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目的探讨亚砷酸钠致大鼠肝功能损伤和肝纤维化形成及其机制。方法将32只成年清洁级SD大鼠随机分为对照(普通饲料)组和低、中、高剂量亚砷酸钠(饲料中砷含量分别为25、50、100 mg/kg)染毒组,每组8只,雌雄各半。采用喂饲法进行染毒,连续染毒3个月。检测大鼠肝砷含量及血清天门冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)的活力和透明质酸(HA)、层黏连蛋白(LN)、Ⅲ型前胶原(PCⅢ)、Ⅳ型胶原(Ⅳ-C)的含量以及纤维化面积。结果与对照组比较,各剂量亚砷酸钠染毒组大鼠的肝砷含量均升高,肝脏增生纤维组织面积均增大,差异有统计学意义(P<0.05);与对照组比较,各剂量亚砷酸钠染毒组大鼠血清HA的含量和高剂量亚砷酸钠染毒组大鼠血清LN含量及高剂量亚砷酸钠染毒组雌性大鼠血清PCⅢ的含量以及中、高剂量亚砷酸钠染毒组雄性大鼠血清PCⅢ、Ⅳ-C的含量均升高,差异有统计学意义(P<0.05);与对照组比较,各剂量亚砷酸钠染毒组大鼠血清ALT、AST的活力均升高,除雌性大鼠中、低剂量组外,差异有统计学意义(P<0.05);且随着亚砷酸钠染毒剂量的升高,大鼠的肝砷含量、肝脏增生纤维组织面积及血清ALT、AST的活力和HA、LN、PCⅢ、Ⅳ-C的含量均呈上升趋势。结论亚砷酸钠饲料染毒可导致大鼠肝功能的损伤,进而发生肝纤维化。
Objective To investigate the mechanism of arsenic trioxide induced hepatic injury and hepatic fibrosis in rats. Methods Thirty-two adult SD rats were randomly divided into control (normal diet) group and low, medium and high doses of sodium arsenite (arsenic content of 25, 50, 100 mg / kg) Each group of 8, male and female half. Using feeding method for exposure, continuous exposure for 3 months. The levels of arsenic in rat liver and serum activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and the activity of hyaluronic acid (HA), laminin (LN), procollagen type Ⅲ (PC Ⅲ), type Ⅳ collagen (Ⅳ-C) content and fibrosis area. Results Compared with the control group, the arsenic levels of arsenic trioxide in rats at various doses increased, while the area of hepatic fibrosis increased, with statistical significance (P <0.05). Compared with the control group, The contents of serum HA in rats exposed to sodium arsenite and the contents of serum LN in high-dose sodium arsenite-treated rats and the serum levels of PCⅢ in female rats exposed to high doses of sodium arsenite, The contents of PCⅢ and Ⅳ-C in serum of high-dose sodium arsenite-treated rats increased significantly (P <0.05), compared with the control group, the doses of sodium arsenite The activities of ALT and AST in rat serum were increased, except for the middle and low dose groups of female rats, the difference was statistically significant (P <0.05); and with the dose of sodium arsenite increased, Liver arsenic content, liver fibrosis tissue area and serum ALT, AST vitality and HA, LN, PC Ⅲ, Ⅳ-C content showed an upward trend. Conclusion Sodium arsenite diet can lead to liver damage in rats, leading to liver fibrosis.