PMID- 34210334 OWN - NLM STAT- MEDLINE DCOM- 20211102 LR - 20240402 IS - 1749-799X (Electronic) IS - 1749-799X (Linking) VI - 16 IP - 1 DP - 2021 Jul 1 TI - Ischemic postconditioning ameliorates acute kidney injury induced by limb ischemia/reperfusion via transforming TLR4 and NF-kappaB signaling in rats. PG - 416 LID - 10.1186/s13018-021-02565-5 [doi] LID - 416 AB - BACKGROUND: The present study investigated the influence of ischemic postconditioning (I-postC) on the adjustment of renal injury after limb ischemia-reperfusion (I/R) injury, to elucidate the mechanisms of the Toll-like receptor 4 (TLR 4)/NF-kappaB signaling pathway using histopathological and immunohistochemical methods. METHODS: Male Sprague-Dawley rats were randomly assigned to five groups (numbered from 1 to 5): the sham group (Group 1, only the anesthesia procedure was conducted without limb I/R), the I/R group (Group 2, 4 h of reperfusion was conducted following 4 h limb ischemia under anesthesia), the I/R + I-postC group (Group 3, 4 h of ischemia and 4 h of reperfusion was conducted; before perfusion, 5 min of limb ischemia and 5 min of reperfusion were performed in the rats and repeated 3 times), the I/R + TAK group (Group 4, rats were injected with TLR4 antagonist TAK through the caudal vein before limb ischemia and reperfusion under anesthesia), the TAK group (Group 5, rats were injected with TAK, and the anesthesia procedure was conducted without limb I/R). Histological changes in the kidney in different groups were observed, and the extent of tubular injury was assessed. Changes in biochemical indexes and the expression of inflammatory factors, TLR4, and NF-kappaB were also evaluated. RESULTS: Compared with rats in the I/R group, the secretion of inflammatory factors and the expression levels of TLR4 and NF-kappaB were decreased in rats in the I/R + I-postC group. Histological analysis revealed renal injury, including inflammatory cell infiltration, dilatation of the tubuli lumen, congestion in glomerular capillaries, degeneration of tubuli epithelial cells, and necrosis was ameliorated by I-postC. Immunohistochemical studies showed that I/R-induced elevation in TLR4 and NF-kappaB expression was reduced by I-postC treatment. Moreover, the expression levels of TLR4, NF-kappaB, and inflammatory factors in rats in the I/R + TAK group were also decreased, and the renal pathological lesion was alleviated, which was similar to that in rats in the I/R + I-postC group. CONCLUSIONS: The present findings suggest that I-postC can reduce tissue injury and kidney inflammation induced by limb I/R injury, possibly via inhibition of the TLR4 and NF-kappaB pathways. FAU - Liu, Zhongdi AU - Liu Z AD - National Center for Trauma Medicine, Ministry of Education Key Laboratory of Trauma and Neural Regeneration, Trauma Medicine Center, Peking University People's Hospital, No. 11 XiZhiMen South Street, Xicheng District, Beijing, 100044, China. liu_zhongdi@126.com. FAU - Huang, Wei AU - Huang W AD - National Center for Trauma Medicine, Ministry of Education Key Laboratory of Trauma and Neural Regeneration, Trauma Medicine Center, Peking University People's Hospital, No. 11 XiZhiMen South Street, Xicheng District, Beijing, 100044, China. FAU - Chen, Yifan AU - Chen Y AD - National Center for Trauma Medicine, Ministry of Education Key Laboratory of Trauma and Neural Regeneration, Trauma Medicine Center, Peking University People's Hospital, No. 11 XiZhiMen South Street, Xicheng District, Beijing, 100044, China. FAU - Du, Zhe AU - Du Z AD - National Center for Trauma Medicine, Ministry of Education Key Laboratory of Trauma and Neural Regeneration, Trauma Medicine Center, Peking University People's Hospital, No. 11 XiZhiMen South Street, Xicheng District, Beijing, 100044, China. FAU - Zhu, Fengxue AU - Zhu F AD - National Center for Trauma Medicine, Ministry of Education Key Laboratory of Trauma and Neural Regeneration, Trauma Medicine Center, Peking University People's Hospital, No. 11 XiZhiMen South Street, Xicheng District, Beijing, 100044, China. FAU - Wang, Tianbing AU - Wang T AD - National Center for Trauma Medicine, Ministry of Education Key Laboratory of Trauma and Neural Regeneration, Trauma Medicine Center, Peking University People's Hospital, No. 11 XiZhiMen South Street, Xicheng District, Beijing, 100044, China. FAU - Jiang, Baoguo AU - Jiang B AD - National Center for Trauma Medicine, Ministry of Education Key Laboratory of Trauma and Neural Regeneration, Trauma Medicine Center, Peking University People's Hospital, No. 11 XiZhiMen South Street, Xicheng District, Beijing, 100044, China. LA - eng GR - RDY 2020-23/Peking University People's Hospital Scientific Research Development Funds/ GR - BMU2019LCKXJ005/Peking University Clinical Scientist Program and the Fundamental Research Funds for the Central Universities/ PT - Journal Article DEP - 20210701 PL - England TA - J Orthop Surg Res JT - Journal of orthopaedic surgery and research JID - 101265112 RN - 0 (NF-kappa B) RN - 0 (Tlr4 protein, rat) RN - 0 (Toll-Like Receptor 4) SB - IM MH - Acute Kidney Injury/etiology/genetics/*therapy MH - Animals MH - Disease Models, Animal MH - Hindlimb/*blood supply/injuries MH - *Ischemic Postconditioning MH - Kidney/metabolism MH - Male MH - NF-kappa B/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Reperfusion Injury/complications/genetics/*therapy MH - Signal Transduction/*genetics MH - Toll-Like Receptor 4/metabolism PMC - PMC8247170 OTO - NOTNLM OT - Ischemic postconditioning OT - Kidney OT - Limb ischemia OT - Reperfusion injury COIS- The authors declare that they have no conflicts of interest. EDAT- 2021/07/03 06:00 MHDA- 2021/11/03 06:00 PMCR- 2021/07/01 CRDT- 2021/07/02 05:38 PHST- 2021/04/15 00:00 [received] PHST- 2021/06/17 00:00 [accepted] PHST- 2021/07/02 05:38 [entrez] PHST- 2021/07/03 06:00 [pubmed] PHST- 2021/11/03 06:00 [medline] PHST- 2021/07/01 00:00 [pmc-release] AID - 10.1186/s13018-021-02565-5 [pii] AID - 2565 [pii] AID - 10.1186/s13018-021-02565-5 [doi] PST - epublish SO - J Orthop Surg Res. 2021 Jul 1;16(1):416. doi: 10.1186/s13018-021-02565-5.