Issue
Effects of dexmedetomidine pretreatment on rats with sepsis-induced acute kidney injury and miR-146a expression
Corresponding Author(s) : Shuzhou Yin
Cellular and Molecular Biology,
Vol. 66 No. 2: Issue 2
Abstract
The current research aimed to study the effects of dexmedetomidine (DEX) pretreatment on rats with sepsis-induced acute kidney injury (SAKI) and miR-146a expression. The model of SAKI was established through the tail vein injection of lipopolysaccharide (LSP). We used an automatic biochemical analyzer to detect serum urea nitrogen (BUN) and creatinine (Cre) levels. The expression levels of urine KIM-1 and NGAL and serum IL-1β and IL-6 were analyzed by enzyme-linked immunosorbent assay (ELISA). The content and activity of superoxide dismutase (SOD) were detected by the xanthine oxidase method. The content of malondialdehyde (MDA) was determined by the thiobarbituric acid (TBA) method. Reactive oxygen species (ROS) was detected by fluorescent probe DCFH-DA. Catalase (CAT) was detected by potassium permanganate titration. The expression level of miR-146a in the renal tissue and serum was detected by RT-PCR. The expression levels of Nrf2 and HO-1 proteins were detected by Western blot. Compared with those in the model group, rats in the DEX group had significantly lower expression levels of serum BUN, Cre, IL-1β, and IL-6, and oxidant markers MDA and ROS, but significantly higher expression levels of miR-146a and antioxidant markers SOD and CAT. DEX pretreatment could improve the kidney morphology, injury severity, and Nrf2 and HO-1 proteins of rats with SAKI. In conclusion, DEX can improve oxidative stress and inflammatory responses in rats with SAKI, reduce the severity of the renal injury, and up-regulate the expression level of miR-146a.
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- Polat G, Ugan RA, Cadirci E, Halici Z. Sepsis and Septic Shock: Current Treatment Strategies and New Approaches. Eurasian J Med 2017; 49: 53-58.
- Churpek MM, Snyder A, Han X, Sokol S, Pettit N, Howell MD, Edelson DP. Quick Sepsis-related Organ Failure Assessment, Syste¬mic Inflammatory Response Syndrome, and Early Warning Scores for Detecting Clinical Deterioration in Infected Patients outside the Intensive Care Unit. Am J Respir Crit Care Med 2017; 195: 906-911.
- Bellomo R, Kellum JA, Ronco C, Wald R, Martensson J, Maiden M, Bagshaw SM, Glassford NJ, Lankadeva Y, Vaara ST, Schneider A. Acute kidney injury in sepsis. Intensive Care Med 2017; 43: 816- 828.
- Bagshaw SM, George C, Bellomo R. ANZICS Database Manage¬ment Committee: Early Acute Kidney Injury and Sepsis: Multicen¬ter Assessment. Crit Care 2008; 12: R47,.
- Mehta RL, Bouchard J, Soroko SB, Ikizler TA, Paganini EP, Cher¬tow GM, Himmelfarb J. Sepsis as a cause and consequence of acute kidney injury: program to improve care in acute renal disease. Inten¬sive Care Med 2011; 37: 241-248.
- Rajapakse S, Rodrigo C, Rajapakse A, Kirthinanda D, Wijeratne S. Renal replacement therapy in sepsis induced acute renal failure. Saudi J Kidney Dis Transpl 2009; 20: 553-559.
- Anokye-Danso F, Trivedi CM, Juhr D, Gupta M, Cui Z, Tian Y, Zhang Y, Yang W, Gruber PJ, Epstein JA, Morrisey EE. Highly effi¬cient miRNA-mediated reprogramming of mouse and human soma¬tic cells to pluripotency. Cell Stem Cell 2011; 8: 376-388.
- Feng B, Chen S, Gordon AD, Chakrabarti S. miR-146a mediates inflammatory changes and fibrosis in the heart in diabetes. J Mol Cell Cardiol 2017; 105: 70-76.
- Song Y, Dou H, Li X, Zhao X, Li Y, Liu D, Ji J, Liu F, Ding L, Ni Y, HOU Y. Exosomal miR-146a Contributes to the Enhanced Thera¬peutic Efficacy of Interleukin-1β-Primed Mesenchymal Stem Cells Against Sepsis. Stem Cells 2017; 35: 1208-1221.
- Liang H, Liu HZ, Wang HB, Zhong JY, Yang CX, Zhang B. Dex¬medetomidine protects against cisplatin-induced acute kidney injury in mice through regulating apoptosis and inflammation. Inflamm Res 2017; 66: 399-411.
