Chinese scientists reveal the death mechanism of heat stroke

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Every summer, there are always a few people suffering from heat stroke, and heat stroke is a severe heat stroke. According to U.S. epidemiological data, once heat stroke induces heat exhaustion, the mortality rate can reach 63.2%. With record-breaking heatwaves causing many heat-related deaths worldwide over the past 20 years, heat stroke could become a major threat to human life as the global climate continues to warm.

In the past, scientists believed that heat stroke was a physical injury process. High heat produced cytotoxic effects. When the temperature in the human body continued to rise to a certain threshold, it would directly cause irreversible damage to cells, and then trigger the function of multiple organs in the body. exhaustion. Despite aggressive clinical cooling and organ support, the mortality rate of heat stroke remains high.

Recently, researchers from Central South University conducted a detailed study of heat stroke and found that heat stroke is caused by excessive programmed cell death induced by hyperthermia through Z-DNA binding protein-1 (ZBP1), which in turn leads to life-threatening disseminated blood vessels. Internal coagulation (DIC) and multiple organ damage.

Specifically, cell death is an important physiological phenomenon in biological life processes. Based on different classification criteria, it can be divided into programmed death and non-programmed death. Programmed death is the normal apoptosis of cells, which is very important for biological growth, development and normal activities, and excessive programmed cell death will lead to physical failure.

To study the role of programmed cell death in heat stress, the researchers used four gene knockout or mutant mice, RIPK3 gene deletion (Ripk3-/-) mice, MLKL gene deletion (Mlkl-/-) mice ) mice, MLKL and caspase 8 gene deletion (Mlkl-/-Casp8-/-) mice, RIPK3 kinase domain mutant (Ripk3Δ/Δ) mice.

It was found that hyperthermia induces multiple programmed cell death through the RIPK3 pathway rather than the HMGB1-caspase-11 pathway, which in turn leads to DIC and multiple organ damage . In addition, hyperthermia induces the phosphorylation of RIPK3 and MLKL in organs such as liver, lung and intestine, as well as the cleavage of apoptosis-related proteins such as caspase-8. Knockout of RIPK3 gene can indeed prevent hyperthermia-induced multiple organ damage and die.

Subsequently, the researchers used ZBP1 gene-deficient (Zbp1-/-) mice, and placed Zbp1-/- mice and their control wild-type mice in a high temperature and high humidity environment to induce heat stress. The results suggest that heat stress mediates RIPK3 activation through ZBP1, thereby promoting the development of heat stress pathological features.

In the future, the research may reduce heat stroke-related casualties.