ETs) has a potent and sustainedvasoconstrictive effect on a variety of blood vessels.The vascular smooth muscle cell (VSMC)is thetarget for ETs.VSMC of the whole body containsendothelin receptor (ETR).A great number ofexperiments have shown that three distinctcomplementary DNAs of ETR have been identifiedi.e.,endothelin A receptor(ET_A receptor),endothelin B receptor(ET_B receptor)

Increased endothelin receptor B and G protein coupled kinase-2 in the mesentery of portal hypertensive rats

AIM: To elucidate the mechanisms of mesenteric vasodilation in portal hypertension (PHT), with a focus on endothelin signaling. METHODS: PHT was induced in rats by common bile duct ligation (CBDL). Portal pressure (PP) was measured directly via catheters placed in the portal vein tract. The level of endothelin-1 (ET-1) in the mesenteric circulation was determined by radioimmunoassay, and the expression of the endothelin A receptor (ETAR) and endothelin B receptor (ETBR) was assessed by immunofluorescence and Western blot. Additionally, expression of G protein coupled kinase-2 (GRK2) and β-arrestin 2, which influence endothelin receptor sensitivity, were also studied by Western blot. RESULTS: PP of CBDL rats increased significantly (11.89 ± 1.38 mmHg vs 16.34 ± 1.63 mmHg). ET-1 expression decreased in the mesenteric circulation 2 and 4 wk after CBDL. ET-1 levels in the systemic circulation of CBDL rats were increased at 2 wk and decreased at 4 wk. There was no change in ETAR expression in response to CBDL; however, increased expression of ETBR in the endothelial cells of mesenteric arterioles and capillaries was observed. In sham-operated rats, ETBR was mainly expressed in the CD31+ endothelial cells of the arterioles. With development of PHT, in addition to the endothelial cells, ETBR expression was noticeably detectable in the SMA+ smooth muscle cells of arterioles and in the CD31+ capillaries. Following CBDL, increased expression of GRK2 was also found in mesenteric tissue, though there was no change in the level of β-arrestin 2. CONCLUSION: Decreased levels of ET-1 and increased ETBR expression in the mesenteric circulation following CBDL in rats may underlie mesenteric vasodilation in individuals with PHT. Mechanistically, increased GRK2 expression may lead to desensitization of ETAR, as well as other vasoconstrictors, promoting this vasodilatory effect.

美国Pharm.D.岗位胜任力培养模式及对临床中药学人才培养的思考

以美国内布拉斯加医学中心(University of Nebraska Medical Center,UNMC)岗位胜任力为导向培养Pharm.D.为例,介绍了其灵活多样的课堂教学方法、丰富充实的实践课程、注重人文素质培养的教育理念。临床中药学作为一门新兴的医药交叉学科,对人才的培养存在一些不足,建议结合美国Pharm.D.培养的先进经验,构建符合学科特色的临床中药学人才培养体系,培养优秀的临床中药学人才,为中医药事业的持续发展做出贡献。

Plasma endothelin in patients with endotoxemia and dynamic comparison between vasoconstrictor and vasodilator in cirrhotic patients

INTRODUCTIONPortal hypertension is a common clinical syndromecharacterized by an abnormal increase in portalblood to the systemic circulation, bypassing theliver. Recent studies have reported that humoralsubstances play an important role in thepathogenesis of portal hypertension, either byincreasing vascular resistance at both theintrahepatic and porto-collateral sites or affectingsplanchnic vasodilation with a concomitant increasein parto-collateral blood flow[1-6]

Portopulmonary hypertension and serum endothelin levels in hospitalized patients with cirrhosis

BACKGROUND:Cirrhosis is associated with several extrahepatic manifestations including portopulmonary hypertension (PPHT).Recent data suggest that endothelins (ETs) are related to the pathophysiology of PPHT.The study aimed to measure serum ET levels in hospitalized cirrhotic patients and to determine their association with PPHT and patient outcome.METHODS:Fifty-seven cirrhotic patients [43 males;median age 58 (28-87) years] underwent Doppler echocardiography.Patients with systolic pulmonary arterial pressure ≥40 mmHg and pulmonary acceleration time <100 ms were deemed to have PPHT.ET-1,2,and 3 serum levels were measured with an ELISA assay.All-cause mortality was recorded over a median period of 24 months.RESULTS:Nine out of 57 patients (15.8%) had PPHT.Among various clinical variables,only autoimmune hepatitis was associated with PPHT (OR=11.5;95% CI,1.58-83.4;P=0.01).ET-1 levels [9.1 (1.6-20.7) vs 2.5 (1.4-9.2) pg/mL,P=0.02] and the ET-1/ET-3 ratio [4.73 (0.9-22.4) vs 1.6 (0.3-10.7),P=0.02] were significantly higher in patients with PPHT than in those without.ET-2 and ET-3 levels did not differ between the two groups.There was no difference in survival between the two groups,although ET-1 levels were associated with an adverse outcome in Cox regression analysis (HR=1.11;95% CI,1.02-1.22;P=0.02 per unit increase in ET-1).CONCLUSION:Our data suggest that ET-1 and the ET-1/ET-3 ratio are elevated in patients with PPHT and that ET-1 is associated with a poor outcome irrespective of PPHT.