- Kim E, Kim HC, Lee S, Ryu HG, Park YH, Kim JH, Lim YJ, Park HP. Dexmedetomidine confers neuroprotection against tran-sient global cerebral ischemia/reperfusion injury in rats by inhibiting inflammation through inactivation of the TLR-4/NF-κB pathway. Neurosci Lett 2017; 649: 20-27.
- Liang Y, Lin Q, Huang P, Wang Y, Li J, Zhang L and Cao J: Rice Bioactive Peptide Binding with TLR4 To Overcome H2O2-Induced Injury in Human Umbilical Vein Endothelial Cells through NF-κB Signaling. J Agri Food Chem 2018; 66(2): 440-448.
- Wang L, Lin Q, Yang T, Liang Y, Nie Y, Luo Y and Luo F: Oryza¬nol modifies high fat diet-induced obesity, liver gene expression pro¬file, and inflammation response in mice. J Agri Food Chem 2017; 65(38): 8374-8385.
- Lou Y, Shi J, Guo D, Qureshi AK and Song L: Function of PD-L1 in antitumor immunity of glioma cells. Saudi J Boil Sci 2017; 24(4): 803-807.
- Guo T, Lin Q, Li X, Nie Y, Wang L, Shi L and Luo F: Octacosa¬nol attenuates inflammation in both RAW264. 7 macrophages and a mouse model of colitis. J Agri Food Chem 2017; 65(18): 3647-3658.
- Li W, Jia MX, Wang JH, Lu JL, Deng J, Tang JX and Liu C: As¬sociation of MMP9-1562C/T and MMP13-77A/G polymorphisms with non-small cell lung cancer in southern Chinese population. Biomol 2019; 9(3): 107-119.
- Nie Y, Luo F, Wang L, Yang T, Shi L, Li X, Shen J, Xu W, Guo T and Lin Q: Anti-hyperlipidemic effect of rice bran polysaccharide and its potential mechanism in high-fat diet mice. Food Func 2017; 8(11): 4028-4041.
- Lou Y, Yang J, Wang L, Chen X, Xin X and Liu Y: The clini¬cal efficacy study of treatment to Chiari malformation type I with syringomyelia under the minimally invasive surgery of resection of Submeningeal cerebellar Tonsillar Herniation and reconstruction of Cisterna magna. Saudi J Biol Sci 2019; 26(8): 1927-1931.
- Lou Y, Guo D, Zhang H and Song L: Effectiveness of mesenchy¬mal stems cells cultured by hanging drop vs. conventional culturing on the repair of hypoxic-ischemic-damaged mouse brains, measured by stemness gene expression. Open Life Sci 2016; 11(1): 519-523.
- Chen X, Xu Y, Meng L, Chen X, Yuan L, Cai Q, Shi W and Huang G: Non-parametric partial least squares–discriminant analy-sis model based on sum of ranking difference algorithm for tea grade identification using electronic tongue data identify tea grade using e-tongue data. Sens Actuators B Chem 2020; 127924.
- Howell MD, Davis AM. Management of Sepsis and Septic Shock. JAMA 2017; 317: 847-848.
- Souza ACP, Yuen PST, Star RA. Microparticles: markers and mediators of sepsis-induced microvascular dysfunction, immuno¬suppression, and AKI. Kidney International 2015; 87: 1100-1108.
- Zarbock A, Gomez H, Kellum JA. Sepsis-induced AKI revisited: pathophysiology, prevention and future therapies. Curr Opin Crit Care 2014; 20: 588-595.
- Usta U. The effect of dexmedetomidine on liver histopathology in a rat sepsis model: an experimental pilot study. Ulus Travma Acil Cerrahi Derg 2010; 16: 108-112.
- Oztas B, Sahin D, Kir H, Eraldemir FC, Musul M, Kuskay S, Ates N. The effect of leptin, ghrelin, and neuropeptide-Y on serum Tnf-, Il-1, Il-6, Fgf-2, galanin levels and oxidative stress in an ex¬perimental generalized convulsive seizure model. Neuropeptides 2017; 61: 31-37.
- Kang K, Gao Y, Wang SC, Liu HT, Kong WL, Zhang X, Huang R, Qi ZD, Zheng JB, Qu JD, Liu RJ, Liu S, Wang HL, Yu KJ. Dex¬medetomidine protects against lipopolysaccharide-induced sepsis-associated acute kidney injury via an ∂7 nAChR-dependent pathway. Biomed Pharmacother 2018; 106: 210-216.
