Propofol increases bone morphogenetic protein-7 and decreases oxidative stress in sepsis-induced acute kidney injury
Propofol increases bone morphogenetic protein-7 and decreases oxidative stress in sepsis-induced acute kidney injury
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DOI：
10.1093/ndt/gfq572
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发表时间：
2011-04-01
影响因子：
6.1
通讯作者：
Yeh, Ching-Hua
中科院分区：
文献类型：
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作者：
Hsing, Chung-Hsi;Chou, Willy;Yeh, Ching-Hua
背景。促炎细胞因子和自由基损伤肾组织导致急性肾损伤（AKI）在败血症。骨形态发生蛋白-7 （BMP-7）抑制肿瘤坏死因子(TNF)- α诱导的炎症反应并保护肾脏免受损伤。镇静剂异丙酚具有免疫调节和抗氧化特性。本研究探讨异丙酚是否能降低盲肠结扎穿刺（CLP）小鼠的AKI，并探讨其可能的机制。小鼠在CLP手术后立即和12小时用异丙酚或生理盐水治疗。观察CLP术后24 h小鼠肾损伤、存活率及细胞因子表达情况。在体外，用异丙酚处理脂多糖（LPS）刺激的大鼠系膜细胞（RMCs）或过氧化氢（H2O2）暴露的小鼠肾上皮细胞（M1）。采用RT-PCR法检测CLP小鼠肾、rmc和M1细胞中BMP-7、tnf - α和单核细胞趋化蛋白(MCP)-1的表达。分析RMCs和M1细胞的自由基生成和细胞死亡情况。western blotting检测lps刺激下RMCs中核因子(NF)- κ B和过氧化物酶体增殖物激活受体(PPAR)- γ的表达。异丙酚增加了CLP小鼠的存活率并改善了AKI。异丙酚增加了CLP小鼠和lps刺激的RMCs肾脏中BMP-7的表达，但降低了tnf - α和MCP-1的表达。异丙酚还能抑制lps刺激的RMCs中自由基的产生和细胞死亡，并降低h2o2暴露的M1细胞中tnf - α的表达和细胞死亡。此外，异丙酚降低了lps刺激的rmc中NF-kappa B的表达，但增加了ppar - γ的表达。异丙酚治疗可通过提高BMP-7表达、降低炎症因子和抑制氧化应激来保护肾脏免受败血症引起的AKI。
Background. Pro-inflammatory cytokines and free radicals damage renal tissue leading to acute kidney injury (AKI) during sepsis. Bone morphogenetic protein-7 (BMP-7) represses tumour necrosis factor (TNF)-alpha-induced inflammatory responses and protects kidney from injury. The sedative agent, propofol, has immunomodulatory and antioxidative properties. The present study investigated whether propofol could reduce AKI in caecal ligation and puncture (CLP) mice and the possible mechanism behind this.Methods. Mice were treated with propofol or saline immediately and 12 h after CLP surgery. Kidney injury, survival and cytokine expressions of CLP mice were observed 24 h after CLP surgery. In vitro, lipopolysaccharide (LPS)-stimulated rat mesangial cells (RMCs) or hydrogen peroxide (H2O2)-exposed murine kidney epithelial cells (M1) were treated with propofol. The expression of BMP-7, TNF-alpha and monocyte chemotactic protein (MCP)-1 in CLP mice kidney, RMCs or M1 cells was determined by RT-PCR. Free radical generation and cell death of RMCs and M1 cells were analysed. Nuclear factor (NF)-kappa B and peroxisome proliferator-activated receptor (PPAR)-gamma expressions in LPS-stimulated RMCs were determined by western blotting.Results. Propofol increased survival and ameliorated AKI in CLP mice. Propofol increased BMP-7 expression but decreased TNF-alpha and MCP-1 expressions in the kidney of CLP mice and LPS-stimulated RMCs. Propofol also inhibited free radical generation and cell death in LPS-stimulated RMCs and decreased the TNF-alpha expression and cell death in H2O2-exposed M1 cells. Moreover, propofol decreased NF-kappa B but increased PPAR-gamma expression in LPS-stimulated RMCs.Conclusions. Propofol treatment could protect kidney from sepsis-induced AKI by increasing BMP-7 expression, decreasing inflammatory cytokines and inhibiting oxidative stress.