糖尿病局部RAS激活及ARB治疗优势巡讲PPT课件.ppt

* * Zhang SL等在大鼠中进行的一项研究显示，与低水平葡萄糖（5mM）相比，高水平的葡萄糖（15-25mM）可显著增加大鼠近段肾小管细胞中血管紧张素原（IR-rANG）的表达。另一项国外研究亦显示，糖代谢异常产物（AGE）可使肾脏RAS各成分表达增加。提示葡萄糖代谢障本身就可以兴奋肾内RASS，引起高血压、肾小球硬化、蛋白尿、心血管病变等一系列病理生理改变，进而在糖尿病肾病的发病中起着重要作用。 * * * * 无论是循环RAS还是局部RAS，血管紧张素II兴奋，会直接引起血流动力学的变化，肾小球内压增高，肾小球毛细血管通透性增加，引起蛋白尿，并刺激炎症因子和血管活性基因，最后导致肾脏的纤维化 肾病时局部RAS激活的示意图 * 试验设计较复杂，只是想提供一个肾病时局部RAS活性高于循环RAS活性的试验证据，21张的内容与此类似，若觉得讲不清楚，可以去掉。若想讲的非常仔细，费时又偏离主题 * * * * Ang I and Ang II levels in renal interstitial fluid, plasma, and kidneys in which microdialysis probes were implanted in anesthetized rats (n=7). Renal interstitial concentrations of Ang I and Ang II were calculated based on equilibrium rates determined in vitro. * 蛋白尿形成会刺激炎症和血管活性基因，导致成纤维细胞增殖，间质炎症反应，合成细胞外基质增加最后导致肾疤痕化，导致肾脏的损害 * * Angiotensin II is the main effector hormone of the renin–angiotensin system. Angiotensin II is derived from angiotensinogen in the circulation via the sequential actions of renin and angiotensin-converting enzyme (ACE) and in tissues by renin and ACE as well as several other enzymes, including chymase and cathepsin G. Angiotensin II produces biologic effects that are important in cardiovascular pathophysiology as a result of binding to and activating the angiotensin type 1 (AT1) receptor. Currently available angiotehnsin II receptor blockers (ARBs) block this interaction, and thereby prevent these angiotensin II effects. Angiotensin II also binds to the angiotensin type 2 (AT2) receptor to produce effects that balance those elicited via the AT1 receptor. The ARBs do not block the interaction of angiotensin II with the AT2 receptor. * 而ARB可以降低肾脏的肾小球内压，同时阻断RAS的兴奋，从血流动力学及非血流动力学两方面来控制高血压，减少蛋白尿，从而延缓肾脏疾病的进展 * LIFE研究：氯沙坦干预高血压患者生存研究。 研究目的：比较患者血压对药物的反应，并在以下两组患者：即接受以氯沙坦为基础的抗高血压药物方案、或以阿替洛尔为基础的方案的患者间自基线起比较药物的抗高血压疗效。 试验设计：整个LIFE研究共纳入9193例55-80岁原发性高血压合并左室肥厚的患者，分为两大对照组别：以氯沙坦为基础的抗高血压方案组、以阿替洛尔为基础的方案组；并分为四个阶段：第一阶段2996例患者按约1:1比例随机分配单用氯沙坦50mg qd pp(n=1508)或阿替洛尔50mg qd po(n=1488)并比较两者降压强度，疗程共2月；后三阶段分别以不同药物加入两方案，联合治疗并行比较。本页PPT中仅涉及第一阶段实验成果。 主要终点：死亡、心肌梗死或