银杏内酯B对脂肪肝小鼠肝脏缺血再灌注损伤的影响及其机制
Effect of ginkgolide B on hepatic ischemia-reperfusion injury in mice with fatty liver disease and its mechanism
黄希健 1赵金鑫 2罗礼键 3刘欢 1蔡金贞4
作者信息
- 1. 青岛大学附属医院器官移植中心,山东青岛 266035
- 2. 宁波大学附属第一医院肝胆胰外科
- 3. 福建医科大学附属协和医院
- 4. 青岛大学附属医院器官移植中心,山东青岛 266035;福建医科大学附属协和医院
- 折叠
摘要
目的 探究银杏内酯B对脂肪肝小鼠肝脏缺血再灌注损伤的影响及其机制.方法 选择60％高脂饲料喂养16周的C57BL/6J雄性小鼠共25只,分为假手术组(开腹后缝合)、模型组(阻断肝中、左叶血流1 h后再灌注6 h)、银杏内酯B组(25 mg/kg银杏内酯B腹腔注射2次后同模型组处理)、GW9662组(1 mg/kg GW9662腹腔注射2次后同模型组处理)、GW9662+银杏内酯B组(25 mg/kg银杏内酯B+l mg/kg GW9662混合溶液腹腔注射2次后同模型组处理).给药并行手术后6 h检测各组小鼠血清谷丙转氨酶(ALT)、谷草转氨酶(AST)水平,免疫印迹法检测各组小鼠肝组织Bax、Bcl-2、PPARγ蛋白表达水平,油红O染色检测各组小鼠肝脏组织脂肪化程度,HE染色检测各组小鼠肝脏组织坏死程度.结果 油红O染色结果显示,各组小鼠肝脏脂肪化程度已达脂肪肝水平.血清酶学检测结果显示,银杏内酯B组、GW9662+银杏内酯B组小鼠血清ALT、AST水平均显著低于模型组(P＜0.05),银杏内酯B组小鼠血清ALT水平显著低于GW9662+银杏内酯B组(P＜0.05).HE染色结果显示,银杏内酯B组小鼠肝组织坏死面积百分比显著低于模型组及GW9662+银杏内酯B组(P＜0.05).免疫印迹结果显示,银杏内酯B组小鼠肝组织Bax表达水平显著低于模型组(P＜0.05),而Bcl-2、PPARy表达水平显著高于模型组及GW9662+银杏内酯B组(P＜0.05).结论 银杏内酯B可通过上调肝组织PPARy水平以减轻脂肪肝小鼠缺血再灌注损伤.
Abstract
Objective To investigate the effect of ginkgolide B on hepatic ischemia-reperfusion injury in mice with fatty liver disease and its mechanism.Methods A total of 25 male C57BL/6J mice were fed with 60％high-fat diet for 16 weeks,and then they were divided into sham-operation group(laparotomy and suture),model group(occlusion of blood flow in the middle and left lobes of the liver for 1 h,followed by reperfusion for 6 h),ginkgolide B group(intraperitoneal injection of 25 mg/kg ginkgolide B twice,followed by the treatment in the model group),GW9662 group(intraperitoneal injection of 1 mg/kg GW9662 twice,fol-lowed by the treatment in the model group),and GW9662+ginkgolide B group(intraperitoneal injection of 25 mg/kg ginkgolide B+l mg/kg GW9662 twice,followed by the treatment in the model group).At 6 h after administration and surgery,the serum levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)were measured for each group;Western blotting was used to measure the protein expression levels of Bax,Bcl-2,and PPARγ in liver tissue;oil red O staining was used to measure the degree of fatty changes in the liver,and HE staining was used to measure the degree of necrosis in liver tissue.Results Oil red O staining showed that the degree of fatty changes in the liver had reached the level of fatty liver disease in each group.The se-rum enzymatic analysis showed that the ginkgolide B group and the GW9662+ginkgolide B group had significantly lower serum le-vels of ALT and AST than the model group(P＜0.05),and the ginkgolide B group had a significantly lower serum level of ALT than the GW9662+ginkgolide B group(P＜0.05).HE staining showed that the ginkgolide B group had a significantly lower per-centage of necrotic area in liver tissue than the model group and the GW9662+ginkgolide B group(P＜0.05).Western blotting showed that the ginkgolide B group had a significantly lower expression level of Bax in liver tissue than the model group(P＜0.05),as well as significantly higher expression levels of Bcl-2 and PPARy than the model group and the GW9662+ginkgolide B group(P＜0.05).Conclusion Ginkgolide B can alleviate ischemia-reperfusion injury in mice with fatty liver disease by upregu-lating PPARγ in liver tissue.
关键词
再灌注损伤/脂肪肝/银杏内酯类/PPARγ/疾病模型,动物Key words
Reperfusion injury/Fatty liver/Bilobalides/PPAR gamma/Disease models,animal引用本文复制引用
基金项目
国家自然科学基金项目(82370666)
福建省自然科学基金项目(ZR202111260267)
出版年
2024
国家科技期刊平台
NSTL
万方数据