title: Continuous hemodiafiltration therapy reduces damage of multi-organs by ameliorating of HMGB1/TLR4/NFκB in a dog sepsis model.
abstract: In the present study, we investigated whether CVVH can reduce HMGB1, TLR4, NF-κB and other serum cytokine levels, preventing organ injury in a dog sepsis model. A total of 10 dogs were injected with LPS and treated with either CVVH group (n = 5) or nothing (Control, n = 5) for 24 h. EILSA was used for examining the concentration of TNF-α, IL-6, HMGB 1 and TLR4. The histological change of lung, liver and kidney tissues was determined. The mRNA expression of HMGB1, TLR4 and NF-κB was examined by RT-PCR. The protein of HMGB1 and phosphated NF-κB was examined by Western-blot. The levels of serum HMGB1 came to the peak at 8 h, 16 h and then declined. The LPS-induced increase in HMGB1 level was suppressed by CVVH compared with Control. Likewise, serum TNF-α and IL-6 levels decreased with CVVH along with a significant improvement in the function of main organs. Histologic examination revealed significant reduction in inflammation in lung; liver and kidney tissues harvested 24 h after CVVH compared with Control. The mRNA of HMGB1, TLR4 and NF-κB in the kidney was expressed at high level after LPS administration, which was significantly decreased by CVVH. The increased protein expression of HMGB1 and phosphated NF-κB was reduced after CVVH compared with control. CVVH by reducing the level of HMGB1, TLR4, NF-κB and other cytokines could weaken the cascade of cytokines and restore the immune system, and reduce the damage of important organs in sepsis.
authors.affiliation: Department of Nephrology, Shandong Provincial Hospital, Shandong University Jinan 250021, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Nephrology, Shandong Provincial Hospital, Shandong University Jinan 250021, China.
authors.forename: Shaolan
authors.initials: S
authors.lastname: Shi
authors.affiliation: Department of Nephrology, Shandong Provincial Hospital, Shandong University Jinan 250021, China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Nephrology, Shandong Provincial Hospital, Shandong University Jinan 250021, China.
authors.forename: Kezhou
authors.initials: K
authors.lastname: Yu
authors.affiliation: Department of Nephrology, Shandong Provincial Hospital, Shandong University Jinan 250021, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D004285:Dogs; D004797:Enzyme-Linked Immunosorbent Assay; D024243:HMGB1 Protein / Q000097:blood*; D017583:Hemodiafiltration / Q000379:methods*; D016328:NF-kappa B / Q000097:blood*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018805:Sepsis / Q000097:blood / Q000628:therapy*; D051197:Toll-Like Receptor 4 / Q000097:blood*
chemical_list: D024243:HMGB1 Protein; D016328:NF-kappa B; D051197:Toll-Like Receptor 4
keywords: CVVH; HMGB1; NF-κB; TLR4; sepsis