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| 1 | Cirrhotic portal hypertension: From pathophysiology to novel therapeutics显示文摘Portal hypertension and bleeding from gastroesophageal varices is the major cause of morbidity and mortality in patients with cirrhosis. Portal hypertension is initiated by increased intrahepatic vascular resistance and a hyperdynamic circulatory state. The latter is characterized by a high cardiac output, increased total blood volume and splanchnic vasodilatation, resulting in increased mesenteric blood flow. Pharmacological manipulation of cirrhotic portal hypertension targets both the splanchnic and hepatic vascular beds. Drugs such as angiotensin converting enzyme inhibitors and angiotensin Ⅱ type receptor 1 blockers, which target the components of the classical renin angiotensin system(RAS), are expected to reduce intrahepatic vascular tone by reducing extracellular matrix deposition and vasoactivity of contractile cells and thereby improve portal hypertension. However, these drugs have been shown to produce significant offtarget effects such as systemic hypotension and renal failure. Therefore, the current pharmacological mainstay in clinical practice to prevent variceal bleeding and improving patient survival by reducing portal pressure is non-selective-blockers(NSBBs). These NSBBs work by reducing cardiac output and splanchnic vasodilatation but most patients do not achieve an optimal therapeutic response and a significant proportion of patients are unable to tolerate these drugs.Although statins, used alone or in combination with NSBBs, have been shown to improve portal pressure and overall mortality in cirrhotic patients, further randomized clinical trials are warranted involving larger patient populations with clear clinical end points. On the other hand, recent findings from studies that have investigated the potential use of the blockers of the components of the alternate RAS provided compelling evidence that could lead to the development of drugs targeting the splanchnic vascular bed to inhibit splanchnic vasodilatation in portal hypertension. This review outlines the mechanisms related to the pathogenesis of portal hypertension and attempts to provide an update on currently available therapeutic approaches in the management of portal hypertension with special emphasis on how the alternate RAS could be manipulated in our search for development of safe, specific and effective novel therapies to treat portal hypertension in cirrhosis. | Lakmie S Gunarathne Harinda Rajapaksha Nicholas Shackel Peter W Angus Chandana B Herath | 2020 | World Journal of Gastroenterology2020，26，40： | 24 |
