鳖甲煎口服液对肝纤维化大鼠AngⅡ、Ang（1－7）的影响

摘要

[目的]研究鳖甲煎口服液（biejiajian oral liquid, BOL）对肝纤维化大鼠肝组织血管紧张素Ⅱ（angiotensinⅡ，AngⅡ）、血管紧张素(1－7)[an－giotensin(1－7)，Ang(1－7)]水平及两者比值的影响。[方法]将健康雄性Wistar大鼠随机分为空白组，模型组，BOL高、低剂量组，每组10只。模型组大鼠腹腔注射未灭活猪血清，每只0．5mL，每周2次，持续8周。其余各组大鼠腹腔注射同等剂量同周期生理盐水。模型成功后，BOL低剂量组大鼠给予BOL 10g·kg－1，BOL高剂量组大鼠给予BOL 20g·kg－1，空白组与模型组大鼠每日给予等量蒸馏水，连续灌胃给药5周。计算肝、脾指数，将肝组织进行HE及Masson染色，连续监测法测定血清丙氨酸氨基转移酶（alanine aminotransferase, ALT）、天门冬氨酸氨基转移酶（aspartate aminotrans－ferase, AST）水平，放射免疫法测定血清细胞外基质成分含量，酶联免疫法测定肝组织AngⅡ、Ang(1－7)水平。[结果]与空白组比较，模型组肝脏胶原纤维增生、结构破坏，ALT、AST水平显著升高，细胞外基质成分含量均上升，AngⅡ、Ang(1－7)水平升高，AngⅡ/Ang(1－7)比值上调。BOL干预组与模型组比较，肝组织病理变化好转，血清ALT、AST、细胞外基质成分、AngⅡ水平均显著降低，Ang(1－7)水平进一步上升，AngⅡ/Ang(1－7)比值显著下降。[结论]BOL具有保护肝细胞，维护肝功能，抗肝纤维化的作用，其作用机制可能与上调Ang(1－7)水平、降低AngⅡ的水平及AngⅡ/Ang(1－7)比值有关。%Objective] To explore the effect of Biejiajian oral Liquid (BOL) on the level of angiotensinⅡ(AngⅡ) and angiotensin(1-7) [Ang(1-7)],and ratio of AngⅡ/Ang(1-7) in liver fibrosis rats. [Methods] Randomly divide male Wistar rats into blank group, model group, BOL groups of high dose and low dose, 10 in each. The model rats were injected with inactivated pig serum abdominally, 0.5mL for each, 2 times/w, for successive 8w. Other rats were injected with the same dosage and period of normal saline. After modeling, administer BOL 10g·kg-1 to low-dose groups rats, and 20g·kg-1 to high-dose group rats; give equal distilled water to blank and model groups, for successive 5 weeks of intragastric administration. The liver histopathology was examined by hematoxylin-eosin(HE) and Masson trichrome staining. Liver and spleen index were calculated. Levels of alanine transaminase(ALT) and aspartate aminotransferase(AST) in serum were assayed by automatic biochemistry detection instrument. Contents of hyaluronic acid(HA), laminin(LN), typeⅢprocollagen(PcⅢ) and type IV collagen(Ⅳ.C) in serum were detected by radioimmunoassay. AngⅡand Ang(1-7) levels were determined by enzyme linked immunosorbent assay. [Results] Compared with model group, the histological injury of liver in rats of BOL groups was relieved; serum levels of AST, ALT, HA, LN, PCⅢ and Ⅳ.C, and the content of AngⅡ in liver homogenate were decreased significantly than that of the model group. Ang(1-7) level was further increased, AngⅡ/Ang(1-7) ratio was decreased obviously in BOL groups. [Conclusion] BOL showed the protective function for hepatic fibrosis, the mechanisms of which may be associated with improvement of Ang(1-7) level, decrease of AngⅡlevel and the ratio of AngⅡand Ang(1-7).