- Kong X, Thimmulappa R, Kombairaju P, Biswal S. NADPH Oxidase-Dependent Reactive Oxygen Species Mediate Amplified TLR4 Signaling and Sepsis-Induced Mortality in Nrf2-deficient Mice. J Immunol 2010; 185: 569-577.
- Fabrizio FP, Costantini M, Copetti M, la Torre A, Sparaneo A, Fontana A, Poeta L, Gallucci M, Sentinelli S, Graziano P, Parente P, Pompeo V, Salvo LD, Simone G, Papalia R, Picardo F, Balsamo T, Flammia GP, Trombetta D,Pantalone A, Kok K, Paranita F, Musca¬rella LA, Fazio VM. Keap1/Nrf2 pathway in kidney cancer: frequent methylation of KEAP1 gene promoter in clear renal cell carcinoma. Oncotarget 2017; 8: 11187-11198.
- Song KH, Jung SY, Kho SH, Hwang SG, Ha H, Nam SY, Song JY. Effects of low - dose irra- diation on mice with Escherichia coli - induced sepsis. Toxicol Appl Pharmacol 2017; 15: 17-25.
- Zhou Y, Song Y, Shaikh Z, Li H, Zhang H, Caudle Y, Zheng S, Yan H, Hu D, Stuart C, Yin D. MicroRNA-155 attenuates late sepsis-induced cardiac dysfunction through JNK and β-arrestin 2. Oncotarget 2017; 8: 47317-47329.
- Colbert JF, Ford JA, Haeger SM, Yang Y, Dailey KL, Allison KC, Neudecker V, Evans CM, Richardson VL, Brodsky KS, Faubel S, Eltzschig HK, Schmidt EP, Ginde AA. A Model Specific Role of MicroRNA-223 as a Mediator of Kidney Injury During Experimen¬tal Sepsis. Am J Physiol Renal Physiol 2017; 313: F553-F559.
- Taganov KD, Boldin MP, Chang KJ, Baltimore D. NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses . Proc Natl Acad Sci U S A 2006; 103: 12481-12486.
- Zeng Z, Gong H, Li Y, Jie K, Ding C, Shao Q, Liu F, Zhan Y, Nie C, Zhu W, Qian K. Upregulation of miR-146a contributes to the suppression of inflammatory responses in LPS-induced acute lung injury. Exp Lung Res 2013; 39: 275-282.
- Li C, Fu W, Zhang Y, Zhou L, Mao Z, Lv W, Li J, Zhou Y. Meta-analysis of microRNA-146a rs2910164 G>C polymorphism asso¬ciation with autoimmune diseases susceptibility, an update based on 24 studies. PLoS One 2015; 10: e121918.
- Perry MM, Moschos SA, Williams AE, Shepherd NJ, Larner- Svensson HM, Lindsay MA. Rapid changes in microRNA-146a expression negatively regulate the IL-1beta-induced inflammatory response in human lung alveolar epithelial cells. J Immunol 2008; 180: 5689-5698.
- Nie Y, Luo F and Lin Q: Dietary nutrition and gut microflora: A promising target for treating diseases. Trends Food Sci Technol 2018;75: 72-80.
- Ren Y, Jiao X and Zhang L: Expression level of fibroblast growth factor 5 (FGF5) in the peripheral blood of primary hypertension and its clinical significance. Saudi J Biol Sci 2018; 25(3): 469-473.
References
Polat G, Ugan RA, Cadirci E, Halici Z. Sepsis and Septic Shock: Current Treatment Strategies and New Approaches. Eurasian J Med 2017; 49: 53-58.
Churpek MM, Snyder A, Han X, Sokol S, Pettit N, Howell MD, Edelson DP. Quick Sepsis-related Organ Failure Assessment, Syste¬mic Inflammatory Response Syndrome, and Early Warning Scores for Detecting Clinical Deterioration in Infected Patients outside the Intensive Care Unit. Am J Respir Crit Care Med 2017; 195: 906-911.
Bellomo R, Kellum JA, Ronco C, Wald R, Martensson J, Maiden M, Bagshaw SM, Glassford NJ, Lankadeva Y, Vaara ST, Schneider A. Acute kidney injury in sepsis. Intensive Care Med 2017; 43: 816- 828.
Bagshaw SM, George C, Bellomo R. ANZICS Database Manage¬ment Committee: Early Acute Kidney Injury and Sepsis: Multicen¬ter Assessment. Crit Care 2008; 12: R47,.
Mehta RL, Bouchard J, Soroko SB, Ikizler TA, Paganini EP, Cher¬tow GM, Himmelfarb J. Sepsis as a cause and consequence of acute kidney injury: program to improve care in acute renal disease. Inten¬sive Care Med 2011; 37: 241-248.
