role of tlr4nf-κb in damage to intestinal mucosa barrier function and bacterial translocation in rats exposed to hypoxiatlr4nf-κb在肠道粘膜屏障功能损害和细菌易位的老鼠暴露于低氧.pdfVIP

Role of TLR4/NF-kB in Damage to Intestinal Mucosa Barrier Function and Bacterial Translocation in Rats Exposed to Hypoxia Han Luo1,2, Ping Guo1,2, Qiquan Zhou1,2* 1 Department of High Altitude Diseases, College of High Altitude Military Medicine, Third Military Medical University, Chongqing, China, 2 Key Laboratory of High Altitude Medicine of Ministry of Education and Key Laboratory of High Altitude Medicine of PLA, Chongqing, China Abstract The role of Toll-like receptor 4 (TLR4)/nuclear factor-kappa-B (NF-kB) in intestinal mucosal barrier damage and bacterial translocation under hypoxic exposure is unclear. Here, we investigated their role using an acute hypobaric hypoxia model. Adult Sprague-Dawley rats were divided into control (C), hypoxia (H), hypoxia+NF-kB inhibitor pyrrolidinedithiocarbamic acid (PDTC) (100 mg. kg) (HP), hypoxia+0.5 mg/kg lipopolysaccharide (HPL), and hypoxia+PDTC+LPS (HPL) group. Except control group, other four groups were placed in a hypobaric chamber set at 7000 m. Samples were collected at 72 h after pressure reduction. Damage in ultrastructure of the intestinal tract was examined by transmission electron microscopy and bacterial translocation was detected by cultivation. Kinetic turbidimetric assay was used to measure the serum LPS. ELISA was performed to detect TNF-a and IL-6 serum concentrations. Fluorescent quantitative RT-PCR was used to measure TLR4 mRNA levels was measured using quantitative RT-PCR and protein of NF-kB p65 was measured by western blotting. Different degrees of intestinal mucosa damage were observed in groups H and HL. The damage was significantly alleviated after blockage of the TLR4/NF-kB signaling pathway. PDTC- treatment also reversed hyoxia- and LPS-induced bacterial translocation rate and increased serum levels of LPS, TNF-a, and IL-6. TLR4 mRNA lev