程新刘宝玲王海滨金壮张杰林CrumpackerClyde人刘宝玲王海滨金壮张杰林CrumpackerClyde巨细胞病毒临床分离株感染血管内皮细胞伴肾素基因表达

目的探讨巨细胞病毒（Cytomegalovirus,CMV）是否感染血管内皮细胞伴肾素表达。方法（1）用10^7pfu（空斑形成单位）／mlCMV临床分离株BI-5和实验室型CMVAD169分别与10^6腹主动脉内皮细胞和人脐静脉内皮细胞共同孵育,在23小时后、第3天、第7天、第10天和第14天分别收集培养上清200μl,第14天用PBS缓冲液洗细胞3次,收获细胞。每组实验均设培养液代替病毒液的无感染对照;（2）COBAS定量PCR检测培养上清中CMVDNA拷贝数;（3）PCR检测感染细胞中CMVpol基因;（4）RT—PCR、RealtimeRT—PCR和Westernblot检测肾素在感染细胞内的表达。结果（1）BI-5和AD169感染静脉和动脉细胞后,其形态学变化相似,无细胞裂解病理效应;（2）ADl69感染细胞不同时间培养上清中CMVDNA拷贝数无明显增加,BI-5呈增殖趋势;（3）BI-5感染动脉细胞CMVDNA拷贝数和肾素表达量均大于静脉细胞。结论临床分离株CMV以非裂解形式在血管内皮细胞持续存在并诱导肾素基因表达,血管内皮细胞分泌肾素可能是CMV感染引起心血管疾病的新机制。     

原发性高血压与血浆肾素活性及血管紧张素原遗传关系研究

目的：分析血浆肾素活性（ＰＲＡ）、血浆血管紧张素原（ＡＯ）浓度与原发性高血压的关系。方法：在一个原发性高血压家系中随机抽取原发性高血压患者３１例（原发性高血压组）、正常血压者２５例（家系对照组），在６个正常对照家系中随机抽取２１例（正常对照组），测定ＰＲＡ、血浆ＡＯ及其它代谢因素。结果：调整年龄、性别、体重指数后原发性高血压家系内无论有无原发性高血压患者，ＰＲＡ均显著低于正常对照组（Ｐ＜００５）；原发性高血压组血浆ＡＯ显著高于正常对照组（Ｐ＜００５），高密度脂蛋白胆固醇显著低于正常对照组（Ｐ＜００５）。结论：具有原发性高血压遗传因素者无论是否患有原发性高血压均有显著的ＰＲＡ、血浆ＡＯ异常和其它代谢紊乱，这些异常可能在超重和原发性高血压发生前即已存在     

阻断肾内肾素-血管紧张素系统对转化生长因子β1mRNA及细胞外基质表达的作用

目的探讨苯那普利延缓肾脏疾病进展的可能作用机制。方法采用实验性肾小球硬化模型,治疗组给苯那普利（４ｍｇ·ｋｇ－１·ｄ－１）。用比色法和放免法分别测定肾内血管紧张素转换酶（ＡＣＥ）活性和血管紧张素Ⅱ（ＡｎｇⅡ）含量,免疫组化检测肾组织转化生长因子β１（ＴＧＦβ１）和细胞外基质（ＥＣＭ）,原位杂交观察ＴＧＦβ１ｍＲＮＡ表达。结果治疗组肾内ＡＣＥ活性和ＡｎｇⅡ与非治疗组比较,受到明显抑制（Ｐ＜０．０１）。治疗组肾小球和肾小管区ＴＧＦβ１ｍＲＮＡ表达量显著低于非治疗组（Ｐ＜００１）。同时,ＥＣＭ在肾小球内沉积也较非治疗组显著减少（Ｐ＜０．０１）。结论苯那普利通过阻断肾内肾素血管紧张素系统,在下调ＴＧＦβ１表达和ＥＣＭ积聚中起重要作用。     

组织中肾素—血管紧张素—醛固酮系统的实验研究

为了解组织中肾素－血管紧张素－醛固酮系统情况，用离体肾灌注、高效液相分析、放免检测、肾素基因保留时间（ＲＴ）－ＰＣＲ检测首次证明肾脏也可合成醛固酮。双肾切除３０小时使血浆肾素活性消失之后，用ＲＴ－ＰＣＲ技术表明血管仍可表达肾素ｍＲＮＡ，从而说明血管不同于心脏、具有独立的肾素合成能力。血管紧张素转换酶抑制剂培哚普利，不仅可抑制血管局部血管紧张素Ⅱ的生成，还可抑制血管醛固酮的合成，从而进一步解释培哚普利逆转血管重构的作用机理。     