Rajapakse S, Rodrigo C, Rajapakse A, Kirthinanda D, Wijeratne S. Renal replacement therapy in sepsis induced acute renal failure. Saudi J Kidney Dis Transpl 2009; 20: 553-559.
Anokye-Danso F, Trivedi CM, Juhr D, Gupta M, Cui Z, Tian Y, Zhang Y, Yang W, Gruber PJ, Epstein JA, Morrisey EE. Highly effi¬cient miRNA-mediated reprogramming of mouse and human soma¬tic cells to pluripotency. Cell Stem Cell 2011; 8: 376-388.
Feng B, Chen S, Gordon AD, Chakrabarti S. miR-146a mediates inflammatory changes and fibrosis in the heart in diabetes. J Mol Cell Cardiol 2017; 105: 70-76.
Song Y, Dou H, Li X, Zhao X, Li Y, Liu D, Ji J, Liu F, Ding L, Ni Y, HOU Y. Exosomal miR-146a Contributes to the Enhanced Thera¬peutic Efficacy of Interleukin-1β-Primed Mesenchymal Stem Cells Against Sepsis. Stem Cells 2017; 35: 1208-1221.
Liang H, Liu HZ, Wang HB, Zhong JY, Yang CX, Zhang B. Dex¬medetomidine protects against cisplatin-induced acute kidney injury in mice through regulating apoptosis and inflammation. Inflamm Res 2017; 66: 399-411.
Kim E, Kim HC, Lee S, Ryu HG, Park YH, Kim JH, Lim YJ, Park HP. Dexmedetomidine confers neuroprotection against tran-sient global cerebral ischemia/reperfusion injury in rats by inhibiting inflammation through inactivation of the TLR-4/NF-κB pathway. Neurosci Lett 2017; 649: 20-27.
Liang Y, Lin Q, Huang P, Wang Y, Li J, Zhang L and Cao J: Rice Bioactive Peptide Binding with TLR4 To Overcome H2O2-Induced Injury in Human Umbilical Vein Endothelial Cells through NF-κB Signaling. J Agri Food Chem 2018; 66(2): 440-448.
Wang L, Lin Q, Yang T, Liang Y, Nie Y, Luo Y and Luo F: Oryza¬nol modifies high fat diet-induced obesity, liver gene expression pro¬file, and inflammation response in mice. J Agri Food Chem 2017; 65(38): 8374-8385.
Lou Y, Shi J, Guo D, Qureshi AK and Song L: Function of PD-L1 in antitumor immunity of glioma cells. Saudi J Boil Sci 2017; 24(4): 803-807.
Guo T, Lin Q, Li X, Nie Y, Wang L, Shi L and Luo F: Octacosa¬nol attenuates inflammation in both RAW264. 7 macrophages and a mouse model of colitis. J Agri Food Chem 2017; 65(18): 3647-3658.
Li W, Jia MX, Wang JH, Lu JL, Deng J, Tang JX and Liu C: As¬sociation of MMP9-1562C/T and MMP13-77A/G polymorphisms with non-small cell lung cancer in southern Chinese population. Biomol 2019; 9(3): 107-119.
Nie Y, Luo F, Wang L, Yang T, Shi L, Li X, Shen J, Xu W, Guo T and Lin Q: Anti-hyperlipidemic effect of rice bran polysaccharide and its potential mechanism in high-fat diet mice. Food Func 2017; 8(11): 4028-4041.
Lou Y, Yang J, Wang L, Chen X, Xin X and Liu Y: The clini¬cal efficacy study of treatment to Chiari malformation type I with syringomyelia under the minimally invasive surgery of resection of Submeningeal cerebellar Tonsillar Herniation and reconstruction of Cisterna magna. Saudi J Biol Sci 2019; 26(8): 1927-1931.
Lou Y, Guo D, Zhang H and Song L: Effectiveness of mesenchy¬mal stems cells cultured by hanging drop vs. conventional culturing on the repair of hypoxic-ischemic-damaged mouse brains, measured by stemness gene expression. Open Life Sci 2016; 11(1): 519-523.
Chen X, Xu Y, Meng L, Chen X, Yuan L, Cai Q, Shi W and Huang G: Non-parametric partial least squares–discriminant analy-sis model based on sum of ranking difference algorithm for tea grade identification using electronic tongue data identify tea grade using e-tongue data. Sens Actuators B Chem 2020; 127924.
Howell MD, Davis AM. Management of Sepsis and Septic Shock. JAMA 2017; 317: 847-848.
Souza ACP, Yuen PST, Star RA. Microparticles: markers and mediators of sepsis-induced microvascular dysfunction, immuno¬suppression, and AKI. Kidney International 2015; 87: 1100-1108.
