Mechanism of hydrogen-rich water alleviating radiation-induced cognitive impairment through PI3K/AKT/Caspase-9 pathway mediating anti-oxidation.

Explore the mechanism by which the antioxidant effect of hydrogen-rich water alleviates radiation-induced cognitive impairment based on the PI3K/AKT/Caspase-9 signaling pathway. Male SD rats were randomly divided into control group (Control group), simple irradiation (IR) group, high-dose hydrogen-rich water intervention (IR + HHRW) group, and low-dose hydrogen-rich water intervention (IR + LHRW) group. The irradiation dose was 20 Gy, and the whole brain was irradiated. The control group and IR group were given pure water (20 mL·kg^-1), and the IR + HHRW group and IR + LHRW group were given hydrogen-rich water (20 mL·kg^-1, 10 mL·kg^-1) for 30 days. Within 30 days after irradiation, the irradiated rats all had hair loss on the head, and the IR group showed the most obvious hair loss, and the IR + HHRW group had the mildest degree of hair loss. In the second week after irradiation, the irradiated rats showed a decrease in food intake and weight loss. During this period, the food intake and body weight loss of the rats in the IR + HHRW group were lower than those in the IR and IR + LHRW groups. At the third week after irradiation, the food intake and body weight of the rats in each group began to gradually recover, and the rats in the IR + HHRW group fastest recovered. Hematological tests showed that after irradiation, the BRC and HGB of the rats in the IR group decreased, and the levels of RBC and HGB in the IR + HHRW group tended to increase compared with the IR group. The results of the novel object recognition (NOR) experiment showed that compared with the IR group, the rats in the IR + HHRW group had a significantly higher preference index for new objects. The results of the Morris water maze test showed that compared with the IR group, the escape latency of the rats in the IR + LHRW group and the IR + HHRW group was shortened, among which, on the 5th day, the IR + HHRW group had a significant difference; on the 6th day, compared with the Control group, the time for the rats in the IR group to reach the platform for the first time was significantly longer, and the time for the rats in the IR + HHRW group to reach the original platform for the first time was significantly shorter than that of the IR group, and the times of crossing the platform and the time of staying in the quadrant of the original platform were both prolonged (p < 0.05). HE staining and TUNEL staining showed that the number of apoptotic hippocampal neurons in the IR group was significantly higher than that in the control group, and the number of apoptotic hippocampal neurons in the IR + HHRW group was less than that in the IR group. The detection of oxidative stress indicators in brain tissue showed that compared with the IR group, the levels of ROS, MDA and IL-6 in the IR + HHRW group were significantly lower; SOD and GSH were significantly higher. PCR results: Compared with the IR group, the expression levels of genes PI3K and AKT in the IR + HHRW group were significantly increased, and the expression levels of apoptosis factors Caspase-9 and Cytc were significantly decreased. Western-Blot results: Compared with IR group, IR + HHRW histone PI3K, pAKT expression was significantly increased, apoptosis factor Caspase-9 and Cytc protein expression was significantly decreased. Hydrogen-rich water can improve the radiation-induced cognitive impairment in rats induced by ionizing radiation through anti-inflammation, anti-oxidation, and regulation of PI3K/AKT/Caspase-9 pathway, and there is a certain dose-effect relationship.