Role of Bone Marrow Mesenchymal Stromal Cells in Attenuating Inflammatory Reaction in Lipopolysaccaride-induced Acute Kidney Injury of Rats Associated with TLR4-NF-kappa B Signaling Pathway Inhibition
机构:[1]Kunming Med Univ, Peoples Hosp Yunnan Prov 2, Affiliated Hosp 4, Dept Intens Care Unit, 176 Qingnian Rd, Kunming 650021, Yunnan, Peoples R China[2]First Peoples Hosp Yunnan Prov, Dept Obstet, Kunming, Yunnan, Peoples R China外科片产科云南省第一人民医院[3]First Hosp Yunnan Prov, Dept Anesthesia, Kunming, Yunnan, Peoples R China[4]Kunming Gen Hosp Chengdu Mil Reg, Ctr Cell Biol Therapy, Kunming, Yunnan, Peoples R China[5]Qingdao Univ, Dept Anesthesia, Affiliated Hosp, Qingdao, Shandong, Peoples R China
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摘要:
Bone marrow mesenchymal stromal cells (BMSCs) have positive therapeutic effects on inflammation associated diseases. However, the underlying mechanism is largely unknown. This study was conducted to investigate whether BMSCs could alleviate the inflammation reaction in lipopolysaccaride (LPS)-induced acute kidney injury (septic-AKI) of rats via inhibition of toll-like receptors (TLR4)-nuclear factor-kappa B (NF-kappa B) signaling pathway. The septic-AKI rat model was established by injecting the 1 ml/mg LPS through the femoral vein. Based on this model, rats were subjected to BMSC transplantation, PDTC (a kind of NF-kappa B inhibitor) administration alone, and combined treatment of the first two together. Results showed that LPS treatment caused the increases of the concentration of blood urea nitrogen (BUN) and serum creatinine (SCr), accompanied by tissue injury and the up-regulation of TLR4 and NF-kappa B, that was its key downstream signaling molecule, in both mRNA and protein level. Notably, it has been found that BMSCs transplantation significantly reversed the already upregulated concentration of BUN and SCr, dramatically attenuated the event of the tissue injury, and prominently reduced mortality after AKI. These were paralleled by down-regulation of the level of TLR4 and NF-kappa B. These effects of BMSCs transplantation were similar to those of PDTC treatment. Importantly, the effects in the combination therapy of BMSCs transplantation and PDTC group were much stronger than those of either BMSCs or PDTC used alone. These findings suggest that BMSCs transplantation contributes to therapeutic effects in LPS-induced AKI rat model, and that the most obvious effects occurred in the combined treatment group, with BMSCs and PDTC together, which was tightly associated with inhibition of the TLR4-NF-kappa B signaling pathway.
基金:
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81360289]; Association Foundation Program of Yunnan Provincial science, Technology Department and Kunming Medicine University [2017FE468(-180), 2017FE467(-194), 2015FB079, 2013FB185, 2012FB076]; Yunnan health training project of high level talents [H-2017060]; Xu Jun expert workstation of the Second People's Hospital of Yunnan Province [2017IC025]; Department of the Clinical Laboratory of Kunming General Hospital of Chengdu Military Region
第一作者机构:[1]Kunming Med Univ, Peoples Hosp Yunnan Prov 2, Affiliated Hosp 4, Dept Intens Care Unit, 176 Qingnian Rd, Kunming 650021, Yunnan, Peoples R China
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通讯作者:
通讯机构:[1]Kunming Med Univ, Peoples Hosp Yunnan Prov 2, Affiliated Hosp 4, Dept Intens Care Unit, 176 Qingnian Rd, Kunming 650021, Yunnan, Peoples R China[*1]Department of the Intensive Care Unit, The Fourth Affiliated Hospital of Kunming Medical University (The Second People’s Hospital of Yunnan Province), No. 176 Qingnian Road, Kunming, Yunnan Province, 650021, China
推荐引用方式(GB/T 7714):
Xiu Guang-hui,Zhou Xia,Li Xiu-ling,et al.Role of Bone Marrow Mesenchymal Stromal Cells in Attenuating Inflammatory Reaction in Lipopolysaccaride-induced Acute Kidney Injury of Rats Associated with TLR4-NF-kappa B Signaling Pathway Inhibition[J].ANNALS OF CLINICAL AND LABORATORY SCIENCE.2018,48(6):743-750.
APA:
Xiu, Guang-hui,Zhou, Xia,Li, Xiu-ling,Chen, Xian-zhong,Li, Bing-qin...&Ling, Bin.(2018).Role of Bone Marrow Mesenchymal Stromal Cells in Attenuating Inflammatory Reaction in Lipopolysaccaride-induced Acute Kidney Injury of Rats Associated with TLR4-NF-kappa B Signaling Pathway Inhibition.ANNALS OF CLINICAL AND LABORATORY SCIENCE,48,(6)
MLA:
Xiu, Guang-hui,et al."Role of Bone Marrow Mesenchymal Stromal Cells in Attenuating Inflammatory Reaction in Lipopolysaccaride-induced Acute Kidney Injury of Rats Associated with TLR4-NF-kappa B Signaling Pathway Inhibition".ANNALS OF CLINICAL AND LABORATORY SCIENCE 48..6(2018):743-750