目的:热预处理和热休克蛋白(HSP)合成对随后的应激源的应用引起的细胞损伤的发展具有显着的细胞保护作用,这取决于压力源之间的时间段。我们旨在确定热应激暴露和事先应用糖尿病链脲佐菌素(STZ)后最有效的恢复时间(6小时或24小时),以减轻糖尿病引起的碳水化合物和氧化代谢紊乱。
方法:实验动物(Wistar大鼠)在41±1°C下暴露于急性热应激45分钟,然后在室温下进行6小时或24小时的恢复时间,然后处死或施用STZ。
结果:我们的发现表明,急性热应激与6小时或24小时恢复期导致肝热休克蛋白70(HSP70)水平显着升高(24小时后更是如此)。糖原分解和稳定的血糖,随后糖酵解和糖异生活性降低(24小时后)(葡萄糖-6-磷酸酶,果糖-1,6-双磷酸酶);刺激抗氧化活性(谷胱甘肽过氧化物酶,谷胱甘肽还原酶)(6小时后);并降低谷胱甘肽和过氧化氢酶活性(24小时后)。在STZ诱导的糖尿病之前进行热预处理(6小时和24小时恢复期)会增加HSP70水平并导致血清葡萄糖水平降低,更高的糖原和葡萄糖-6-磷酸水平,与未经处理的STZ动物相比,降低了葡萄糖-6-磷酸酶水平和糖原磷酸化酶和己糖激酶水平,但也提高了谷胱甘肽还原酶和谷胱甘肽过氧化物酶的活性。
结论:根据我们的发现,1型糖尿病大鼠的热预处理和HSP70诱导减弱STZ诱导的肝脏碳水化合物代谢和氧化状态的代谢改变。这些变化在急性热应激后24小时恢复时更为明显,基于这个时间框架内最明显的HSP70积累。
OBJECTIVE: Heat preconditioning and heat-shock protein (HSP) synthesis have significant cytoprotective effects against the development of cellular injury caused by the application of a subsequent stressor, which were found to depend on the time period between the stressors. We aimed to determine the most efficient recovery time (6 h or 24 h) following heat-stress exposure and prior application of diabetic streptozotocin (STZ) on the moderation of carbohydrate and oxidative metabolic disturbances caused by diabetes.
METHODS: Experiment animals (Wistar rats) were exposed to acute heat stress at 41±1°C for 45 min, followed by 6-h or 24-h recovery times at room temperature before sacrifice or STZ administration.
RESULTS: Our findings indicate that acute heat stress with 6-h or 24-h recovery periods results in a significant rise in the hepatic heat-shock protein 70 (HSP70) levels (even more so after 24 h), glycogen breakdown and stable glycemia, followed by reduced glycolytic and gluconeogenic activity (after 24 h) (glucose-6-phosphatase, fructose-1,6-bisphosphatase); stimulates antioxidative activity (glutathione peroxidase, glutathione reductase) (after 6 h); and decreases glutathione and catalase activity (after 24 h). Heat preconditioning (with 6-h and 24-h recovery periods) prior to STZ-induced diabetes increases HSP70 levels and causes lower serum glucose levels, higher glycogen and glucose-6-phosphate levels, lower glucose-6-phosphatase levels and glycogen phosphorylase and hexokinase levels but also elevates glutathione reductase and glutathione peroxidase activity compared to untreated STZ animals.
CONCLUSIONS: Based on our findings, heat preconditioning and HSP70 induction in rats with type 1 diabetes attenuates STZ-induced metabolic alterations in hepatic carbohydrate metabolism and oxidative states. These changes are more evident at 24 h recovery post-acute heat stress, based on the most evident accumulation of HSP70 in this time frame.