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The Study on the Injury of Liver in the Acute Cold Exposure and Its Possible Mechanisms

Author: WangJiYe
Tutor: XuMei；ChenJingYuan；ZhengGang
School: Fourth Military Medical University
Course: Human Movement Science
Keywords: Cold Exposure Rats PI3K-Akt-mTOR pathway ATP Mitosis Binucleate cells
CLC: R363
Type: Master's thesis
Year: 2010
Downloads: 31
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Abstract

The research background cold winter outdoor activities will be exposed to a low temperature environment. Personnel engaged in the operation of the low-temperature environment and participate in the special environment of the military activities of the officers and men are often exposed to the low-temperature environment. The low temperature environmental effects on the body and how to prevent low-temperature exposure-related disease has been a focus for researchers, is of great significance. Low temperature environment for its special military status and role of the mechanism of the human body damage, there is little relevant content publicly reported. At present, people of low-temperature environment for the study of the body's mechanism of injury, mostly restricted to long-term chronic exposure model, acute low temperature exposure model has yet to see the relevant reports. In winter cold areas in the north, the forces soldiers to perform field patrols and sentry duty task needs to be exposed in a cold environment, improper protective measures likely to result in acute frostbite. For acute cold injury is more concentrated in the surface of the skin and muscle tissue frostbite body organs affected in acute low temperature exposure and the role of yet to see the reports. Human exposure to low temperature environment, the need to mobilize the heat production to maintain body temperature. Although of muscle shivering production at this time hot dominant role, but the liver as glycogen in the body storage organs and resting heat production organ, may also be involved in the process of acute hypothermia and exposure to the body's stress. In the normal growth process of the rat and human liver can form a certain number of binucleated cells, binucleated cell formation may be associated with liver damage and proliferation ability. Lack of energy or other damage effect under the liver cell mitosis failed to form a dual-core cells. PI3K-Akt-mTOR pathway is an important survival signaling pathways involved in cell energy metabolism, proliferation, differentiation, growth and reproduction, and other important processes. Play a role in the process of low temperature exposure in a chronic model studies, but in acute low temperature exposure model and in the liver has not been elucidated. This study attempts to establish acute low temperature exposure model of acute low temperature exposure can cause liver pathophysiology, and explore the PI3K-Akt-mTOR pathway is involved in the response process and its regulatory mechanism in the process of acute low temperature exposure, in order to explore more low temperature exposure effect markers and prevention targets provide a theoretical basis. Research purposes in rats with acute low temperature exposure model to study acute hypothermia and exposure to the pathophysiology of the liver caused by rats, observed liver mitotic cells and dual-core changes in the number of cells in the process of low temperature exposure and changes in cellular energy levels. While observing changes PI3K-Akt-mTOR pathway and its relationship with liver pathophysiological changes. Whether through the use of pathway inhibitors to observe the changes in the relationship of the PI3K-Akt-mTOR pathway and liver cell energy levels and their participation in the liver cell mitosis and binucleated cell formation process. Research methods using low-temperature laboratory modules, the establishment of the model in rats with acute low temperature exposure: exposure to a temperature of -15 ° C, exposure time of 0.5 h, 1 h, 2 h and 4 h. Using the group method, rat liver injury and acute low temperature exposure dual-core cell formation was observed by HE staining. 3. Use of electron microscopy to observe the impact of acute low temperature exposure on rat liver ultrastructure. 4 using western blot method, the changes observed PI3K-Akt-mTOR pathway in acute low temperature exposure. Results from HE staining results can be found with the exposure time, the degree of injury of the rat liver gradually deepened. 0.5 h with mild hepatic cell edema in the low-temperature exposure, cells degeneration, edema, liver cells the mitotic increase and a large number of dual-core cells and a small number of apoptotic cells, can be found in the low temperature after 4 h of exposure. Electron microscopy results can be found in the low temperature exposure can lead to a decrease in liver glycogen 0.5 h, mitochondria mild swelling; cryogenic 4 h exposure can cause liver cell glycogen depletion, markedly swollen mitochondria, endoplasmic reticulum compression, wrapping in mitochondria around. Determination of liver cell ATP content found in the low-temperature exposure for 0.5 h, liver cell ATP content increased significantly, and with the exposure time and gradually reduced (p lt; 0.05). Western blot test results found the PI3K-Akt-mTOR pathway associated protein first and then decreased transient activation of Akt protein Ser-473 sites, Thr-308 sites; mTOR protein Ser-2448 sites, Ser-2481 sites and p70 S6K protein THR-389 loci 0.5 h, the degree of phosphorylation was significantly increased in the low temperature exposure, with the exposure time is gradually reduced. Determination of mitochondrial protein expression of Akt protein and mTOR protein expression in mitochondria in the cytoplasm trend. In addition, associated with the energy of the AMPK protein THR-172 loci with exposure time while the gradual increase in the extent of phosphorylation. 4. Further confirmed acute low temperature exposure can be induced rat liver silk separatist increase and dual-core cell formation increased use of immunohistochemical methods to count the rat liver dual-core cells, results found that low temperature exposed to 4 h, rat liver have mitotic cells The marked increase in the number of, and double the number of nucleated cells increased significantly (p lt; 0.05). By intraperitoneal injection of inhibitors wortmannin (of wortmannin) found that low-temperature exposure significantly decreased compared to 4 h ATP levels of rat liver cells with non-inhibitor treated, compared with room temperature control group was significantly higher (p lt ; 0.05). Rat liver, no significant change in percentage of cells in mitosis, binucleate cells increased significantly (p lt; 0.05). Conclusions 1. Acute low temperature can cause liver damage in rats exposed to 4 h, causing abnormal liver cell ATP levels increase induced resting period liver cells enter mitosis, and is accompanied by a large number of dual-core cell formation. 2. PI3K-Akt-mTOR pathway is involved in acute low temperature exposure on rat liver injury, involved in the low-temperature exposure the ATP production adjustment process and promote liver cell mitosis and dual-core cell formation.

The Study on the Injury of Liver in the Acute Cold Exposure and Its Possible Mechanisms

Abstract

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