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目的:评价小鼠内毒素性肺损伤时沉默信息调节因子2相关酶3(SIRT3)与线粒体功能的关系。方法:清洁级健康成年雄性野生C57BL/6(SIRT3n +/+)小鼠20只，SIRT3基因敲除(SIRT3n -/-)小鼠20只，体重20~25 g，6~8周龄，采用随机数字表法，将SIRT3n +/+小鼠和SIRT3n -/-小鼠分别分为4组(n n＝5)：空白对照组(C组、SIRT3n -/- C组)、内毒素性肺损伤组(L组、SIRT3n -/- L组)、内毒素性肺损伤+白藜芦醇组(L+R组、SIRT3n -/- L+R组)、白藜芦醇组(R组、SIRT3n -/- R组)。L+R组、R组、SIRT3n -/- L+R组和SIRT3n -/- R组腹腔注射白藜芦醇15 mg/kg，1次/d，连续7 d，其余组给予等容量生理盐水。第7天注射白藜芦醇后30 min时L+R组与SIRT3n -/- L+R组、L组与SIRT3n -/- L组于相应时点尾静脉注射LPS 15 mg/kg制备内毒素性肺损伤模型，其余组注射等容量生理盐水。注射生理盐水或LPS后12 h时，于眼眶静脉丛采血，分别采用二甲酚橙法和ABTS比色法测定血清总氧化状态(TOS)和总抗氧化状态(TAS)水平，计算氧化应激指数(OSI)；小鼠安乐死后取肺组织，行肺损伤评分，采用JC-1法测定线粒体膜电位(MMP)，采用特异性荧光探针法测定细胞氧消耗率(OCR)，采用Western blot法测定SIRT3表达水平。n 结果:与C组或SIRT3n -/- C组比较，L组与L+R组、SIRT3n -/- L组与SIRT3n -/- L+R组肺损伤评分、血清TOS浓度和OSI升高，TAS浓度、MMP和OCR降低，SIRT3表达下调(n P<0.05)。与L组比较，L+R组肺损伤评分、血清TOS浓度和OSI降低，TAS浓度、MMP及OCR升高，SIRT3表达上调，而SIRT3n -/- L组肺损伤评分、血清TOS浓度和OSI升高，TAS浓度、MMP及OCR降低，SIRT3表达下调(n P<0.05)。与L+R组比较，SIRT3n -/- L+R组肺损伤评分、血清TOS浓度和OSI升高，TAS浓度、MMP及OCR降低，SIRT3表达下调(n P0.05)。n 结论:SIRT3表达下调可导致线粒体功能受损，参与小鼠内毒素性肺损伤的病理生理机制。“,”Objective:To evaluate the relationship between silent information regulator 2 homologue 3 (SIRT3) and mitochondrial function in mice with endotoxin-induced lung injury.Methods:Twenty clean-grade healthy adult male wild C57BL/6 (SIRT3n + /+ ) mice, 20 SIRT3 knockout (SIRT3n -/-) mice, weighing 20-25 g, aged 6-8 weeks, were studied.SIRT3n + /+ mice and SIRT3n -/- mice were divided into 4 groups (n n=5 each) according to the random number table method: blank control group (group C, group SIRT3n -/-C), endotoxin-induced lung injury group (group L, group SIRT3n -/-L), endotoxin-induced lung injury plus resveratrol group (group L+ R, group SIRT3n -/-L+ R), and resveratrol group (group R, group SIRT3n -/-R). Resveratrol 15 mg/kg was intraperitoneally injected once a day for 7 consecutive days in L+ R, R, SIRT3n -/-L+ R and SIRT3n -/-R groups, while the equal volume of normal saline was injected in the rest groups.Lipopolysaccharid 15 mg/kg was injected n via the tail vein to develop a mouse model of endotoxin-induced lung injury at 30 min after resveratrol injection on 7th day, in L+ R and SIRT3n -/-L+ R groups and at the corresponding time points in L and SIRT3n -/-L groups, while the equal volume of normal saline was injected in the other groups.Blood samples were collected from the orbital venous plexus at 12 h after injection of normal saline or lipopolysaccharid for determination of serum total oxidation state (TOS) and total antioxidant state (TAS) levels by the xylenol orange method and ABTS colorimetric method, and the oxidative stress index (OSI) was calculated.After the mice were sacrificed, the lung tissues were taken for microscopic examination of the pathological changes which were scored and for determination of the mitochondrial membrane potential (MMP) (by JC-1 method), cellular oxygen consumption rate (OCR) (by the specific fluorescent probe method), and expression of SIRT3 (by Western blot).n Results:Compared with group C or group SIRT3n -/-C, the lung injury score, serum TOS concentration and OSI were significantly increased, TAS concentration, MMP and OCR were decreased, and SIRT3 expression was down-regulated in L, L+ R, SIRT3n -/-L and SIRT3n -/-L+ R groups (n P<0.05). Compared with group L, the lung injury score, serum TOS concentration and OSI were significantly decreased, TAS concentration, MMP and OCR were increased, and SIRT3 expression was up-regulated in group L+ R, and lung injury score, serum TOS concentration and OSI were significantly increased, TAS concentration, MMP and OCR were decreased, and SIRT3 expression was down-regulated in group SIRT3n -/-L (n P<0.05). Compared with group L+ R, the lung injury score, serum TOS concentration and OSI were significantly increased, the TAS concentration, MMP and OCR were decreased, and the expression of SIRT3 was down-regulated in group SIRT3n -/- L+ R (n P0.05).n Conclusions:Down-regulation of SIRT3 expression can lead to impaired mitochondrial function, which is involved in the pathophysiological mechanism of endotoxin-induced lung injury.