Abstract:
Objective To investigate the therapeutic effect of sitagliptin on hematopoietic system injury in mice after 7 Gy γ-ray irradiation.
Methods Fifteen C57BL/6 mice were randomly divided into a control group, an irradiation group, and a sitagliptin+irradiation group by using a randomized block design, with five mice in each group. The mice in the irradiation and sitagliptin+irradiation groups received 7 Gy 137Cs γ-ray total body irradiation. Sitagliptin was administered to the latter via gavage 2 h after the irradiation. The dose was 10 mg/kg, and gavage infusion was continuous. Sitagliptin administration lasted for 7 days. The control and irradiation groups were given the same volume of normal saline. On the 30th day after irradiation, peripheral blood was collected for blood routine examination. After the mice were sacrificed via cervical dislocation, bone marrow cells were collected to determine the numbers of nucleated cells, hematopoietic stem cells (HSC), and hematopoietic progenitor cells (HPC), along with their reactive oxygen species (ROS) levels. The number of colony-forming units granulocyte-macrophage (CFU-GM) clones was also determined. Data between two groups were compared via independent sample t-test.
Results Compared with those of the control group, the numbers of bone marrow nucleated cells, white blood cells, red blood cells, platelets, hemoglobin, and hematocrit of the irradiation group were significantly reduced (t=3.476−12.200, all P<0.05). The number and percentage of HSC and HPC were significantly reduced (t=3.174−5.287, all P<0.05). The level of ROS in HSC increased significantly (1980.6±309.3 vs. 3994.5±1119.0, t=3.904, P<0.05). The number of bone marrow cell CFU-GM clones was significantly decreased (66.2±5.3 vs. 30.8±3.9, t=13.240, P<0.05). Compared with the irradiation group, the number of bone marrow nucleated cells ((8.0±1.0)×106 vs. (11.0±0.4)×106, t=4.593, P<0.05) and white blood cells ((3.0±0.2)×109/L vs. (3.9±0.3)×109/L, t=7.020, P<0.05) increased (t=4.593, P<0.05) in the sitagliptin+irradiation group. The number of HPC (33 724.4±10 594.9 vs. 101 637.6±17 240.5, t=5.951, P<0.05) and percentage ((5.6±1.0%) vs. (11.5±3.0)%, t=4.163, P<0.05) also increased. The ROS level in HSC decreased (3994.5±1119.0 vs. 2415.7±122.9, t=2.375, P<0.05), whereas the number of the bone marrow cell CFU-GM clones increased (30.8±3.9 vs. 38.2±4.4, t=2.964, P<0.05).
Conclusion Sitagliptin exerts a certain therapeutic effect on hematopoietic system injury in mice after 7 Gy γ-ray irradiation.