Toll-like receptor agonist CBLB502 protects against radiation-induced intestine injury in mice
Radiation-induced intestinal injury is one of the most common complications of abdominal and pelvic radiotherapy. Severe intestinal injury caused by ionizing radiation (IR) has a high mortality rate, which is a worldwide problem requiring urgent attention. IR can cause intestinal tissue damage, inflammatory cell infiltration and pro-inflammatory cytokine release. However, methods to protect against radiation-induced intestinal injury are limited. CBLB502, a Toll-like receptor 5 (TLR5) agonist from Salmonella flagellin, has radioprotective effects on various tissues and organs. In order to further explore the molecular mechanism of IR-induced intestinal injury and the mechanism of protective effect of CBLB502 on IR-induced intestinal injury, mice were given CBLB502 and irradiated with different doses at different times. The survival rate, body weight, hemogram and histopathology of the mice were analyzed. The results showed that CBLB502 before IR can reduce intestinal injury induced by IR. RNA-seq analysis showed that different doses and different time of IR induced different damage mechanisms to promote gene regulation patterns. In addition, CBLB502 exerts its protective effect on IR-induced intestinal injury mainly through biological processes such as immune response. Notably, CBLB502 protected against intestinal injury only after IR, and might play a protective role by reversing the regulation of IR-induced genes. Therefore, this paper basically describes the mechanism of IR-induced intestinal injury and the potential molecular protective mechanism of CBLB502, which provides a basis for further research on functional genes and molecular mechanisms that mediate protection against IR-induced injury in the future. Overall design: C57BL/6 male mice (6-8 weeks old) were maintained in SFP room under light:dark = 1:1. They were randomly divided into 7 groups: irradiated with 6Gy and sampled at 6h (6Gy6h), 15Gy6h, 15Gy24h, 15Gy3d, treated with radioprotectant CBLB502, pretreated with CBLB502 at 0.5h before 15Gy (15Gy+CBLB502), PBS used as control for CBLB502 (PBS only), 10 mice in each group. Animals were irradiated with 60Co ?-rays radiation source at the Beijing Institute of Radiation Medicine at a dose rate of 72R/min.