Division of Nephrology, West China Hospital of Sichuan University, Chengdu 610041, China.
Artif Organs. 2013 Apr;37(4):390-400. doi: 10.1111/j.1525-1594.2012.01574.x. Epub 2013 Feb 27.
Rhabdomyolysis (RM) and subsequent myoglobin (Mb) deposition can lead to acute kidney injury. Continuous venovenous hemofiltration (CVVH) can remove Mb, but direct renal protection is unclear. We hypothesized that CVVH can improve renal mitochondrial dysfunction in its early stage. Twenty-four mongrel dogs were randomly divided into four groups: (A) control; (B) model; (C) model + CVVH (50 mL/kg/h); and (D) model + CVVH (30 mL/kg/h). RM was induced by glycerol via intramuscular injection. The dogs were closely monitored for urine flow and renal function. Mb, plasma tumor necrosis factor-α (TNF-α), and interleukin (IL)-6 were measured by enzyme-linked immunosorbent assay. After 8 h of CVVH, the morphological changes of renal mitochondria were observed and mitochondrial function indicators (reactive oxygen species, malondialdehyde, and respiratory control index) were detected. Western blot analysis was used to detect the expression of Mb, TNF-α, and IL-6 in renal tubules. The terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay method and Western blot analysis were used to detect apoptosis and apoptosis-related proteins. In group B, the dog urine output gradually decreased with increased blood creatinine. In groups C and D, the urine output was normal and stable. CVVH effectively eliminated Mb. High-dose CVVH was significantly better for removal efficiency than low-dose CVVH. CVVH significantly reduced the deposition of circulating Mb in the kidney in a dose-dependent manner. The impact of CVVH on TNF-α and IL-6 were not observed. The morphological changes of mitochondria and function indicators were significantly improved in group C compared with groups D and B. Compared with group B, renal apoptosis and apoptosis-related protein expression were inhibited in groups C and D. Group C was significantly better for mitochondrial improvement and apoptosis inhibition than group D. At the cellular and molecular level, CVVH can improve renal mitochondrial function and inhibit cell apoptosis. Early CVVH can protect from RM-caused renal injuries in a dose-dependent manner.
横纹肌溶解症（RM）和随后的肌红蛋白（Mb）沉积可导致急性肾损伤。连续静脉-静脉血液滤过（CVVH）可以清除 Mb，但直接的肾脏保护作用尚不清楚。我们假设 CVVH 可以在早期改善肾脏线粒体功能障碍。24 只杂种狗被随机分为四组：（A）对照组；（B）模型组；（C）模型+CVVH（50ml/kg/h）；和（D）模型+CVVH（30ml/kg/h）。通过肌肉内注射甘油诱导 RM。密切监测狗的尿量和肾功能。通过酶联免疫吸附试验测定 Mb、血浆肿瘤坏死因子-α（TNF-α）和白细胞介素（IL）-6。CVVH 8 小时后，观察肾线粒体的形态变化，并检测线粒体功能指标（活性氧、丙二醛和呼吸控制指数）。Western blot 分析用于检测肾小管中 Mb、TNF-α和 IL-6的表达。末端脱氧核苷酸转移酶介导的 dUTP-生物素缺口末端标记法和 Western blot 分析用于检测细胞凋亡和凋亡相关蛋白。在 B 组中，狗的尿量逐渐减少，血肌酐增加。在 C 组和 D 组，尿量正常且稳定。CVVH 有效清除 Mb。高剂量 CVVH 的清除效率明显优于低剂量 CVVH。CVVH 以剂量依赖性方式显著减少 Mb 在肾脏中的循环沉积。未观察到 CVVH 对 TNF-α和 IL-6 的影响。与 D 组和 B 组相比，C 组的线粒体形态变化和功能指标明显改善。与 B 组相比，C 组和 D 组的肾细胞凋亡和凋亡相关蛋白表达均受到抑制。与 D 组相比，C 组的线粒体改善和凋亡抑制作用更为明显。在细胞和分子水平上，CVVH 可改善肾脏线粒体功能并抑制细胞凋亡。早期 CVVH 可在一定程度上保护 RM 引起的肾脏损伤。
