Lee Sang, Kim Sendia, Le Hau D, Meisel Jonathan, Strijbosch Robbert A M, Nose Vania, Puder Mark
Department of Surgery, The Vascular Biology Program, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA.
J Pediatr Surg. 2008 Nov;43(11):2010-5. doi: 10.1016/j.jpedsurg.2008.05.030.
Bile duct obstruction and subsequent cholestasis produces hepatocellular injury and an inflammatory response. Fatty acid constitution of cell membranes plays a major role in the inflammatory cascade. Omega-3 fatty acids are antiinflammatory. We proposed that omega-3 fatty acid supplementation would reduce hepatocellular damage and cell death in a model of murine common bile duct ligation.
Mice underwent bile duct ligation and were administered either control soy diet (omega-6) or Menhaden diet (omega-3), and parameters of liver injury were measured at postoperative days 1, 4, and 8. Serum was analyzed for liver function tests. Liver tissue was scored for histologic necrosis and inflammation, and apoptosis was qualitatively measured.
At day 8, comparing control and Menhaden, liver function tests were not significantly different. The H&E slides were analyzed and scored. At day 4, the mean necrosis scores for the Menhaden-fed group was 0.01 +/- 0.028 and 0.46 +/- 0.108 for the soy-fed group (P = .001) and at day 8, 0.420 +/- 0.107 and 1.22 +/- 0.132 (P < .001). The mean portal inflammation score for day 4 Menhaden-fed and soy-fed mice was 1.40 +/- 0.245 for both groups (P = 1.00) and for day 8, 1.80 +/- 0.200 and 2.80 +/- 0.200 (P = .008). At day 1, the median terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling scores of the Menhaden vs soy group were 6.0 and 0.0 (P < .001); day 4, 24.0 and 3.0 (P < .001); and day 8, 0.0 and 3.0 (P < .001), respectively.
Although there appears to be a trend toward biochemical protection and a marked reduction of necrosis and inflammation, there was no significant liver function test difference between control and Menhaden groups. Considering our data of blunted histologic hepatotoxicity with omega-3 fatty acid supplementation, we hypothesize that this may be a method of reducing long-term complications of liver injury secondary to diseases of cholestasis such as biliary atresia, namely fibrosis and cirrhosis.
胆管梗阻及随后的胆汁淤积会导致肝细胞损伤和炎症反应。细胞膜的脂肪酸组成在炎症级联反应中起主要作用。ω-3脂肪酸具有抗炎作用。我们提出，在小鼠胆总管结扎模型中补充ω-3脂肪酸可减少肝细胞损伤和细胞死亡。
对小鼠进行胆管结扎，并给予对照大豆饮食（ω-6）或鲱鱼油饮食（ω-3），在术后第1、4和8天测量肝损伤参数。分析血清进行肝功能测试。对肝组织进行组织学坏死和炎症评分，并定性测量细胞凋亡。
在第8天，比较对照组和鲱鱼油组，肝功能测试无显著差异。对苏木精-伊红染色切片进行分析和评分。在第4天，鲱鱼油喂养组的平均坏死评分为0.01±0.028，大豆喂养组为0.46±0.108（P = 0.001）；在第8天，分别为0.420±0.107和1.22±0.132（P < 0.001）。第4天鲱鱼油喂养和大豆喂养小鼠的平均门静脉炎症评分为1.40±0.245（P = 1.00）；在第8天，分别为1.80±0.200和2.80±0.200（P = 0.008）。在第1天，鲱鱼油组与大豆组的末端脱氧核苷酸转移酶生物素-dUTP缺口末端标记评分中位数分别为6.0和0.0（P < 0.001）；第4天，分别为24.0和3.0（P < 0.001）；第8天，分别为0.0和3.0（P < 0.001）。
虽然似乎存在生化保护趋势，坏死和炎症明显减少，但对照组和鲱鱼油组之间的肝功能测试无显著差异。考虑到我们补充ω-3脂肪酸后组织学肝毒性减弱的数据，我们推测这可能是一种减少胆汁淤积性疾病（如胆道闭锁）继发肝损伤长期并发症（即纤维化和肝硬化）的方法。
