Veteläinen Reeta, van Vliet Arlène K, van Gulik Thomas M
Department of Surgery, Surgical Laboratory, Academic Medical Center, Amsterdam, The Netherlands.
Ann Surg. 2007 Jan;245(1):44-50. doi: 10.1097/01.sla.0000225253.84501.0e.
The aim of this study was to assess the influence of severe steatosis with inflammation on hepatocellular recovery after 70% hepatectomy in a rat model of diet-induced steatosis.
Patients with steatosis have an increased risk of inflammatory complications after liver resection. This might be attributable to Kupffer cell-mediated inflammation in steatotic livers causing progressive injury.
Male Wistar rats were fed a standard methionine- and choline-deficient diet for 1 or 5 weeks. A 70% partial hepatectomy (PH) was performed, after which rats were killed at 24, 48, or 72 hours. The extent of steatosis and inflammation was determined by assessment of hepatic triglycerides, cytokine content, and histopathology. Outcome parameters were: liver regeneration (MIB-5 proliferation rate, mitotic index, and regenerating liver mass), hepatocellular injury (plasma aminotransferases, lipid peroxidation, histopathology, and apoptosis), Kupffer cell-mediated proinflammatory response (TNF-alpha, IL-1beta, IL-6, IL-10 in plasma and liver) and antioxidant content (total glutathione).
Methionine- and choline-deficient diet induced uncomplicated steatosis after 1 week (<30% hepatocytes affected without inflammation) and severe steatosis after 5 weeks (>60% hepatocytes affected, including prominent inflammation) as confirmed by histopathology. After PH, liver regeneration was impaired at all time points in the severe steatosis group as compared with the mild and control groups (P < 0.05). Hepatocellular injury was significantly increased in the severe steatosis group at all time points (P < 0.05). Kupffer cell-mediated inflammatory responses were aggravated in the severe steatosis group along with decreased antioxidant content (P < 0.05). Necrosis was the main type of cell death in severe steatotic livers compared with mainly apoptotic cell death in mild steatotic and normal livers.
Steatosis with prominent inflammation impaired liver regeneration probably because of increased hepatocellular lipid peroxidation and damage in concert with Kupffer cell-mediated proinflammatory responses. These results suggest an increased risk of performing extensive liver resection in the presence of severe steatosis.
本研究旨在评估在饮食诱导性脂肪变性大鼠模型中，伴有炎症的严重脂肪变性对70%肝切除术后肝细胞恢复的影响。
脂肪变性患者肝切除术后发生炎症并发症的风险增加。这可能归因于枯否细胞介导的脂肪变性肝脏炎症导致的进行性损伤。
雄性Wistar大鼠喂食标准蛋氨酸和胆碱缺乏饮食1周或5周。进行70%部分肝切除术（PH），术后在24、48或72小时处死大鼠。通过评估肝甘油三酯、细胞因子含量和组织病理学来确定脂肪变性和炎症的程度。结果参数包括：肝再生（MIB-5增殖率、有丝分裂指数和再生肝质量）、肝细胞损伤（血浆氨基转移酶、脂质过氧化、组织病理学和凋亡）、枯否细胞介导的促炎反应（血浆和肝脏中的TNF-α、IL-1β、IL-6、IL-10）和抗氧化剂含量（总谷胱甘肽）。
组织病理学证实，蛋氨酸和胆碱缺乏饮食在1周后诱导出无并发症的脂肪变性（<30%肝细胞受影响且无炎症），5周后诱导出严重脂肪变性（>60%肝细胞受影响，包括明显炎症）。PH术后，与轻度和对照组相比，严重脂肪变性组在所有时间点的肝再生均受损（P<0.05）。严重脂肪变性组在所有时间点的肝细胞损伤均显著增加（P<0.05）。严重脂肪变性组枯否细胞介导的炎症反应加剧，同时抗氧化剂含量降低（P<0.05）。与轻度脂肪变性和正常肝脏主要为凋亡性细胞死亡相比，严重脂肪变性肝脏中坏死是主要的细胞死亡类型。
伴有明显炎症的脂肪变性损害肝再生，可能是由于肝细胞脂质过氧化增加和损伤，以及枯否细胞介导的促炎反应共同作用的结果。这些结果表明，在存在严重脂肪变性的情况下进行广泛肝切除术的风险增加。
