鸟苷酸二钠通过抑制Caspase 3/Bax/Bcl-2凋亡通路保护LPS/D-GalN致小鼠急性肝损伤  

Protective effects of disodium guanylate on mice with acute liver injury induced by LPS/D-GalN via inhibiting the Caspase 3/Bax/Bcl-2 signaling pathway

作　　者：金少举 郭昆鹏[2] 黄亚男[3] 李盘欣 马永超 徐松涛 丁长河 陈复生[1] JIN Shao-ju;GUO Kun-peng;HUANG Ya-nan;LI Pan-xin;MA Yong-chao;XU Song-tao;DING Chang-he;CHEN Fu-sheng(College of Food Science and Technology y Henan University of Technology,Zhengzhou,Henan 450052,China;不详)

机构地区：[1]河南工业大学粮油食品学院,河南郑州450052 [2]漯河医学高等专科学校药学系 [3]河南省南街村(集团)有限公司 [4]河南省特医食品工程技术研究中心 [5]河南省营养与健康工程技术中心

出　　处：《现代预防医学》2021年第23期4365-4369,4402,共6页Modern Preventive Medicine

基　　金：中国博士后科学基金(2016M602244);漯河医学高等专科学校创新创业发展能力提升工程(2019-LYZKYYB028);漯河医学高等专科学校博士科研基金(2014-DF-003)。

摘　　要：目的观察鸟苷酸二钠(Disodium guanylate, GMP-Na;)对脂多糖(LPS)/D-氨基半乳糖(D-GalN)致小鼠急性肝损伤致小鼠肝损伤的保护作用,并探讨其Caspase 3/Bax/Bcl-2凋亡信号通路机制。方法 60只小鼠随机分为:正常对照组、模型组、阳性对照组(联苯双酯200 mg/kg)及鸟苷酸二钠高(250 mg/kg)、中(125 mg/kg)、低(62.5 mg/kg)剂量组,每组10只。各组小鼠每天给药1次,连续14 d。末次给药后4 h,除正常对照组腹腔注射生理盐水外,其余各组小鼠均腹腔注射LPS 10μg/kg+D-GalN 700 mg/kg复制急性肝损伤模型。造模后24 h,采用比色法检测小鼠血清AST、ALT、ALP和T-BIL水平;采用生化法测定肝组织SOD、MDA及GSH-Px水平;采用ELISA法测定肝组织TNF-α、IL-1β及IL-6含量;H&E染色进行肝组织病理学观察;采用RT-PCR和western blot法检测肝组织Caspase 3、Bax和Bcl-2 mRNA和蛋白表达水平。结果与模型组比较,鸟苷酸二钠250、125 mg/kg组小鼠血清ALT、AST、ALP及T-BIL水平明显下降;肝组织SOD、GSH-Px活性升高,MDA、TNF-α、IL-1β及IL-6含量降低;肝组织病理形态学损伤显著改善;肝组织Caspase 3、Bax mRNA和蛋白表达水平下调,Bcl-2 mRNA和蛋白表达水平上调。结论鸟苷酸二钠对LPS/D-GalN致小鼠急性肝损伤肝功能具有保护作用,且可抑制其诱发的肝脏炎症反应和过氧化应激反应,其作用机制与下调Caspase 3/Bax/Bcl-2凋亡信号通路有关。Objective To observe the protective effect of disodium guanylate(Disodium guanylate, GMP-Na;) on mice with acute liver injury induced by LPS/D-GalN and its’ mechanism of the Caspase 3/Bax/Bcl-2 signaling pathway. Methods 60 mice were randomly divided into normal control group, model group, positive control group(Bifendate 200 mg/kg) and GMP-Na;high(250 mg/kg), medium(125 mg/kg) and low dose(62.5 mg/kg) group. Each group had 10 mice. The mice in each group were given corresponding drugs once a day for 14 days. 4 hours after last medication, except for normal control group, mice in other groups were given LPS 10 μg/kg and D-GalN 700 mg/kg via intraperitoneal injection to establish the animal model of acute liver injury. After 24 h, the serum levels of AST, ALT, ALP and T-BIL were detected by colorimetry. Liver tissue levels of SOD, MDA and GSH-Px were measured by biochemical method. Liver tissue contents of TNF-α, IL-1β and IL-6 were detected by ELISA. H&E staining method was used to observe the pathological changes of liver tissue. Expression levels of Caspase 3, Bax and Bcl-2 in liver tissue were analyzed by RT-PCR and western blot. Results Compared with the model group, the serum levels of ALT, AST, ALP and T-BIL in GMP-Na;250 and 125 mg/kg groups were significantly decreased. The liver tissue levels of SOD and GSH-Px were increased, whereas the levels of MDA, TNF-α, IL-1β and IL-6 were decreased, and the pathological changes of liver tissue were significantly improved. The expression levels of liver tissue Caspase 3 and Bax mRNA and protein were down-regulated, and the expression levels of Bcl-2 mRNA and protein were up-regulated. Conclusion GMP-Na;has the protective effect on mice with liver injury induced by LPS/D-GalN. It can inhibit the induced liver inflammation and oxidative stress response, and its mechanism may be related to inhibition of caspase 3/bax/bcl-2 apoptosis signal pathway.

关 键 词：鸟苷酸二钠 肝损伤 Caspase 3/Bax/Bcl-2 

分 类 号：R114[医药卫生—卫生毒理学]