Department of Gastroenterology, Universidade de São Paulo, SP, Brazil.
Clinics (Sao Paulo). 2010 Jul;65(7):715-21. doi: 10.1590/S1807-59322010000700011.
Steatosis is currently the most common chronic liver disease and it can aggravate ischemia-reperfusion (IR) lesions. We hypothesized that S-nitroso-N-acetylcysteine (SNAC), an NO donor component, can ameliorate cell damage from IR injury. In this paper, we report the effect of SNAC on liver IR in rats with normal livers compared to those with steatotic livers.
Thirty-four rats were divided into five groups: I (n=8), IR in normal liver; II (n=8), IR in normal liver with SNAC; III (n=9), IR in steatotic liver; IV (n=9), IR in steatotic liver with SNAC; and V (n=10), SHAN. Liver steatosis was achieved by administration of a protein-free diet. A SNAC solution was infused intraperitoneally for one hour, beginning 30 min. after partial (70%) liver ischemia. The volume of solution infused was 1 ml/100 g body weight. The animals were sacrificed four hours after reperfusion, and the liver and lung were removed for analysis. We assessed hepatic histology, mitochondrial respiration, oxidative stress (MDA), and pulmonary myeloperoxidase.
All groups showed significant alterations compared with the group that received SHAN. The results from the steatotic SNAC group revealed a significant improvement in liver mitochondrial respiration and oxidative stress compared to the steatotic group without SNAC. No difference in myeloperoxidase was observed. Histological analysis revealed no difference between the non-steatotic groups. However, the SNAC groups showed less intraparenchymal hemorrhage than groups without SNAC (p=0.02).
This study suggests that SNAC effectively protects against IR injury in the steatotic liver but not in the normal liver.
脂肪变性是目前最常见的慢性肝病,它会加重缺血再灌注(IR)损伤。我们假设一氧化氮供体成分 S-亚硝基-N-乙酰半胱氨酸(SNAC)可以改善 IR 损伤引起的细胞损伤。在本文中,我们报告了 SNAC 对正常肝脏和脂肪变性肝脏大鼠 IR 的影响。
34 只大鼠分为五组:I(n=8),正常肝脏 IR;II(n=8),正常肝脏 SNAC+IR;III(n=9),脂肪变性肝脏 IR;IV(n=9),脂肪变性肝脏 SNAC+IR;V(n=10),SHAN。通过给予无蛋白饮食诱导肝脏脂肪变性。SNAC 溶液于部分(70%)肝缺血 30 分钟后开始腹膜内输注 1 小时,输注量为 1ml/100g 体重。再灌注后 4 小时处死动物,取出肝脏和肺进行分析。我们评估了肝组织学、线粒体呼吸、氧化应激(MDA)和肺髓过氧化物酶。
与 SHAN 组相比,所有组均有显著改变。脂肪变性 SNAC 组的肝线粒体呼吸和氧化应激明显改善,与无 SNAC 的脂肪变性组相比有显著差异。髓过氧化物酶无差异。非脂肪变性组之间的组织学分析无差异。然而,SNAC 组比无 SNAC 组的肝内出血少(p=0.02)。
本研究表明,SNAC 能有效保护脂肪变性肝脏免受 IR 损伤,但不能保护正常肝脏。