下丘脑室旁核肾素-血管紧张素系统对心衰时炎性细胞因子及交感神经的影响

目的研究心衰时下丘脑室旁核中肾素一血管紧张素系统对炎性细胞因子表达水平的影响,及在外周交感神经过度兴奋和心衰发生发展中发挥的作用。方法雄性sD大鼠28只,体重（250±20）g,结扎冠状动脉左前降支制备心衰模型。给药组通过双侧室旁核给予血管紧张素转化酶抑制剂依那普利（EPI,10μg／rrd）4周,对照组给予人工脑脊液。检测全心体重比、肺体重比、血浆中去甲肾上腺素水平、血浆中自介素-1β含量。结果心衰组大鼠全心体重比为（7．2±0．6）,肺体重比为（11．6±0．9）,较假手术组升高（P〈0．05）,血浆中去甲肾上腺素水平为（251．7±22．4）pg／ml,较假手术组升高（P〈O．05）,血浆中白介素-1β表达水平为（112．3±10．5）pg／ml,较假手术组升高（P〈0．05）。给药组全心体重比为（5．4±0．5）,肺体重比为（7．8±0．8）,较心衰组降低（P〈0．05）,血浆中去甲肾上腺素水平为（209．6±20．5）pg／ml,较心衰组降低（P〈0．05）,血浆中白介素-18含量为（84．7±7．6）pg／ml,较心衰组降低（P〈0．05）。结论心衰时下丘脑室旁核中肾素-血管紧张素系统促进炎性细胞因子表达,激活外周交感神经,促进心衰的发生发展。     

Effect of Renin‐Angiotensin System Inhibitor on Residual Glomerular Filtration Rate in Hemodialysis Patients

Residual renal function preservation in patients with renal failure has been shown to be related to better outcomes not only in the pre‐dialysis phase but also after hemodialysis initiation. However, the effect of factors such as antihypertensive agents on residual renal function preservation has not been investigated adequately in prevalent hemodialysis patients. This study examined factors related to the rate of residual renal function preservation in 1‐year hemodialysis patients who had residual renal function. We enrolled 191 consecutive maintenance hemodialysis patients who underwent hemodialysis for 1 year and maintained a urine output of more than 200 mL/day, to assess residual renal function loss. The rate of residual renal function loss was 19.9%. Multivariate analysis using residual renal function as the dependent variable revealed significant independent relationships with renin‐angiotensin system inhibitor use (hazard ratio, 0.438; P = 0.027), history of cardiovascular disease (hazard ratio, 2.475; P = 0.024), and rate of weight gain between dialysis sessions (hazard ratio, 1.348; P = 0.013). No relationship was observed with calcium channel blocker use. Renin‐angiotensin system inhibitor use, rate of body weight gain between dialysis sessions, and cardiovascular diseases are independently associated with residual renal function preservation in patients with residual renal function after 1 year of hemodialysis. A further intervention study is required to investigate whether treatment with renin‐angiotensin system inhibitors and suppression of body weight gain preserves residual renal function for a longer time in hemodialysis patients.     

雷米普利和氯沙坦对高胆固醇血症大鼠早期动脉粥样硬化形成的影响

目的 :观察血管紧张素转换酶抑制剂 (ACEI)雷米普利和血管紧张素Ⅱ (AngⅡ ) 1型受体拮抗剂氯沙坦对高胆固醇血症大鼠早期动脉粥样硬化 (AS)形成的影响 ,探讨肾素 血管紧张素系统 (RAS)致早期AS的机制。方法 :4 0只雄性SD大鼠随机分为正常对照 (NC)组 ,高脂 (HL)组 ,雷米普利 (Ram )组和氯沙坦 (Los)组。每组 10只 ,10周后比色法测血清一氧化氮 (NO)、丙二醛 (MDA)水平及超氧化物歧化酶 (SOD)活力 ,酶法测血胆固醇浓度 ;用免疫组化法检测主动脉血管壁增殖细胞核抗原 (PCNA)和核转录因子 (NFκB)及细胞间粘附分子 1(I CAM 1)表达水平 ;透射电镜观察主动脉形态结构 ,苏木精 伊红染色高倍视野下计数浸润于内膜的单核细胞数。结果 :Ram组和Los组血清NO浓度和SOD活力显著高于HL组 (P <0 .0 1) ,而MDA水平低于HL组 (P <0 .0 1) ,NFκB活化及ICAM 1表达水平 ,PCNA阳性细胞数和浸润的单核细胞数明显少于HL组 (P <0 .0 1) ,但这三组间血胆固醇浓度差异无显著性意义。Ram组和Los组主动脉内皮损伤明显轻于HL组。结论 :Ram和Los能缓解自由基损伤 ,抑制高胆固醇血症大鼠ICAM 1表达和单核细胞浸润 ,防止早期AS形成。     

