白芍总苷对糖尿病大鼠肝脏内质网应激的调节作用  

Effect of total glucosides of paeony on endoplasmic reticulum stress in streptozotocin-induced diabetic rats

作　　者：夏玲玲[1] 周仲松[1] 谢琴秀[1] 朱启金 

机构地区：[1]安徽医科大学第一附属医院感染病科,合肥230022

出　　处：《安徽医科大学学报》2015年第10期1451-1455,共5页Acta Universitatis Medicinalis Anhui

基　　金：安徽省自然科学基金(编号:1208085MH149)

摘　　要：目的探讨白芍总苷(TGP)对糖尿病大鼠肝脏损害的保护作用是否与抑制内质网应激(ERS)有关。方法建立链脲佐菌素(STZ)诱导的糖尿病模型,随机分为对照组、模型组、TGP(50、100、200 mg/kg)给药组。应用油红O与Masson染色对肝组织行病理检查;采用免疫组化法检测肝组织ED-1表达;采用Western blot法检测GRP78、p-Perk及p-Eif2α的表达。结果 TGP给药可降低糖尿病大鼠肝重增加及肝组织总胆固醇(TC)、三酰甘油(TG)及游离脂肪酸(FFA)水平。模型组肝细胞油红O染色评分明显高于对照组(P<0.01);TGP各给药组评分明显低于模型组(P<0.01)。Masson染色模型组肝纤维化评分明显高于对照组(P<0.01);TGP 50、100、200 mg/kg给药组评分明显低于模型组(P<0.01)。免疫组化显示模型组肝组织巨噬细胞浸润明显增加,各给药组均能抑制糖尿病肝组织巨噬细胞浸润的增加。Western blot显示糖尿病模型组肝组织GRP78、pPerk及p-Eif2α表达明显高于对照组,TGP给药组肝组织GRP78、p-Perk及p-Eif2α表达明显低于模型组。结论 TGP对糖尿病肝损害有明显保护作用,其机制可能与其抗炎、抑制ERS有关。Objective To investigate prevention of early liver injury by total glucosides of paeony （ TGP） in diabetic rats and whether its mechanism was related to the inhibition of endoplasmic reticulum stress. Methods TGP （50, 100, 200 mg/kg） was orally administered once a day for 8 weeks in STZ-induced diabetic rats. The levels of cho-lesterol, triglyceride and free fatty acid in liver tissue were determined by spetrophotometric method. Liver lesions were evaluated using oil red O and Masson staining. Expression of ED-1 was determined by immunohistochemistry and GRP78, p-Perk, p-Eif2αwere determined by Western blot analysis. Results TGP treatment in all three doses significantly reduced increased liver weight and liver lipid content in diabetic rats. Oil red O staining score in dia-betic group was significantly higher than that in the control group （ P〈0. 01 ） , TGP 50 ,100 ,200 mg/kg treatment group scores were significantly lower than those in the diabetic group （ P〈0. 01 ） . Masson staining showed hepatic fibrosis score was much higher than that in the control group （ P〈0. 01 ） , hepatic fibrosis scores in TGP 50 ,100 , 200 mg/kg treatment group were significantly lower than those in the diabetic group. Compared with the control group, immunohistochemistry showed that macrophage infiltration in the liver tissue from diabetic significantly in-creased, which was inhibited by TGP treatment in all three doses. Expressions of GRP78, p-Perk and p-Eif2αde-termined by Western blot in liver tissue of diabetic group were significantly higher than that in the control group, which also were decreased by TGP administration （50, 100, 200 mg/kg）. Conclusion Our results indicate that TGP has potential as a treatment for diabetic liver injury through attenuating liver lipid accumulation and inflamma-tion as well as ERS induced by diabetic condition.

关 键 词：糖尿病 肝脏 内质网应激 炎症 白芍总苷 

分 类 号：R587.1[医药卫生—内分泌]