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过氧化物酶体增生物激活受体γ(peroxisome proliferator-activated receptor gamma,PPAR-γ)激动剂主要包括噻唑烷二酮类(thiazolidinediones,TZDs)和非噻唑烷二酮类新型PPAR-γ激动剂。噻唑烷二酮类药物常用的有曲格列酮、吡咯列酮及罗格列酮。PPAR-γ激动剂的常见不良反应之一为水肿,并可加重或引致充血性心力衰竭。水肿发生率为3%~28.9%;PPAR-γ激动剂和其他口服降血糖药或胰岛素合用可增加水肿发生率。PPAR-γ引起水肿的机制涉及水钠潴留、血管扩张以及血管通透性增加等因素,特别是分布于远端肾小管和集合管的水、钠转运蛋白调节异常对水钠潴留的发生起重要作用。PPAR-γ激动剂引起的水肿一般较轻,停药后可消退。糖尿病合并中、重度充血性心力衰竭患者[NYHA(New York Heart Association)Ⅲ或Ⅳ级]避免用PPAR-γ激动剂,合并轻度充血性心力衰竭患者(NYHAI至Ⅱ级)应慎用,尽可能用最小剂量,必需时,剂量应逐渐增加,可联合应用利尿剂,并应严密监测患者体重和水肿的发生情况。预防治疗水肿的方法包括应用新的选择性PPAR-γ调节剂、蛋白激酶C-β或上皮细胞钠通道的特异性抑制剂及PPAR-γ拮抗剂。
Peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists mainly include thiazolidinediones (TZDs) and novel non-thiazolidinedione PPAR-γ agonists . Thiazolidinediones are commonly used troglitazone, pioglitazone and rosiglitazone. One of the common side effects of PPAR-gamma agonists is edema, which can aggravate or cause congestive heart failure. Edema rate of 3% to 28.9%; PPAR-γ agonists and other oral hypoglycemic agents or insulin can increase the incidence of edema. The mechanism of PPAR-γ-induced edema involves water and sodium retention, vasodilation and increased vascular permeability and other factors, especially in water distributed in the distal tubules and collecting duct, and dysregulation of sodium transporter plays an important role in the occurrence of Shuinazhuliu effect. Edema caused by PPAR-γ agonists is generally mild, subsided after withdrawal. Patients with diabetes mellitus and moderate to severe congestive heart failure [NYHA (New York Heart Association) class III or IV] should avoid caution and avoid using PPAR-gamma agonist in patients with mild congestive heart failure (NYHAI to grade II) May use the minimum dose, if necessary, the dose should be gradually increased, the diuretics can be combined, and should closely monitor the patient’s weight and edema occurred. Methods of prophylaxis and treatment of edema include the use of novel selective PPAR-γ modulators, specific inhibitors of protein kinase C-β or epithelial sodium channels, and PPAR-γ antagonists.