Zarbock A, Gomez H, Kellum JA. Sepsis-induced AKI revisited: pathophysiology, prevention and future therapies. Curr Opin Crit Care 2014; 20: 588-595.
Usta U. The effect of dexmedetomidine on liver histopathology in a rat sepsis model: an experimental pilot study. Ulus Travma Acil Cerrahi Derg 2010; 16: 108-112.
Oztas B, Sahin D, Kir H, Eraldemir FC, Musul M, Kuskay S, Ates N. The effect of leptin, ghrelin, and neuropeptide-Y on serum Tnf-, Il-1, Il-6, Fgf-2, galanin levels and oxidative stress in an ex¬perimental generalized convulsive seizure model. Neuropeptides 2017; 61: 31-37.
Kang K, Gao Y, Wang SC, Liu HT, Kong WL, Zhang X, Huang R, Qi ZD, Zheng JB, Qu JD, Liu RJ, Liu S, Wang HL, Yu KJ. Dex¬medetomidine protects against lipopolysaccharide-induced sepsis-associated acute kidney injury via an ∂7 nAChR-dependent pathway. Biomed Pharmacother 2018; 106: 210-216.
Kong X, Thimmulappa R, Kombairaju P, Biswal S. NADPH Oxidase-Dependent Reactive Oxygen Species Mediate Amplified TLR4 Signaling and Sepsis-Induced Mortality in Nrf2-deficient Mice. J Immunol 2010; 185: 569-577.
Fabrizio FP, Costantini M, Copetti M, la Torre A, Sparaneo A, Fontana A, Poeta L, Gallucci M, Sentinelli S, Graziano P, Parente P, Pompeo V, Salvo LD, Simone G, Papalia R, Picardo F, Balsamo T, Flammia GP, Trombetta D,Pantalone A, Kok K, Paranita F, Musca¬rella LA, Fazio VM. Keap1/Nrf2 pathway in kidney cancer: frequent methylation of KEAP1 gene promoter in clear renal cell carcinoma. Oncotarget 2017; 8: 11187-11198.
Song KH, Jung SY, Kho SH, Hwang SG, Ha H, Nam SY, Song JY. Effects of low - dose irra- diation on mice with Escherichia coli - induced sepsis. Toxicol Appl Pharmacol 2017; 15: 17-25.
Zhou Y, Song Y, Shaikh Z, Li H, Zhang H, Caudle Y, Zheng S, Yan H, Hu D, Stuart C, Yin D. MicroRNA-155 attenuates late sepsis-induced cardiac dysfunction through JNK and β-arrestin 2. Oncotarget 2017; 8: 47317-47329.
Colbert JF, Ford JA, Haeger SM, Yang Y, Dailey KL, Allison KC, Neudecker V, Evans CM, Richardson VL, Brodsky KS, Faubel S, Eltzschig HK, Schmidt EP, Ginde AA. A Model Specific Role of MicroRNA-223 as a Mediator of Kidney Injury During Experimen¬tal Sepsis. Am J Physiol Renal Physiol 2017; 313: F553-F559.
Taganov KD, Boldin MP, Chang KJ, Baltimore D. NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses . Proc Natl Acad Sci U S A 2006; 103: 12481-12486.
Zeng Z, Gong H, Li Y, Jie K, Ding C, Shao Q, Liu F, Zhan Y, Nie C, Zhu W, Qian K. Upregulation of miR-146a contributes to the suppression of inflammatory responses in LPS-induced acute lung injury. Exp Lung Res 2013; 39: 275-282.
Li C, Fu W, Zhang Y, Zhou L, Mao Z, Lv W, Li J, Zhou Y. Meta-analysis of microRNA-146a rs2910164 G>C polymorphism asso¬ciation with autoimmune diseases susceptibility, an update based on 24 studies. PLoS One 2015; 10: e121918.
Perry MM, Moschos SA, Williams AE, Shepherd NJ, Larner- Svensson HM, Lindsay MA. Rapid changes in microRNA-146a expression negatively regulate the IL-1beta-induced inflammatory response in human lung alveolar epithelial cells. J Immunol 2008; 180: 5689-5698.
Nie Y, Luo F and Lin Q: Dietary nutrition and gut microflora: A promising target for treating diseases. Trends Food Sci Technol 2018;75: 72-80.
Ren Y, Jiao X and Zhang L: Expression level of fibroblast growth factor 5 (FGF5) in the peripheral blood of primary hypertension and its clinical significance. Saudi J Biol Sci 2018; 25(3): 469-473.