| 2 | 幽门螺杆菌治疗的新进展显示文摘幽门螺杆菌感染率高,致病性强。随着抗生素广泛大量的使用,幽门螺杆菌耐药率不断上升,同时不良反应也凸显出来,给临床抗菌治疗带来了困难,且其复发率高,故抗幽门螺杆菌感染一直是研究领域中的重点及热点。标准三联疗法或四联疗法对幽门螺杆菌控制不佳,但以益生菌联合抗菌药物等新疗法为根除幽门螺杆菌带来了新的希望。 | 郑晓文 李强 王玉平 周永宁 | 2016 | 医学综述2016，22，7： | 16 |
| 3 | 肾素-血管紧张素系统在非酒精性脂肪肝发病中的作用显示文摘 | 汪亮 张霞 | 2010 | 重庆医学2010，39，22： | 12 |
| 4 | Therapeutic potential of targeting the renin angiotensin system in portal hypertension显示文摘Portal hypertension is responsible for the bulk of the morbidity and mortality in patients with cirrhosis.Drug therapy to reduce portal pressure involves targeting two vascular beds.The first approach is to reduce intra hepatic vascular tone induced by the activity of powerful vasocontrictors such as angiotensin Ⅱ,endothelin-1 and the sympathetic system and mediated via contraction of perisinusoidal myofibroblasts and pervascular smooth muscle cells.The second approach is to reduce mesenteric and portal blood flow.Non-selective b-blockers are widely used and have been shown to prolong patient survival and reduce oesophageal variceal bleeding in advanced cirrhosis.However many patients are unable to tolerate these drugs and they are ineffective in a significant proportion of patients.Unfortunately there are no other drug therapies that have proven efficacy in the treatment of portal hypertension and prevention of variceal bleeding.This review briefly outlines current therapeutic approaches to themanagement of portal hypertension,and the evidence supporting the role of the renin angiotensin system(RAS) and the use of RAS blockers in this condition.It will also outline recent advances in RAS research that could lead to the development of new treatments focusing in particular on the recently discovered 'alternate axis' of the RAS. | Chandana B Herath Josephine A Grace Peter W Angus | 2013 | World Journal of Gastrointestinal Pathophysiology2013，4，1： | 9 |
| 5 | 慢性乙型肝炎和肝硬化患者AngⅡ、Ang(1-7)及AngⅡ/Ang(1-7)比值的变化显示文摘目的研究慢性乙型肝炎和肝硬化患者肾素-血管紧张素系统(RAS)中血管紧张素Ⅱ(AngⅡ)、血管紧张素(1-7)[Ang(1-7)]及AngⅡ/Ang(1-7)比值的变化,探讨其在肝纤维化发病过程中的意义。方法收集20例慢性乙型肝炎患者、60例乙型肝炎肝硬化患者和20例健康对照者的一般临床资料及血浆标本,采用酶联免疫吸附法测定血浆中AngⅡ、Ang(1-7)的水平,分析AngⅡ、Ang(1-7)及AngⅡ/Ang(1-7)在各组之间的表达差异。结果肝硬化患者血浆AngⅡ、Ang(1-7)水平及AngⅡ/Ang(1-7)比值分别为(105.88±53.56)pg/ml,(77.95±27.43)pg/ml,1.34±0.48,均显著高于乙型肝炎组和对照组[(59.98±12.97)pg/ml、(21.53±18.27)pg/ml,(62.45±11.24)pg/ml、(27.06±12.76)pg/ml,0.97±0.16、0.72±0.39;均P<0.01];肝硬化患者Child-Pugh A级至C级AngⅡ、Ang(1-7)水平及AngⅡ/Ang(1-7)的比值逐渐升高,各组之间差异有统计学意义(P<0.05);AngⅡ/Ang(1-7)比值与Child-Pugh评分呈正相关(r=0.499,P<0.01)。结论随着肝纤维化或肝硬化患者的病情进展,AngⅡ/Ang(1-7)的比值逐渐增加,其水平对慢性肝病患者的病情评估具有指导意义。 | 杨志花 申凤俊 黄会芳 | 2016 | 中华临床医师杂志(电子版)2016，10，8： | 6 |