Melatonin abates liver ischemia/reperfusion injury by improving the balance between nitric oxide and endothelin

BACKGROUND: Melatonin exerts complex physiological and pharmacological effects on multiple systems and organs. We hypothesized that melatonin might abate ischemia/ reperfusion (I/R) injury in the liver by inhibiting excessive oxidative stress and keeping nitric oxide (NO) from being scavenged by free radicals. The aim of the present study was to investigate whether melatonin protects the liver from I/R injury and, if so, by what underlying mechanism. METHODS: Under anesthesia, Wistar rats were intraperi- toneally injected with 20 mg/kg melatonin (dissolved in physiological saline containing 4% ethanol, Mel group), 4% alcohol (Alc group), or physiological saline (NS group). The artery, portal vein and bile duct of the left lobe of the liver were clamped for 60 minutes and then released. At different time points after I/R, the rats were sacrificed and blood samples were collected to measure the levels of serum alanine aminotransferase (ALT), lactic dehydrogenase (LDH), and NO. Hepatic tissue samples were collected for measuring endothelin expression by immunohistochemical staining and for routine morphological and histological examination. RESULTS: The levels of both ALT and LDH in the Mel group were significantly reduced for up to 24 hours after I/R compared with the Alc and NS groups (P<0.05). The levels of NO in the Mel group were significantly elevated for up to 12 hours after I/R relative to the NS group (P<0.05). The NO levels were also elevated at 0.5 and 6 hours after I/R in the Alc group (P<0.05). The immunohistochemical staining of hepatic tissue showedthat endothelin-positive cells were significantly fewer in the Mel group than in the Alc and NS groups at 6 hours after I/R (P<0.01). The necrosis of hepatocytes and the destruction of hepatic cords in the Alc and NS groups were greatly improved in Mel-treated rats, which is in concert with our functional data. CONCLUSIONS: Pretreatment with melatonin increased NO bioavailability and decreased endothelin expression, and consequently played a protective role in preserving both liver function and structure during ischemia and reperfusion injury.

牦牛Endothelin-1基因CDS序列克隆及其真核表达质粒构建

Endothelin-1主要通过促进血管平滑肌细胞增殖引起血管结构和功能的改变,从而刺激血管收缩,Endothelin-1在动物血管生成和低氧适应等关键发育和生理过程中发挥重要的作用。为了进一步探讨高原动物脑Endothelin-1对其极端低氧适应调控的分子机理,本研究对牦牛(Bos grunniens)脑Endothelin-1基因CDS全长序列进行了克隆及其真核表达载体的构建。结果表明,牦牛Endothelin-1基因的CDS全长序列含有一个609 bp的开放阅读框,编码202个氨基酸,该蛋白分子量为22.98 k Da,理论等电点(p I)为9.63;成功构建出带有CMV启动子,绿色荧光蛋白标记的牦牛Endothelin-1真核表达质粒p EGFP-C1-Endothelin-1;牦牛Endothelin-1基因CDS全长序列编码的氨基酸序列与黄牛(Bos taurus)、藏羚羊(Pantholop shodgsoni)、绵羊(Ovis aries)、野猪(Sus scrofa)、小鼠(Mus musculus)、人(Homo sapiens)的同源性分别为100%、95%、93%、81%、77%、70%;且该氨基酸序列的系统进化情况与其亲缘关系远近一致。因此,我们认为高原动物牦牛Endothelin-1的结构和功能在进化上均具有高度保守性,其在低氧适应中的作用可能是通过表达差异或转录后修饰实现的,且本研究构建的真核表达质粒为进一步探讨该基因在青藏高原动物脑对极端低氧生境适应中的生物学功能及其调控机理提供了支持。

Associations of big endothelin-1 and C-reactive protein in atrial fibrillation

Background Atrial fibrillation （AF） is associated with inflammation and endothelial dysfunction. However, the association between inflammation （as indexed by high-sensitivity C-reactive protein, hs-CRP） and endothelial function [as indexed by big endothelin-1 （ET-1）] in AF patients remains unclear. Methods We enrolled 128 patients with lone AF, among which 83 had paroxysmal AF, and 45 had persistent AF. Eighty-two age- and gender-matched controls of paroxysmal supraventricular tachycardia without AF history were evaluated. Plasma hs-CRP, big ET-1 levels and other clinical characteristics were compared among the groups. Results Patients with persistent AF had higher hs-CRP concentrations than those with paroxysmal AF （P 〈 0.05）, both groups had higher hs-CRP level than controls （P 〈 0.05）. Patients with persistent AF had higher big ET-1 level than those with paroxysmal AF, although the difference did not reach the statistical significance （P 〉 0.05）, and both groups had higher big ET-1 levels than controls （P 〈 0.05）. Multiple regression analyses revealed hs-CRP as an inde- pendent determinant of AF （P 〈 0.001）. Further adjusted for big ET-1, both big ET-1 and hs-CRP were independent predictors for AF （P 〈 0.001）, but the odds ratio for hs-CRP in predicting AF attenuated from 8.043 to 3.241. There was a positive relation between hs-CRP level and big ET-1 level in paroxysmal AF patients （r = 0.563, P 〈 0.05）, however, the relationship in persistent AF patients was poor （r = 0.094, P 〈 0.05）. Conclusions Both plasma hs-CRP and big ET-1 levels are elevated in lone AF patients, and are associated with AF. In paroxysmal lone AF patients, there were significant positive correlations between plasma hs-CRP level and big ET- 1 level.

Effect of Astragalus on the Endothelin in Rats with AcuteLung Injury

The effect of astragalus on the endothelin in serum and lung of the rats with acute lung injury was studied. The results demonstrated that the concentration of endothelin in the lung of the rats in therapy group was lower than that of the injured rats (64.36±5.37 ng/L vs 103.32±4.99 ng/L, P <0.001), and level of serum endothelin was also lower than that of the injured rats (85.35 ng/L vs 113.35 ng/L, P <0.01). PaO 2, serum SOD, lung coefficient, ratio of lung wet weight/dry weight in two groups were also significantly different ( P <0.01) respectively, and the lung pathological injury in the treatment group were less than that of injury group. So it is concluded that astragalus could inhibit the increase of serum and lung endothelin, thereby playing a protective role in the rats with acute lung injury.