·To explore the effect of Tmprss6 gene on radiation-induced intestinal injury in mice.

·7?8 weeks old wild-type (WT) male mice and Tmprss6 knockout (Tmprss6^-/-) mice were randomly divided into non-irradiated (IR) group and groups of 6 h, 24 h, 3.5 d and 7 d post-IR. The IR group received total abdominal X-ray irradiation (TAI) at a dose of 11.5 Gy to establish radiation intestine injury models. H-E staining was performed in the 3.5 d post-IR group, and TUNEL immunofluorescence was performed in the 6 h and 24 h post-IR groups to observe the pathological damage and apoptosis of different intestinal segments, respectively.The levels of iron of different intestinal segments were measured 0, 3.5 and 7 d after TAI, as well as superoxide dismutase (SOD), glutathione (GSH), total antioxidant capacity (T-AOC) and malondialdehyde (MDA). The correlation analysis between iron and each antioxidant index was performed.

·The length of duodenal villi and the number of crypts decreased significantly in both Tmprss6^-/- mice and WT mice 3.5 d after TAI. Meanwhile, the duodenal villi length and crypt count of Tmprss6^-/- mice were lower than those of WT mice (both P<0.05). The number of TUNEL-positive apoptotic cells per crypt in the duodenal segment of Tmprss6^-/- mice was significantly increased compared with that of WT mice 6 and 24 h after TAI (both P<0.05). On the contrary, the length of ileum villi and the count of crypts increased significantly, while the number of TUNEL-positive apoptotic cells decreased significantly in Tmprss6^-/- mice compared with that of WT mice (all P<0.05). The iron content in the duodenum of WT and Tmprss6^-/-mice 7 d after TAI was significantly increased compared with that of non-irradiated mice (both P<0.05). And the iron content of the duodenum in the Tmprss6^-/- mice before and after TAI was significantly higher than that of WT mice at the same time points (all P<0.05). The iron content of the ileum in WT and Tmprss6^-/- mice also increased after TAI. And the increase was statistically significant at 3.5 d post-IR in the WT mice, so was at 7 d post-IR in the Tmprss6^-/- mice (both P<0.05). In addition, the SOD, GSH and T-AOC levels in the duodenum of Tmprss6^-/- mice were lower than those in the WT mice after TAI, while the content of MDA was higher. Among them, the difference of SOD, GSH, MDA and T-AOC levels were statistically significant 3.5 d after TAI (all P<0.05). Contrary to the duodenum, the contents of SOD, GSH, and T-AOC in the ileum of Tmprss6^-/- mice were higher than those in the WT mice, while the content of MDA was lower. Among them, the content of T-AOC, GSH and MDA had a statistically significant difference 3.5 d after TAI (all P<0.05), and the content of SOD had a statistically significant difference 7 d after TAI (P=0.031). The results of correlation analysis showed that there was no significant correlation between the MDA, GSH, SOD and T-AOC levels and the iron content of the small intestine in the non-IR group. The levels of SOD and MDA in the duodenum (r=0.639, r=-0.710, both P<0.05), and T-AOC, MDA and GSH in the ileum (r=-0.817, r=-0.658, r=-0.726, all P<0.05) of WT mice were significantly correlated with their respective iron content after TAI. The levels of MDA, SOD and T-AOC in the duodenum of Tmprss6^-/-mice were significantly correlated with the iron content after TAI (r=-0.606, r=0.771, r=-0.712, all P<0.05), and all the antioxidant indexes of the ileum were not significantly correlated with the iron content.

·The iron level in the small intestine is significantly correlated with the oxidative stress response after irradiation. Tmprss6 gene-deficient mice show increased duodenal iron accumulation and irradiation-induced oxidative stress, and Tmprss6 gene deletion exacerbates duodenal radiation damage.