大黄酸分散体对糖尿病大鼠肝损伤的抑制机制  

Inhibitory mechanism of rhein-F on liver injury in diabetic rats

作　　者：吕怀恩 王文永[1] 王蕊[1] 王鹏[1] 付静波[1] 张宝生 董晓宇 高玲焕 Lü Huaien;WANG Wenyong;WANG Rui;WANG Peng;FU Jingbo;ZHANG Baosheng;DONG Xiaoyu;GAO Linghuan(Department of Pharmacy,People′s Hospital of Tangshan Fengrun District,Tangshan 063000,China;School of Basic Medical Science,North China University of Science and Technology,Tangshan 063000,China)

机构地区：[1]唐山市丰润区人民医院药剂科,唐山063000 [2]华北理工大学基础医学院,唐山063000

出　　处：《西北药学杂志》2021年第2期243-248,共6页Northwest Pharmaceutical Journal

基　　金：河北省自然科学基金青年科学基金项目(编号:2018209260)。

摘　　要：目的比较大黄酸(rhein)与大黄酸分散体(rhein-F)对糖尿病大鼠血糖、肝组织病理改变的影响,并探讨其相关机制。方法将10周龄大鼠高脂饲料喂饲后尾静脉注射链脲佐菌素制备大鼠2型糖尿病模型,随机分为糖尿病模型(DM)组、rhein(80 mg·kg^(-1))组和rhein-F(80 mg·kg^(-1))组,将正常喂养的同周龄大鼠作为正常对照(NC)组,每组10只。灌胃给药8周,测定各组大鼠血糖、肝功能指标谷草转氨酶(AST)、谷丙转氨酶(ALT)、糖基化终产物(AGEs)和肝脏指数(LI);采用苏木精-伊红(HE)、马松(Masson)染色和透射电镜观察大鼠肝脏组织学结构变化;免疫组化和Western Blot法检测肝组织中过氧化物酶体增殖物激活受体-γ(PPAR-γ)和核因子-κB(NF-κB)蛋白表达。结果rhein组和rhein-F组均可降低空腹血糖(FBG)和餐后血糖(PBG),尤其是rhein-F组对餐后1 h血糖的降低效果更明显;rhein组和rhein-F组均可不同程度地降低LI和血清AST、ALT、AGEs含量,rhein-F组降低AST和AGEs作用更明显;光镜和电镜观察结果显示,rhein-F减轻糖尿病大鼠肝组织病理损伤、超微结构的改变和胶原增生等作用强于rhein;rhein组和rhein-F组均能上调PPAR-γ和下调NF-κB蛋白表达,rhein-F作用强于rhein。结论rhein-F可降低血糖,抑制高糖所致的肝损伤,同等剂量下优于rhein,其机制可能与降低血糖、抑制AGEs产生及上调PPAR-γ和下调NF-κB蛋白表达有关。Objective To compare the effects of rhein and rhein-F on blood glucose and pathological changes in the liver tissues of diabetic rats,and discuss the relevant mechanism.Methods The model of type 2 diabetes rats was established by using high-fat feed and streptozocin.These rats were randomly divided into the diabetes model(DM)group,rhein(80 mg·kg^(-1))group and rhein-F(80 mg·kg^(-1))group,10 rats in each group.And 10 rats were fed normally as the normal control(NC)group.The fasting and postprandial blood glucose,liver function indexes(serum aspartate transaminase(AST),alanine aminotransferase(ALT),advanced glycation end products(AGEs)and liver weight index(LI)were measured in each group of rats after intragastric admini-stration for 8 weeks.In addition,the histological structure changes liver tissues in rats were observed under a light microscope after the HE staining and Masson′s trichrome staining,and the ultrastructural changes were observed under a transmission electron microscope.Moreover,the expression level of peroxisome proliferatoractivated receptorγ(PPAR-γ)and nuclear factorκB(NF-κB)was detected by immunohistochemistry and Western Blot.Results Both rhein and rhein-F groups reduced the level of fasting and postprandial blood glucose,and rhein-F group had a more significant effect on reducing postprandial blood glucose,especially the postprandial blood glucose 1 h after meal.rhein group and rhein-F group decreased the LI and the content of AST,ALT and AGEs in serum with different degrees,and rhein-F group had a more significant effect on reducing AST and AGEs.rhein-F had a stronger effect than rhein on reducing the pathological injury,ultrastructural changes and collagen hyperplasia in the liver tissues of diabetic rats.Both rhein and rhein-F groups increase PPAR-γprotein expression level and decrease NF-κB protein expression level,rhein-F has a more obvious effect.Conclusion rhein-F can reduce blood glucose and have a protective effect on diabetic liver,and rhein-F has a better effect than rhein

关 键 词：大黄酸 大黄酸分散体 糖尿病 肝损伤 病理改变 

分 类 号：R965[医药卫生—药理学]