黄芪甲苷预处理对小鼠肝脏缺血再灌注损伤的保护作用

Protection of astragaloside Ⅳ pretreatment against liver ischemia/reperfusion injury in mice

目的探讨黄芪甲苷（astragaloside Ⅳ）预处理对小鼠肝脏缺血再灌注损伤的保护作用及其机制。方法将60只雄性C57BL／6小鼠分为4组，15只／组，A组：假手术对照组，B组：假手术黄芪甲苷组，C组：实验对照组，D组：黄芪甲苷实验组。黄芪甲苷组每只腹腔注射黄芪甲苷24mg·kg^-1·d^-1，对照组每天腹腔注射等体积无菌生理盐水，共1周。建立小鼠肝脏部分缺血再灌注损伤模型，复流24h后采集标本，测定血清中转氨酶ALT和AST水平，光镜下观察H＆E染色肝组织病理学变化，酶联免疫吸附试验（ELISA）检测血清中IL-1β，IL-6，TNF-α的含量，采用Western blot技术检测小鼠肝脏组织中核因子-κB（NF-κB）的表达。结果黄芪甲苷实验组ALT及AST较实验对照组明显降低[AST：C组（4290±292）U／L vs．D组（2373±416）U／L，t=0．844；ALT：C组（4146±500）U／L vs．D组（2318±289）U／L，t=7．08，均P〈0．05]，组织学损伤也明显减轻；ELISA结果显示，黄芪甲苷预处理能明显降低外周IL-1β，IL-6，TNF-α的含量（IL-1β：t=10．04；IL-6：t=6．281；TNF-α：t=6．817；均P〈0．05）。黄芪甲苷实验组肝脏组织中NF—κB表达量明显低于实验对照组。结论黄芪甲苷预处理对小鼠肝脏缺血再灌注损伤有明显的保护作用。

Objective To investigate the protective effect of astragaloside Ⅳ pretreatment against liver ischemia/reperfusion （I/R） injury in mice. Methods Sixty male C57BL/6 mice were randomized into four groups （15 mice in each group）： group A： sham surgery with saline injection, group B： sham surgery with astragaloside Ⅳ injection, group C： I/R group with saline injection, group D： I/R and astragaloside Ⅳ injection. Mice were pretreated by daily intraperitoneal injection of saline or astragaloside IV （24 mg · kg^-1 · d^-1 ） for one week. The mouse partial liver model of I/R injury was established, and samples were collected at the 24 h after the I/R injury. Serum ALT and AST levels were determined, the histologic changes were observed by H＆E staining under the light microscopy, whereas the nuclear factor （NF）-κB was assessed with Western blotting. Serum IL-1β, IL-6, and TNF-α levels were measured by enzyme-linked immunosorbent assay （ELISA）. Results Serum ALT and AST levels significantly decreased and the histological damage was significantly alleviated in astragaloside Ⅳ treated I/R group as compared with saline I/R group [AST： C： （4290 ±292） U/L vs. D： （2373 ±416） U/L t =0. 844;ALT： C： （4146 ±500） U/L vs. D：（2318 ±289） U/L t =7.08 P 〈0.05]. In comparison with group 3, astragaloside Ⅳ reduced NF-κB nuclear expression. ELISA showed astragaloside Ⅳ significantly inhibit the levels of IL-1β, IL-6, and TNF-α in the serum （ IL-1β： t = 10. 04; IL-6： t = 6. 281; TNF-α： t = 6. 817; P 〈 O. 05 ）. Conclusions Pretreatment with astragaloside Ⅳ effectively protect against liver ischemia/reperfusion injury in mice.