摘要
目的探讨不同时间给予二至丸对衰老性肝损伤的影响及可能作用机制。方法60只C57雄性小鼠随机分为正常对照组、模型组、二至丸1:00组、二至丸7:00组、二至丸13:00组、二至丸19:00组,每组10只。除正常对照组外其余各组小鼠每日皮下注射300 mg/kg D-半乳糖诱导衰老性肝损伤模型,共56天。于造模第11天开始,二至丸1:00组、二至丸7:00组、二至丸13:00组、二至丸19:00组分别于1:00、7:00、13:00和19:00给予二至丸2.5 g/kg灌胃,正常对照组和模型组小鼠灌胃给予0.01 ml/g生理盐水,连续46天。检测血清中丙氨酸氨基转移酶(ALT)、门冬氨酸氨基转移酶(AST)和过氧化氢酶(CAT)、超氧化物歧化酶(SOD)、丙二醛(MDA)水平;HE染色观察肝组织病理形态变化,Western blot检测小鼠肝组织生物钟相关因子脑和肌肉芳香烃受体核转运样蛋白1(Bmal1)和隐花色素1(Cry1)蛋白表达水平。结果与正常对照组相比,模型组小鼠肝组织出现广泛水肿样变,细胞核固缩深染,肝索排列紊乱等,血清ALT、AST、MDA水平显著升高,血清SOD、CAT及肝组织Bmal1、Cry1蛋白水平显著降低(P<0.01);与模型组相比,二至丸1:00组和二至丸7:00组小鼠肝组织病理学变化均有明显的改善,血清中的ALT、AST、MDA水平显著降低,血清SOD、CAT及肝组织Bmal1、Cry1蛋白水平显著降低(P<0.05或P<0.01),二至丸13:00组和二至丸19:00组小鼠肝组织则表现出严重的病理性损伤,血清ALT、AST、SOD、CAT和MDA水平,肝组织Cry1蛋白水平差异无统计学意义(P>0.05),二至丸19:00组小鼠肝组织Bmal1蛋白水平明显升高(P<0.05);与二至丸1:00组比较,二至丸7:00组小鼠血清ALT和AST水平显著升高,肝组织Bmal1、Cry1蛋白水平,二至丸19:00组肝组织Bmal1蛋白水平均明显降低(P<0.01)。结论二至丸对D-半乳糖诱导的小鼠衰老性肝损伤具有显著的保护作用,且其药理作用具有明显的时间差异性,其中于1:00给予二至丸的改
Objective To explore the effect and related mechanism of Erzhi Pill(二至丸)given at different times on the liver injury of aging mice.Methods Sixty C57 male mice were randomly divided into normal control group,model group and four Erzhi Pill groups of 1:00,7:00,13:00 and 19:00,with ten mice in each group.Ex‐cept for the normal control group,mice were given subcutaneous injected of D-galactose(D-gal)at a dose of 300 mg·kg^(-1)·d^(-1)for 56 consecutive days to establish the aging liver injury model.The Erzhi Pill groups were given 2.5 g·kg^(-1)Erzhi pill at different time(1:00,7:00,13:00,19:00)from the 11th day of modelling and lasted for 46 days.Mean‐while,the mice in the normal control group and model group were given 0.01 ml·g^(-1)of normal saline by gavage.The serum levels of alanine transaminase(ALT),aspartate aminotransferase(AST),catalase(CAT),superoxide dis‐mutase(SOD),and malonic dialdehyde(MDA)were detected.The HE staining was used to assess the pathological changes of liver tissue.The protein expression of Bmal1 and Cry1 in liver were detected by Western blot.Results Compared to those in the normal control group,the liver tissue of the mice in the model group showed extensive ede‐ma-like changes,nuclear pyknosis and deep staining,and disorderly arranged hepatic cords;the serum levels of ALT,AST and MDA in the model group increased significantly(P<0.01),while serum SOD and CAT levels de‐creased,as well as the protein expression of Bmal1 and Cry1 in the liver tissue(P<0.01).Compared to those in the model group,the liver histopathological changes were significantly improved in the Erzhi Pill 1:00 group and 7:00 group,with significantly decreased ALT,AST and MDA levels and increased SOD,CAT levels and protein expres‐sion of Bmal1 and Cry1(P<0.05 or P<0.01);there were severe pathological damage in the liver tissue in the Erzhi Pill 13:00 group 19:00 group,both having no significant differences in serum ALT,AST,SOD,CAT and MDA lev‐els and Cry1 protein expression compared to the model group
作者
马湘宇
宫宇晴
卫心怡
冯梦林
李三强
段冷昕
MA Xiangyu;GONG Yuqing;WEI Xinyi;FENG Menglin;LI Sanqiang;DUAN Lengxin(School of Basic Medicine,Henan University of Science and Technology,Luoyang,471000)
出处
《中医杂志》
CSCD
北大核心
2023年第4期387-392,共6页
Journal of Traditional Chinese Medicine
基金
国家自然科学基金(82170606)
河南省科技攻关计划(21A360001)。
关键词
衰老
肝损伤
二至丸
生物钟
氧化应激
aging
liver injury
Erzhi Pill(二至丸)
biological clock
oxidative stress
