背景:全球脓毒症休克的发病率和死亡率居高不下,尽管去甲肾上腺素可以增加危重病人的血压,但对额外治疗的需求未得到满足。方法:特利加压素与去甲肾上腺素治疗感染性休克的多中心随机对照试验来解决这个问题。结果:将617例患者随机分配到特利加压素(n = 312)或去甲肾上腺素输注(n = 305)联合标准治疗组,其中包括开放标签血管加压药。对主要终点,即亚组28天死亡率(特利加压素n = 260;去甲肾上腺素n = 266)进行了先验改良的意向治疗初步分析。28天死亡率无差异(特利加压素 = 40%,去甲肾上腺素 = 38%,p NS)。选定的次要终点,如存活天数和无血管加压药天数以及脓毒症器官衰竭评估(SOFA)评分的变化,组间没有差异。然而,特利加压素组的不良事件比去甲肾上腺素组更严重(30% vs. 12%, P Background: The incidence and mortality of septic shock remain high globally, and although norepinephrine can increase blood pressure in critically ill patients, there is an unmet need for additional treatment. Methods: A multicenter randomized controlled trial of teripressin versus norepinephrine for septic shock was conducted to address this issue. Results: 617 patients were randomly assigned to teripressin (n = 312) or norepinephrine infusion (n = 305) in combination with standard care, which included open-label vasopressors. For the primary endpoint, the subgroup 28-day mortality (teripressin n = 260;Norepinephrine n = 266) performed a preliminary analysis of intention-to-treat with a priori modification. There was no difference in mortality at 28 days (teripressin = 40%, norepinephrine = 38%, pNS). Selected secondary endpoints, such as days of survival and vasopressor free days and changes in the Sepsis Organ Failure Assessment (SOFA) score, did not differ between groups. However, adverse events were more severe in the teripressin group than in the norepinephrine group (30% vs. 12%, P < 0.01). Conclusions: There was no difference
精氨酸加压素(Arginine Vasopressin, AVP),又称抗利尿激素(Antidiuretic Hormone, ADH),是一种由下丘脑合成的环状九肽神经激素,在机体水盐平衡和血压稳态调节中发挥核心调控作用。AVP通过特异性结合G蛋白偶联受体(G Protein-Coupled Receptor, GPCR)家族成员V1受体(Vasopressin type 1 receptor, V1R)和V2受体(Vasopressin type 2 receptor, V2R)介导其生理功能:V1R主要分布于血管平滑肌,参与调控血管张力及血小板活化;V2R则高表达于肾脏集合管和远端肾小管,通过调节水通道蛋白2 (Aquaporin-2, AQP2)的膜转运介导水的重吸收。近年来,随着冷冻电子显微镜(Cryogenic Electron Microscopy, Cryo-EM)等结构生物学技术的突破,研究人员成功解析了AVP受体复合物的高分辨率三维结构,为阐明其配体识别机制和信号转导途径提供了重要的结构基础。这些研究成果不仅深化了对AVP信号通路的分子机制理解,也为基于结构的精准药物设计提供了新思路。基于V1R和V2R结构特征开发的高选择性配体有望为高血压、尿崩症等疾病的治疗提供更安全有效的治疗方案。Arginine vasopressin (AVP), also known as antidiuretic hormone (ADH), is a cyclic nonapeptide neurohormone synthesized in the hypothalamus, playing a critical role in maintaining water-electrolyte balance and blood pressure homeostasis. AVP mediates its effects through specific binding to G protein-coupled receptors (GPCRs), primarily V1R and V2R. V1R is predominantly expressed in vascular smooth muscle, where it regulates vascular tone and platelet activation, V2R is highly expressed in the renal collecting ducts and distal nephron, where V2R orchestrates water reabsorption by modulating the membrane trafficking of aquaporin-2 (AQP2). In recent years, with the breakthroughs in structural biology techniques such as Cryogenic Electron Microscopy (Cryo-EM), researchers have successfully determined the high-resolution three-dimensional structure of the arginine va
