Ischemic postconditioning ameliorates acute kidney injury induced by limb ischemia/reperfusion via transforming TLR4 and NF-κB signaling in rats
Abstract 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-κB signaling pathway using histopathological and...
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| Format: | Article |
| Language: | English |
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BMC
2021-07-01
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| Series: | Journal of Orthopaedic Surgery and Research |
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| Online Access: | https://doi.org/10.1186/s13018-021-02565-5 |
| _version_ | 1818474887643136000 |
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| author | Zhongdi Liu Wei Huang Yifan Chen Zhe Du Fengxue Zhu Tianbing Wang Baoguo Jiang |
| author_facet | Zhongdi Liu Wei Huang Yifan Chen Zhe Du Fengxue Zhu Tianbing Wang Baoguo Jiang |
| author_sort | Zhongdi Liu |
| collection | DOAJ |
| description | Abstract 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-κB 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-κB 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-κB 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-κB expression was reduced by I-postC treatment. Moreover, the expression levels of TLR4, NF-κB, 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-κB pathways. |
| first_indexed | 2024-04-14T04:42:31Z |
| format | Article |
| id | doaj.art-2be953cf25cd45489202ef61cb236b84 |
| institution | Directory Open Access Journal |
| issn | 1749-799X |
| language | English |
| last_indexed | 2024-04-14T04:42:31Z |
| publishDate | 2021-07-01 |
| publisher | BMC |
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| series | Journal of Orthopaedic Surgery and Research |
| spelling | doaj.art-2be953cf25cd45489202ef61cb236b842022-12-22T02:11:35ZengBMCJournal of Orthopaedic Surgery and Research1749-799X2021-07-011611910.1186/s13018-021-02565-5Ischemic postconditioning ameliorates acute kidney injury induced by limb ischemia/reperfusion via transforming TLR4 and NF-κB signaling in ratsZhongdi Liu0Wei Huang1Yifan Chen2Zhe Du3Fengxue Zhu4Tianbing Wang5Baoguo Jiang6National Center for Trauma Medicine, Ministry of Education Key Laboratory of Trauma and Neural Regeneration, Trauma Medicine Center, Peking University People’s HospitalNational Center for Trauma Medicine, Ministry of Education Key Laboratory of Trauma and Neural Regeneration, Trauma Medicine Center, Peking University People’s HospitalNational Center for Trauma Medicine, Ministry of Education Key Laboratory of Trauma and Neural Regeneration, Trauma Medicine Center, Peking University People’s HospitalNational Center for Trauma Medicine, Ministry of Education Key Laboratory of Trauma and Neural Regeneration, Trauma Medicine Center, Peking University People’s HospitalNational Center for Trauma Medicine, Ministry of Education Key Laboratory of Trauma and Neural Regeneration, Trauma Medicine Center, Peking University People’s HospitalNational Center for Trauma Medicine, Ministry of Education Key Laboratory of Trauma and Neural Regeneration, Trauma Medicine Center, Peking University People’s HospitalNational Center for Trauma Medicine, Ministry of Education Key Laboratory of Trauma and Neural Regeneration, Trauma Medicine Center, Peking University People’s HospitalAbstract 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-κB 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-κB 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-κB 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-κB expression was reduced by I-postC treatment. Moreover, the expression levels of TLR4, NF-κB, 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-κB pathways.https://doi.org/10.1186/s13018-021-02565-5Limb ischemiaReperfusion injuryKidneyIschemic postconditioning |
| spellingShingle | Zhongdi Liu Wei Huang Yifan Chen Zhe Du Fengxue Zhu Tianbing Wang Baoguo Jiang Ischemic postconditioning ameliorates acute kidney injury induced by limb ischemia/reperfusion via transforming TLR4 and NF-κB signaling in rats Journal of Orthopaedic Surgery and Research Limb ischemia Reperfusion injury Kidney Ischemic postconditioning |
| title | Ischemic postconditioning ameliorates acute kidney injury induced by limb ischemia/reperfusion via transforming TLR4 and NF-κB signaling in rats |
| title_full | Ischemic postconditioning ameliorates acute kidney injury induced by limb ischemia/reperfusion via transforming TLR4 and NF-κB signaling in rats |
| title_fullStr | Ischemic postconditioning ameliorates acute kidney injury induced by limb ischemia/reperfusion via transforming TLR4 and NF-κB signaling in rats |
| title_full_unstemmed | Ischemic postconditioning ameliorates acute kidney injury induced by limb ischemia/reperfusion via transforming TLR4 and NF-κB signaling in rats |
| title_short | Ischemic postconditioning ameliorates acute kidney injury induced by limb ischemia/reperfusion via transforming TLR4 and NF-κB signaling in rats |
| title_sort | ischemic postconditioning ameliorates acute kidney injury induced by limb ischemia reperfusion via transforming tlr4 and nf κb signaling in rats |
| topic | Limb ischemia Reperfusion injury Kidney Ischemic postconditioning |
| url | https://doi.org/10.1186/s13018-021-02565-5 |
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