Paricalcitol attenuates intestinal ischemia-reperfusion injury in mice through HMGB1/TLR4/NF-κB signaling pathway / 中国临床药理学与治疗学

ABSTRACT

AIM: To observe the effect of paricalcitol on intestinal ischemia-reperfusion injury, and to explore the relationship with HMGB1/TLR4/NF-κB signaling pathway. METHODS: Twenty-four SPF-grade healthy adult male C57BL/6J mice were divided into 4 groups (n=6) by random number table sham operation group (S group), paricalcitol pretreatment+sham operation group (SP group), intestinal ischemia-reperfusion group (IR group) and paricalcitol ischemic preconditioning group (P group). S group and SP group were separated the superior mesenteric artery, IR group and P group were clamped the superior mesenteric artery for 45 minutes and then followed by reperfusion for 2 hours to establish the intestinal ischemia-reperfusion model; SP group and P group were intraperitoneally injected with 0.3 μg/kg paricalcitol 24 hours before surgery, and the other two groups were given equal volume of normal saline. The mice were sacrificed at 2 h after reperfusion, and the intestinal tissue was obtained 5 cm from the terminal ileum. The pathological results were observed under light microscope. The intestinal mucosal injury was scored according to the Chiu's scoring standard. The intestinal tissue diamine oxidase (DAO) and tumor were detected by ELISA. Necrosis factor α (TNF-α) and interleukin 6 (IL-6) content; Western blot was used to detect the expression levels of HMGB1, TLR4 and NF-κB p65 protein in small intestine tissues.RESULTS: Compared with S group and SP group, Chiu's score was increased, the expression of Dao, TNF-α and IL-6 were increased, as well as the expression of HMGB1, TLR4 and NF-κB p65 protein increased significantly in IR group (P< 0.05); Compared with IR group, Chiu's score was decreased, the expression of Dao, TNF-α and IL-6 were decreased, as well as the expression of HMGB1, TLR4 and NF-κB p65 protein decreased significantly in P group (P< 0.05). CONCLUSION: Paricalcitol can alleviate intestinal ischemia-reperfusion injury by inhibiting HMGB1/TLR4/NF-κB signaling pathway and playing an anti-inflammatory role.