Olteanu Diana, Filip A, Mureşan A, Nagy A, Tabaran F, Moldovan R, Decea N, Catoi C, Clichici S
University of Medicine and Pharmacy Iuliu Haţieganu Department of Physiology Cluj Napoca Romania.
Acta Physiol Hung. 2012 Mar;99(1):61-73. doi: 10.1556/APhysiol.99.2012.1.7.
Inflammation and oxidative stress are important pathways in the development of liver fibrosis following biliary obstruction.
To evaluate the effects of low dose dexamethasone and chitosan, a natural compound with no side-effects, on liver damage caused by bile duct ligation in rats.
Fifty female Wistar rats, randomly and equally divided in 5 groups: I (SHAM) underwent only laparotomy, II (BDL) with bile duct ligation, III (DEX) 0.125 mg/kg dexamethasone i.m. daily, IV (CS) 1 mg/kg chitosan by gavage and group V (DEX+CS), both substances. After six days, the following parameters were assessed from liver homogenates: malondialdehyde (MDA), protein carbonyls (PC), reduced glutathione (GSH), total SH groupings, nitric oxide (NO), and from plasma: MDA, γ-glutamyltranspeptidase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TB). A histopathological examination was performed using some of the elements of the Knodell Histological Activity Index.
BDL significantly increases the levels of MDA, liver enzymes, and the necro-inflammatory score compared to the sham group and it decreases the antioxidant capacity. DEX protects against lipid peroxidation and improves the antioxidant capacity, but it is not able to protect the hepatocytes. Chitosan significantly decreases (p<0.05) the levels of MDA (0.07±0.01 vs 0.10±0.01 nmoles/mg protein BDL group, p=0.027) and also ALT, TB, GGT and reduces liver necrosis and inflammation (2.75±0.95 vs 1±0, p<0.05). Both CS and DEX reduce the level of NO significantly.
BDL induces severe oxidative stress damage after six days already. Chitosan proved very efficient in protecting the hepatocytes against oxidative stress, a fact supported by the histological findings.
炎症和氧化应激是胆管梗阻后肝纤维化发展的重要途径。
评估低剂量地塞米松和壳聚糖（一种无副作用的天然化合物）对大鼠胆管结扎所致肝损伤的影响。
50只雌性Wistar大鼠随机等分为5组：I组（假手术组）仅行剖腹术；II组（胆管结扎组）行胆管结扎；III组（地塞米松组）每日肌肉注射0.125mg/kg地塞米松；IV组（壳聚糖组）经口灌胃1mg/kg壳聚糖；V组（地塞米松+壳聚糖组）给予两种物质。6天后，从肝匀浆中评估以下参数：丙二醛（MDA）、蛋白质羰基（PC）、还原型谷胱甘肽（GSH）、总巯基基团、一氧化氮（NO），并从血浆中评估：MDA、γ-谷氨酰转肽酶（GGT）、丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）和总胆红素（TB）。使用Knodell组织学活性指数的一些指标进行组织病理学检查。
与假手术组相比，胆管结扎组显著增加了MDA、肝酶水平和坏死性炎症评分，并降低了抗氧化能力。地塞米松可防止脂质过氧化并提高抗氧化能力，但不能保护肝细胞。壳聚糖显著降低（p<0.05）MDA水平（0.07±0.01对胆管结扎组0.10±0.01nmol/mg蛋白质，p=0.027），还降低了ALT、TB、GGT水平，并减轻了肝坏死和炎症（2.75±0.95对1±0，p<0.05）。壳聚糖和地塞米松均显著降低NO水平。
胆管结扎6天后即诱导严重的氧化应激损伤。壳聚糖在保护肝细胞免受氧化应激方面被证明非常有效，这一事实得到了组织学结果的支持。
