Investigation of organ injury mechanism in experimental heatstroke

• Main Authors: Tsung-Ta Liu, 劉宗達
• Other Authors: Jia-Yi Wang
• Format: Others
• Language: zh-TW
• Published: 2011
• Online Access: http://ndltd.ncl.edu.tw/handle/85102556651803295442

博士 === 國防醫學院 === 生命科學研究所 === 99 === The phenomenon of global warming become more and more serious. Scientists have claimed that the global surface temperature could increase about 1.5-4℃. One of the consequences of global warming is an increase in the frequency and intensity of heat waves. Exposure to extremely hot environment (such as fire fighter, miner or military training) or hot weather can induce heat-related diseases such as heat cramps, heat exhaustion and heatstroke. Heatstroke (HS) is defined clinically as a condition when core body temperature rises above 40℃(hyperthermia) and is accompanied with the central nervous system abnormalities and multi-organ dysfunction. The mortality of HS ranges from 10-70%. HS complications include brain damage, respiratory abnormality, cardiovascular collapse, and renal failure. Although the cellular mechanism of heat stress-induced cell death has been thought to play an important role, the mechanism of HS in metabolic and pathologic changes is not clearly understood. In this thesis, we first found that HS induces autophagy in cerebral cortex against neurodegeneration as a protection mechanism. We found neuronal shrinkage and pyknosis of the nucleus in cerebral cortex. Both LC3II and beclin-1 protein levels were increased in a time-dependent manner in response to HS. Pharmacological manipulation of autophagy with its inhibitor, 3-MA, reduced the expression of LC3II and beclin-1 proteins. In addition, staining with an autophagososome marker monodansylcadaverine (MDC), was consistent with autophagy-related protein expression pattern. Importantly, staining with the fluorescent dye Fluoro-Jade B (FJB) for degenerating neuron, we found that pretreatment with 3-MA in HS rats increased neuronal degeneration in cortical tissue. Second, we also found that HS induces heme oxygenase-1 (HO-1) in lung tissue against the damage as a protection mechanism. We found that acute HS induced lung injury evidenced by congested and thickened lung septum. Both protein and mRNA levels of HO-1 increase in a time-dependent manner in response to HS. Pharmacological manipulation of HO-1 with its inhibitor, SnPP, aggravates the damage of lung tissue. Furthermore, we have demonstrated HO-1 expression in the lung alveolar type II epithelium cells. Finally, we found that HS induced the cytokines which were including IL-1 β, IL-18, IL-10, IL-6, TNFα, GRO-KC, MCP-1 and Leptin.