依那普利、厄贝沙坦及血管紧张素-（1—7）对快速心房起搏犬肾素-血管紧张素系统的影响

目的观察快速心房起搏模型犬血管紧张素转换酶2（ACE2）和血管紧张素III型受体（ATlR）mRNA表达的变化,以及应用依那普利、厄贝沙坦及血管紧张素（Ang）-（1-7）对其影响。方法健康成年杂种犬30只,分为5组：假手术组（S组）,心房起搏对照组（C组）,心房起搏＋依那普利组（EN组）,心房起搏＋厄贝沙坦组（IB组）,心房起搏＋血管紧张素-（1-7）组（A组）,每组6只。S组植入起搏器,但不行起搏刺激及药物干预。C组植入起搏器并起搏,但无药物干预。EN组及IB组分别于起搏开始前3d开始给予口服依那普利2mg·kg^-1·d^-1或厄贝沙坦60mg·kg^-1·d^-1。A组给予Ang-（1-7）6μg·kg^-1·h^-1持续静脉泵人。各组犬经500次／min快速心房起搏2周后,采集右心房肌标本,逆转录聚合酶链式反应（RT—PCR）检测心房肌组织中ACE2和ATlRmRNA表达。结果心房起搏组较假手术组ACE2表达降低,ATlR表达明显升高,应用依那普利、厄贝沙坦和Ang－（1-7）可使ACE2表达增加和ATIR水平下调。结论快速心房起搏2周可诱发心脏局部肾素－血管紧张素（RAS）系统的活化,依那普利、厄贝沙坦和Ang－（1-7）可抑制起搏后的RAS系统激活,降低心房颤动的易感性。Ang－（1-7）的心脏保护作用可能通过下调ATIR和上调ACE2来介导。     

Renin and cardiovascular disease: Worn-out path, or new direction

Inhibition of the renin angiotensin system has beneficial effects in cardiovascular prevention and treatment. The advent of orally active direct renin inhibitors adds a novel approach to antagonism of the renin-angiotensin system.Inhibition of the first and rate-limiting step of the renin angiotensin cascade offers theoretical advantages over downstream blockade.However,the recent discovery of the(pro)renin receptor which binds both renin and prorenin,and which can not only augment catalytic activity of both renin and prorenin in converting angiotensinogen to angiotensinⅠ,but also signal intracellularly via various pathways to modulate gene expression,adds a significant level of complexity to the field.In this review,we will examine the basic and clinical data on renin and its inhibition in the context of cardiovascular pathophysiology.     

Role of renin-angiotensin system in liver diseases: an outline on the potential therapeutic points of intervention

Introduction: The current review aimed to outline the functions of the renin angiotensin system (RAS) in the context of the oxidative stress-associated liver disease.

Areas covered: Angiotensin II (Ang II) as the major effector peptide of the RAS is a pro-oxidant and fibrogenic cytokine. Mechanistically, NADPH oxidase (NOX) is a multicomponent enzyme complex that is able to generate reactive oxygen species (ROS) as a downstream signaling pathway of Ang II which is expressed in liver. Ang II has a detrimental role in the pathogenesis of chronic liver disease through possessing pro-oxidant, fibrogenic, and pro-inflammatory impact in the liver. The alternative axis (ACE2/Ang(1-7)/mas) of the RAS serves as an anti-inflammatory, antioxidant and anti-fibrotic component of the RAS.

Expert commentary: In summary, the use of alternative axis inhibitors accompanying with ACE2/ Ang(1-7)/mas axis activation is a promising new strategy serving as a novel therapeutic option to prevent and treat chronic liver diseases.