Cobalt Chloride Protects Against Intestinal Irradiation-Induced Injury by Activating the HIF-2α

The evolving geopolitical landscape has heightened the probability of nuclear incidents, including accidental release or deliberate detonation, which can cause acute, life-threatening radiation injury to large populations. High-dose ionizing radiation (IR) is highly likely to cause radiation injury to the intestines and lead to intestinal radiation sickness. This study systematically explored the protective effect of cobalt chloride (CoCl₂) on intestinal radiation injury and its preliminary mechanism from multiple levels, including cells, intestinal tissues, intestinal organoids, and live mice. The results showed that CoCl₂ pretreatment could significantly enhance the radiation tolerance of mice, not only greatly improving the survival rate and multiple indicators such as intestinal injury score, but also maintaining the integrity of the small intestinal epithelial villi structure. At the same time, it promotes the proliferation and differentiation of intestinal organoids, inhibits the apoptosis of intestinal epithelial cells, and enhances the expression of barrier protection genes, thereby enhancing the intestinal resistance to radiation injury. Mechanism studies have shown that CoCl₂ can up-regulate the expression of hypoxia-inducible factor-2 α (HIF-2α) via hypoxia-mimetic action and activate downstream signaling pathways related to cell proliferation, anti-apoptosis, and angiogenesis. This study initially clarified the mechanism by which CoCl₂ protects the intestinal tract from radiation injury, providing a scientific basis and strategic support for the development of new radiation protection targets. Its in-depth research and application transformation are expected to play an important role in the future field of nuclear radiation protection.