Studies On Mechanisms Of Intermittent Cold Exposure Increasing The Body’s Resistance To Cold

BackgroundCold is a common environmental exposure factor. When exposed to thecold environment for a long time, or with improper protective measures, thebody may be damaged, resulting in poor working capacity, cold injury, or evendeathTherefore, it’s of great importance to study the mechanisms of cold injury,and to explore appropriate protective measures to maintain people’s workingcapability in cold environment.Previous studies in our laboratory have found that PI3K-Akt pathway isinvolved in the hepatic energy metabolism under acute cold exposure; However,its mechanisms are still unclear. In this study, we employed SD rats toinvestigate the mechanisms of acute cold exposure-induced liver damage, and the protective effects of cold-adaption against the gamages of liver structure andfunction. The fundings in this study will be helpful to the further clarify themechanism of acute cold exposure-induced liver damage and to find neweffective measures to improve the body’stolerance to cold.AimsTo investigate the protective effects of cold adaption against theultrastructural and functional damages of liver under acute cold exposure and itspossible mechanisms.Methods1. Establishment of the acute cold exposure animal model and thecold-adaption animal model.2. Apoptotic cells in the liver following acute cold epsoure were stained byTUNEL. Liver cell mitochondria were obtained by a mitochondria isolationkit, and followed by the determineation of mitochondrial potential by JC-1method.3. The ultrastructure of liver cells was observed by a transmission electronicmicroscope (TEM).4. Western blot was performed to determine the levels of mitochondrial fusionproteins, caspase-3, and the phosphoralated Akt and ERK following the coldexpsure.Results1. The acute cold expsoure resulted in a significantly decreased coretemperature as well as the increased levels of glutamic-pyruvic transaminaseand glutamic-oxaloacetic transaminase.2. The number of apoptotic cells significantly increased following the acute cold expsoure. The activaty of caspase-3increased at the same time.3. The phosphoralated Akt level in liver cells is increased transiently followingthe acute cold exposure, and reduced after1hour timepoint. Cold adaptationcan maintain the phosphoralated Akt level in the liver tissue under coldexposure. Following the acute cold exposure for4h, the number ofapoptotic cells significant increased in the liver of non-adapted rats, but notin the cold-adapted rats, as compared to the controls. Cold adaption alsoproteced the liver cells against the acute cold exposure-induced activation ofcaspase3.4. Electron microscope examination revealed ultrastructural changes of the ratliver cells, such as abnormal shape of mitochondria, and exhasted glycogen,following the acute cold exposure. Cold adaption protected the rats againstthe acute cold exposure-induced damages of the mitochondrialultrastructure.5. The core temperature of the cold adapted rats decreased less than that of thenon-adapted rats, accompanying with less apoptotic cells, higher ERK andAkt phosphoralation, and higher mitochondrial fusion proteins levels in theliver.Conclusions1. The-15℃,4h cold exposure resulted in damaged ultrastructure andfunctions of the rat liver, as shown by increased cell apoptosis, abnormalmitochondria, and decrease ATP production.2. Cold adaptation can improve the body’s cold tolerance, probably byimproving the mitochondrial function and inhibit apoptosis in liver cells.