Department of Pharmacology, Taipei Medical University, Taipei 114, Taiwan.
Eur J Pharmacol. 2013 Jan 15;699(1-3):67-73. doi: 10.1016/j.ejphar.2012.11.044. Epub 2012 Dec 5.
Heat stroke is a life-threatening illness characterized by an elevated core body temperature. Despite adequate lowering of the body temperature and support treatment of multiple organ-system function, heat stroke is often fatal. 3-(5'-Hydoxymethyl-2'-furyl)-1-benzyl-indazol (YC-1) been identified as an activator of soluble guanylate cyclase. To evaluate whether YC-1 protects multiple organ dysfunctions and improves survival during heat stroke and its mechanism. Male Sprague-Dawley rats untreated or treated with either YC-1 or quercetin (heat shock protein (Hsp) 70 inhibitor) were exposures to heat as a model of heat stroke. The mean arterial pressure (MAP), heart rate, rectal temperature (Tco), survival time, and plasma biochemical data, intracellular Hsp70 and heat shock factor-1 expression were measured. The value of MAP, heart rate and Tco of untreated heat stroke (HS) group were all significantly lower than that of normothermal (NT) group. Biochemical markers evidenced that liver and kidney injuries of HS group were significantly higher than that of NT groups. YC-1 (20mg/kg) pretreatment with heat stroke (YC-1+HS) group, the MAP and heart rate were return to normal, and the biochemical markers were all significantly recovered to normal. The survival time of HS group, NT group and YC-1+HS group were 21, 480, and 445 min, respectively. The expression of Hsp70 and HSF-1 in liver and renal of YC-1+HS group was significantly higher than that of HS group. All of the protective effects of YC-1 were all significantly suppressed when pretreated with quercetin (400mg/kg). Results indicate that YC-1 may improve survival due to induce Hsp70 overexpression.
热射病是一种危及生命的疾病，其特征是核心体温升高。尽管充分降低体温并支持治疗多个器官系统功能，但热射病通常是致命的。3-(5'-羟甲基-2'-呋喃基)-1-苄基-吲唑（YC-1）已被确定为可溶性鸟苷酸环化酶的激活剂。评估 YC-1 是否在热射病期间保护多个器官功能障碍并提高存活率及其机制。雄性 Sprague-Dawley 大鼠未经处理或用 YC-1 或槲皮素（热休克蛋白（Hsp）70 抑制剂）处理，然后暴露于热中作为热射病模型。测量平均动脉压（MAP）、心率、直肠温度（Tco）、存活时间和血浆生化数据、细胞内 Hsp70 和热休克因子-1 的表达。未经处理的热射病（HS）组的 MAP、心率和 Tco 值均明显低于正常体温（NT）组。生化标志物表明 HS 组的肝和肾损伤明显高于 NT 组。YC-1（20mg/kg）预处理的热射病（YC-1+HS）组，MAP 和心率恢复正常，生化标志物均明显恢复正常。HS 组、NT 组和 YC-1+HS 组的存活时间分别为 21、480 和 445 分钟。YC-1+HS 组肝和肾中的 Hsp70 和 HSF-1 表达明显高于 HS 组。当用槲皮素（400mg/kg）预处理时，YC-1 的所有保护作用均明显受到抑制。结果表明，YC-1 可能通过诱导 Hsp70 过表达来提高存活率。
