目的探究血管紧张素(1-7)[angiotensin-(1-7),Ang-(1-7)]及线粒体组装受体(mitochondrial assembly of receptor,MasR)在子宫内膜癌中的表达及相关性。方法选取河北北方学院附属第一医院2017年4月~2019年4月治疗的16例正常子宫内膜组织...目的探究血管紧张素(1-7)[angiotensin-(1-7),Ang-(1-7)]及线粒体组装受体(mitochondrial assembly of receptor,MasR)在子宫内膜癌中的表达及相关性。方法选取河北北方学院附属第一医院2017年4月~2019年4月治疗的16例正常子宫内膜组织,32例子宫内膜不典型增生组织和78例手术切除的子宫内膜癌组织,共126例。使用酶联免疫吸附法(ELISA)检测Ang-(1-7),Western blot检测MasR在组织中的表达情况。结果三组组织中,正常子宫内膜组织内Ang-(1-7)(χ^(2)=11.506,P=0.000)和MasR(χ^(2)=8.619,P=0.002)阳性率最低,子宫内膜癌组阳性率最高,差异均具有统计学意义。与另外两组相比,子宫内膜癌组Ang-(1-7)和MasR表达显著增高。Ang-(1-7),MasR表达水平和子宫内膜癌肿瘤分期(t≥2.82,P=0.001)、转移(F=33.35和13.80,P=0.000)及分化程度(t≥2.82,P=0.029)均有相关性。结论Ang-(1-7)及MasR参与了子宫内膜癌新生血管的生成,其表达增高可促发癌细胞增长,可用于治疗及预后子宫内膜癌的新靶点。展开更多
目的研究奥美沙坦对肾血管性高血压大鼠心肌肥厚的作用,探讨其对病理性肥厚心肌ACE2/Ang(1-7)/Mas的作用。方法清洁级雄性SD大鼠68只,随机分为假手术组(S)18只、两肾一夹组(two kidney one clip,2K1C)50只。S组分离左肾动脉而不缩窄;实...目的研究奥美沙坦对肾血管性高血压大鼠心肌肥厚的作用,探讨其对病理性肥厚心肌ACE2/Ang(1-7)/Mas的作用。方法清洁级雄性SD大鼠68只,随机分为假手术组(S)18只、两肾一夹组(two kidney one clip,2K1C)50只。S组分离左肾动脉而不缩窄;实验组采用2K1C方法制备高血压模型。术后第4周末采用尾动脉袖法测量大鼠血压,造模成功大鼠(44只)随机分为2K1C+蒸馏水组(K)22只与2K1C+奥美沙坦组(O)22只。术后第5周始O组以奥美沙坦3mg.kg-1.d-1灌胃;K组每天以等体积蒸馏水灌胃。术后第8、12、14周,测量大鼠血压,超声心动图观察心脏结构及功能,酶联免疫吸附技术(ELISA)检测动脉血浆Ang(1-7)水平。实时荧光定量PCR检测心肌血管紧张素转换酶2(ACE2)及Ang(1-7)受体Mas mRNA表达,免疫印迹技术检测P-ERK1/2、Mas及ACE2蛋白水平。结果 (1)术后4、8、12、14周K组收缩压明显升高,药物灌胃后明显降低(P均<0.01);(2)术后第8、12、14周,K组大鼠舒张末期及收缩末期室间隔厚度、舒张末期及收缩末期左心室后壁厚度、左心室质量指数均明显增加,药物灌胃后明显改善(P均<0.01);(3)K组血清Ang(1-7)水平在8、12周时明显升高(P均<0.01),14周时恢复正常(P>0.05),与K组比,O组Ang(1-7)水平8周时降低,在12、14周时明显升高(P均<0.01);(4)K组ACE2及Mas基因及蛋白水平8周时均上调,12、14周时均下调,p-ERK1/2各时间段表达均升高(P均<0.01);与K组比较,O组两基因及蛋白水平8周时明显降低,在12、14周时明显升高,P-ERK1/2各时间段表达均降低(P均<0.01)。结论 2K1C法成功制作肾性高血压大鼠模型并导致明显左心室肥厚;奥美沙坦明显降低肾性高血压大鼠血压、改善左心室肥厚,抑制血清Ang(1-7)水平及组织Mas、ACE2基因与蛋白水平下调。其改善心肌肥厚作用与其作用于Ang(1-7)/Mas/ERK1/2信号通路有关。展开更多
Hepatic fibrosis is considered a common response to many chronic hepatic injuries. It is a multifunctional process that involves several cell types, cytokines, chemokines and growth factors leading to a disruption of ...Hepatic fibrosis is considered a common response to many chronic hepatic injuries. It is a multifunctional process that involves several cell types, cytokines, chemokines and growth factors leading to a disruption of homeostatic mechanisms that maintain the liver ecosystem. In spite of many studies regarding the development of fibrosis, the understanding of the pathogenesis remains obscure. The hepatic tissue remodeling process is highly complex, resulting from the balance between collagen degradation and synthesis. Among the many mediators that take