白藜芦醇可挽救失血性休克后的肾脏线粒体功能。
Resveratrol Rescues Kidney Mitochondrial Function Following Hemorrhagic Shock.
作者信息
Wang Hao, Guan Yuxia, Karamercan Mehmet Akif, Ye Lan, Bhatti Tricia, Becker Lance B, Baur Joseph A, Sims Carrie A
机构信息
*Department of Critical Care Medicine, Qilu Hospital of Shandong University, Jinan, China; †The Trauma Center at Penn and ‡The Center for Resuscitation Science, University of Pennsylvania, Philadelphia, Pennsylvania; §Department of Emergency Medicine, Gazi University School of Medicine, Ankara, Turkey; and ∥Institute for Diabetes, Obesity, and Metabolism and Department of Physiology, Perelman School of Medicine, University of Pennsylvania; and ¶Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
出版信息
Shock. 2015 Aug;44(2):173-80. doi: 10.1097/SHK.0000000000000390.
OBJECTIVE
Hemorrhagic shock may contribute to acute kidney injury (AKI) by profoundly altering renal mitochondrial function. Resveratrol (RSV), a naturally occurring sirtuin 1 (SIRT1) activator, has been shown to promote mitochondrial function and reduce oxidative damage in a variety of aging-related disease states. We hypothesized that RSV treatment during resuscitation would ameliorate kidney mitochondrial dysfunction and decrease oxidative damage following hemorrhagic shock.
METHODS
Using a decompensated hemorrhagic shock model, male Long-Evans rats (n = 6 per group) were killed prior to hemorrhage (sham), at severe shock, and following either lactated Ringer's (LR) resuscitation or LR + RSV resuscitation (RSV: 30 mg/kg). At each time point, blood samples were assayed for arterial blood gases, lactate, blood urea nitrogen, and serum creatinine. Mitochondria were also isolated from kidney samples in order to assess individual electron transport complexes (complexes I, II, and IV) using high-resolution respirometry. Total mitochondria reactive oxygen species were measured using fluorometry, and lipid peroxidation was assessed by measuring 4-hydroxynonenal by Western blot. Quantitative polymerase chain reaction was used quantify mRNA from peroxisome proliferator-activated receptor γ coactivator 1-α (PGC1-α) SIRT1, and proteins known to mitigate oxidative damage and promote mitochondrial biogenesis.
RESULTS
Resveratrol supplementation during resuscitation restored mitochondrial respiratory capacity and decreased mitochondrial reactive oxygen species and lipid peroxidation. Compared with standard LR resuscitation, RSV treatment significantly increased SIRT1 and PGC1-α expression and significantly increased both superoxide dismutase 2 and catalase expression. Although RSV was associated with decreased lactate production, pH, blood urea nitrogen, and serum creatinine values did not differ between resuscitation strategies.
CONCLUSIONS
Resuscitation with RSV significantly restored renal mitochondrial function and decreased oxidative damage following hemorrhagic shock.
目的
失血性休克可能通过深刻改变肾线粒体功能而导致急性肾损伤（AKI）。白藜芦醇（RSV）是一种天然存在的沉默信息调节因子1（SIRT1）激活剂，已被证明可促进线粒体功能，并减少多种与衰老相关疾病状态下的氧化损伤。我们推测，复苏期间给予RSV可改善失血性休克后的肾线粒体功能障碍并减少氧化损伤。
方法
使用失代偿性失血性休克模型，将雄性Long-Evans大鼠（每组n = 6）在出血前（假手术组）、严重休克时以及接受乳酸林格液（LR）复苏或LR + RSV复苏（RSV：30 mg/kg）后处死。在每个时间点，检测血样中的动脉血气、乳酸、血尿素氮和血清肌酐。还从肾样本中分离出线粒体，以便使用高分辨率呼吸测定法评估各个电子传递复合体（复合体I、II和IV）。使用荧光测定法测量总的线粒体活性氧，通过蛋白质印迹法测量4-羟基壬烯醛来评估脂质过氧化。使用定量聚合酶链反应定量过氧化物酶体增殖物激活受体γ共激活因子1-α（PGC1-α）、SIRT1以及已知可减轻氧化损伤和促进线粒体生物发生的蛋白质的mRNA。
结果
复苏期间补充白藜芦醇可恢复线粒体呼吸能力，并减少线粒体活性氧和脂质过氧化。与标准的LR复苏相比，RSV治疗显著增加SIRT1和PGC1-α表达，并显著增加超氧化物歧化酶2和过氧化氢酶的表达。虽然RSV与乳酸生成减少有关，但复苏策略之间的pH、血尿素氮和血清肌酐值没有差异。
结论
RSV复苏可显著恢复失血性休克后的肾线粒体功能并减少氧化损伤。
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