Study of Multi-Organ Damage in Heatstroke-Induced Rats

The average global annual temperature has risen from 14.5°C in 1886 to15.8°C in 2008. The phenomenon of global warming become more and more serious. 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. The World Health Organization (WHO) estimates that the global warming due to anthropogenic climate change of the past 30 years already claim over 150000 lives annually. 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. HS is also caused by intensive exercises or strenuous physical activities in high-temperature environments. The mortality of HS ranges from 10-50%. 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 a important role, the mechanism of HS in metabolic and pathologic changes is not clearly understood. In this proposal, we will investigate HS-induced tissue damage in rats with the following specific aims: (2012/10/01~2013/09/30) 1. To establish a rat model of heatstroke A - To identify the degree of tissue damage in various organs (kidney, brain, lung, liver etc.) in HS rat B - To investigate the time dependently mechanism of injury (apoptosis or autophagy) are involved in the mechanism of injury in various organs (2013/10/01~2014/09/30) 2. To clarify the mechanism of injury in each organs A - To observe the severity of injury by administrating different inhibitors for each injury mechanism B - To identify the up/down stream molecules/signaling correlated with the expression of specific proteins (2014/10/01~2015/09/30) 3. To explore potential drugs preventing or alleviating the injury in tissues A - To investigate the protection effects of the drug against HS-induced injury in rat after HS B - To investigate the possible interaction between the drug and genes