part in this process, the components of the Renin angiotensin system （RAS） have progressively assumed an important role. Angiotensin （Ang） II acts as a profibrotic mediator and Ang-（1-7）, the newly recognized RAS component, appears to exert a counter-regulatory role in liver tissue. We briefly review the liver fibrosis process and current aspects of the RAS. This review also aims to discuss some experimental evidence regarding the participation of RAS mediators in the pathogenesis of liver fibrosis, focusing on the putative role of the ACE2-Ang-（1-7）- Mas receptor axis.展开更多
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 int...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.展开更多
文摘目的探究血管紧张素(1-7)[angiotensin-(1-7),Ang-(1-7)]及线粒体组装受体(mitochondrial assembly of receptor,MasR)在子宫内膜癌中的表达及相关性。方法选取河北北方学院附属第一医院2017年4月~2019年4月治疗的16例正常子宫内膜组织,32例子宫内膜不典型增生组织和78例手术切除的子宫内膜癌组织,共126例。使用酶联免疫吸附法(ELISA)检测Ang-(1-7),Western blot检测MasR在组织中的表达情况。结果三组组织中,正常子宫内膜组织内Ang-(1-7)(χ^(2)=11.506,P=0.000)和MasR(χ^(2)=8.619,P=0.002)阳性率最低,子宫内膜癌组阳性率最高,差异均具有统计学意义。与另外两组相比,子宫内膜癌组Ang-(1-7)和MasR表达显著增高。Ang-(1-7),MasR表达水平和子宫内膜癌肿瘤分期(t≥2.82,P=0.001)、转移(F=33.35和13.80,P=0.000)及分化程度(t≥2.82,P=0.029)均有相关性。结论Ang-(1-7)及MasR参与了子宫内膜癌新生血管的生成,其表达增高可促发癌细胞增长,可用于治疗及预后子宫内膜癌的新靶点。
文摘Hepatic fibrosis is considered a common response to many chronic hepatic injuries. It is a multifunctional process that involves several cell types, cytokines, chemokines and growth factors leading to a disruption of homeostatic mechanisms that maintain the liver ecosystem. In spite of many studies regarding the development of fibrosis, the understanding of the pathogenesis remains obscure. The hepatic tissue remodeling process is highly complex, resulting from the balance between collagen degradation and synthesis. Among the many mediators that take part in this process, the components of the Renin angiotensin system （RAS） have progressively assumed an important role. Angiotensin （Ang） II acts as a profibrotic mediator and Ang-（1-7）, the newly recognized RAS component, appears to exert a counter-regulatory role in liver tissue. We briefly review the liver fibrosis process and current aspects of the RAS. This review also aims to discuss some experimental evidence regarding the participation of RAS mediators in the pathogenesis of liver fibrosis, focusing on the putative role of the ACE2-Ang-（1-7）- Mas receptor axis.
基金Supported by Grant from the National Health and Medical Research Council of Australia
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.