| 6 | 缬沙坦对肝纤维化大鼠ACE2、AngⅡ、Ang(1-7)的影响显示文摘目的研究缬沙坦对肝纤维化大鼠肝组织血管紧张素转化酶2(ACE2)表达,血管紧张素Ⅱ(AngⅡ)、血管紧张素(1-7)[Ang(1-7)]水平,AngⅡ/Ang(1-7)比值的影响。方法制备复合因素法诱导的大鼠肝纤维化模型,将34只大鼠随机分为3组,正常对照组10只,模型组12只,缬沙坦组12只。造模成功后测定各组大鼠的门静脉压力,并将肝组织进行HE及Masson染色,免疫组化法检测肝组织ACE2的表达,酶联免疫法测定肝匀浆AngⅡ、Ang(1-7)的水平。结果缬沙坦组门静脉压力(PVP)较模型组明显降低(P<0.01),平均动脉压(MAP)、心率(HR)无明显变化;与正常对照组比较,模型组ACE2表达,AngⅡ、Ang(1-7)水平(P<0.01)及AngⅡ/Ang(1-7)比值(P<0.01)均升高;与模型组比较,缬沙坦组ACE2表达及Ang(1-7)水平进一步升高(P<0.05),而AngⅡ无明显变化,AngⅡ/Ang(1-7)比值降低(P<0.05)。结论缬沙坦可降低肝纤维化门静脉压力,其抗肝纤维化,间接降低门脉压力的作用机制可能与该药能够上调ACE2、Ang(1-7)的水平及降低AngⅡ/Ang(1-7)比值有关。 | 孙丽萍 霍丽娟 张彦莹 | 2013 | 国际消化病杂志2013，33，2： | 3 |
| 7 | 紧密连接蛋白与幽门螺杆菌感染相关性胃病的关系研究显示文摘幽门螺杆菌(Hp)感染是导致慢性胃炎、消化性溃疡的重要原因,但其发病机制尚不清楚。紧密连接结构和功能受损导致胃黏膜屏障功能障碍在Hp相关性胃病发病中的作用近年来受到关注。紧密连接由多种蛋白及分子组成,包括3种完整的膜蛋白(咬合蛋白、闭合蛋白、连接黏附分子)和1种胞浆蛋白(闭合小环蛋白)。该文主要阐述各种紧密连接蛋白的组成及功能,Hp感染所致紧密连接蛋白功能的变化及其与相关胃病发病的关系,以及增强紧密连接蛋白功能在Hp相关性胃病防治中的意义。 | 李炜 江米足 | 2014 | 中国当代儿科杂志2014，16，3： | 2 |
| 8 | 非肌肉肌球蛋白Ⅱ研究进展显示文摘非肌肉细胞中存在的肌球蛋白Ⅱ称为非肌肉肌球蛋白Ⅱ(non-muscle myosinⅡ,NMⅡ),与肌肉中肌球蛋白Ⅱ具有类似的化学结构,其活性受自身轻链和重链磷酸化水平调节。除了作为一种分子马达为细胞内各种分子运动提供动力外,NMⅡ还参与细胞迁移、黏附、胞质分裂等各种生理活动。 | 张洪峰 彭军 | 2012 | 中国药理学通报2012，28，1： | 2 |
| 9 | 贝那普利对肝纤维化大鼠Ang-(1-7)、ACE2及Mas受体mRNA的影响显示文摘目的观察血管紧张素转换酶抑制剂(ACEI)贝那普利抗大鼠肝纤维化的疗效,研究贝那普利对肝纤维化大鼠肝组织血管紧张素-(1-7)[Ang-(1-7)]、血管紧张素转换酶2(ACE2)m RNA及Mas受体m RNA的影响。方法制备四氯化碳(CCl4)诱导的大鼠肝纤维化模型,同时应用贝那普利灌胃,共8w。对肝组织进行常规HE及Masson染色,ELISA测定肝匀浆血管紧张素Ⅱ(AngⅡ)、Ang-(1-7)浓度,计算AngⅡ/Ang-(1-7)比值,实时荧光定量PCR测定肝组织ACE2m RNA和Mas受体m RNA的水平。结果造模6、8周末,贝那普利治疗组大鼠的肝纤维化程度均较模型组减轻;肝匀浆AngⅡ的浓度较模型组降低(P<0.05),肝匀浆Ang-(1-7)的浓度较模型组增加(P<0.05),肝匀浆AngⅡ/Ang-(1-7)的比值较模型组降低(P<0.05);贝那普利治疗组肝组织ACE2及Mas受体m RNA的水平均较模型组增加(P<0.05)。结论贝那普利具有良好的抗肝纤维化作用,其机制可能与AngⅡ浓度降低,Ang-(1-7)浓度增加,AngⅡ/Ang-(1-7)比值降低有关,亦可能与ACE2和Mas受体表达增加有关。 | 丁少华 申凤俊 王丽华 | 2017 | 当代医学2017，23，15： | 1 |
| 10 | 脂氧素受体激动剂BML-111对大鼠急性肝损伤的干预作用及其机制显示文摘目的:探索脂氧素对急性肝损伤的作用及机制。方法:SD大鼠24只随机分为4组(n=6):正常对照组:皮下注射橄榄油,剂量1.8 ml/kg。模型组:皮下注射40%四氯化碳(CCL4)油剂(橄榄油为溶剂),剂量3 ml/kg。BML-111治疗组:皮下注射Lipoxin受体激动剂BML-111,剂量1 mg/kg,30 min后处理同模型组。BOC-2阻断剂组:皮下注射Lipoxin受体阻断剂BOC-2,剂量50μg/kg,30 min后处理同BML-111组。HE染色观察肝组织病理学变化,判断肝损伤情况。血清学检测血清谷丙转氨酶(ALT)及谷草转氨酶(AST)活性;试剂盒法检测大鼠肝组织中髓过氧化物酶(MPO)活性;ELISA法测定血清中血管紧张素转化酶(ACE)、血管紧张素转化酶2(ACE2)、血管紧张素II(AngII)、血管紧张素1-7(Ang-(1-7))的含量。Western blot检测肝组织中Ang II、Ang-(1-7)的蛋白含量。结果:治疗组较模型组和阻断剂组的肝损伤程度减轻;BML-111降低CCL4损伤的大鼠血清中ACE、AngII的含量(P<0.01)及升高血清中ACE2、Ang-(1-7)的含量(P<0.01)。BML-111增加肝组织中Ang-(1-7)含量,降低CCL4损伤的大鼠组织中AngII含量。结论:结果表明脂氧素受体激动剂BML-111对大鼠急性肝损伤的干预作用及其机制,可能与调节AngII和Ang-(1-7)有关。 | 胡泉东 杨玉娟 余珊珊 | 2020 | 中国应用生理学杂志2020，36，5： | 1 |
| 11 | 大鼠肝硬化形成过程中肝组织AngⅡ/Ang(1-7)的动态变化显示文摘目的研究大鼠肝硬化形成过程中肝组织血管紧张素Ⅱ(AngⅡ)、血管紧张素(1-7)[Ang(1-7)]水平及AngⅡ/Ang(1-7)比值的变化。方法复合因素法制备大鼠肝硬化模型,将33只大鼠随机分为正常组6只,模型组27只,分别于造模第2、4、6、8周末处死模型组大鼠各6只,并对各组大鼠肝组织进行HE及Masson染色,酶联免疫法测定肝组织匀浆AngⅡ、Ang(1-7)的水平。结果随着大鼠肝纤维化程度进行性加重,AngⅡ、Ang(1-7)水平均呈上升趋势(P<0.05);2、4周模型组AngⅡ/Ang(1-7)比值较8周模型组降低(P<0.05)。结论大鼠肝硬化的发生发展可能与AngⅡ和Ang(l-7)失衡有关。 | 孙丽萍 霍丽娟 张彦莹 | 2012 | 当代医学2012，18，12： | 0 |
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