Dibazar F, Hajipour B, Hosseinian M M, Hemmati M R, Ghandiha A
Department of Anatomy and Histology, Islamic Azad University, Tabriz, Iran.
Folia Morphol (Warsz). 2008 Nov;67(4):231-5.
Liver failure is still a significant clinical problem after transplantation surgery, tissue resections (the Pringle manoeuvre) and haemorrhagic shock. The restoration of blood flow to an ischaemic region leads to tissue injury at a greater rate than the original ischaemic insult, an event termed "ischaemia-reperfusion injury" (I/R). Despite advances in surgical techniques, I/R still poses a problem of clinical importance. In this research, we studied the effect of simvastatin pretreatment on liver and lung injury induced by hepatic I/R. Rats were subjected to 30 min of ischaemia followed by 24 h of reperfusion. Simvastatin (10 mg/kg) was administered orally from three days before the operation. After the reperfusion time, serum ALT, AST, LDH and TNF a levels were studied and liver and lung tissues were stained with haematoxylin and eosin and TUNEL to detect apoptotic cells. Serum aminotransferase activity and LDH and TNFalpha levels were increased markedly by hepatic I/R, and these were suppressed significantly by simvastatin. The tissue injury index and the number of apoptotic cells via TUNEL staining in the liver and lungs were higher in the I/R group than in the I/R + simvastatin group. These results suggest that simvastatin ameliorates I/R-induced liver and lung tissue damage by inhibiting the level of inflammation and the apoptotic pathways. Simvastatin administration may therefore provide protection against the adverse effects of I/R injury in liver transplantation.
肝移植手术、组织切除（普林格尔手法）及失血性休克后，肝衰竭仍是一个严重的临床问题。缺血区域血流的恢复导致组织损伤的速度比最初的缺血损伤更快，这一现象被称为“缺血再灌注损伤”（I/R）。尽管手术技术有所进步，但I/R仍然是一个具有临床重要性的问题。在本研究中，我们研究了辛伐他汀预处理对肝缺血再灌注诱导的肝和肺损伤的影响。大鼠经历30分钟的缺血，随后进行24小时的再灌注。从手术前三天开始口服给予辛伐他汀（10毫克/千克）。再灌注期结束后，检测血清谷丙转氨酶（ALT）、谷草转氨酶（AST）、乳酸脱氢酶（LDH）和肿瘤坏死因子α（TNFα）水平，并对肝和肺组织进行苏木精-伊红染色及TUNEL染色以检测凋亡细胞。肝缺血再灌注显著提高了血清转氨酶活性、LDH及TNFα水平，而辛伐他汀可显著抑制这些指标。I/R组肝和肺组织损伤指数及TUNEL染色凋亡细胞数量高于I/R+辛伐他汀组。这些结果表明，辛伐他汀通过抑制炎症水平和凋亡途径改善缺血再灌注诱导的肝和肺组织损伤。因此，给予辛伐他汀可能为肝移植中缺血再灌注损伤的不良反应提供保护。
