刺梨汁对砷诱导的大鼠肝脏S-腺苷甲硫氨酸消耗及肝损伤的改善作用  

Rosa roxburghii Tratt juice can improve S-adenosylmethionine consumption and liver damage induced by arsenic in rats

作　　者：马璐[1] 吕佳鑫 杨璐铭 罗道朋 朱凯[1] 张爱华[1] MA Lu;LYU Jiaxin;YANG Luming;LUO Daopeng;ZHU Kai;ZHANG Aihua(Key Laboratory of Environmental Pollution Monitoring and Disease Control,Ministry of Education/Department of Toxicology,School of Public Health,Guizhou Medical University,Guiyang,Guizhou 550025,China)

机构地区：[1]贵州医科大学,环境污染与疾病监控教育部重点实验室/公共卫生与健康学院卫生毒理学系,贵州贵阳550025

出　　处：《环境与职业医学》2023年第12期1387-1394,共8页Journal of Environmental and Occupational Medicine

基　　金：国家自然科学基金重点项目(81430077)。

摘　　要：[背景]砷可引起肝脏功能紊乱、脂肪变性、炎症、纤维化等不同程度肝损伤,但其机制尚不明确且缺乏有效治疗手段。[目的]从S-腺苷甲硫氨酸(SAM)代谢角度初步探讨刺梨汁对砷致大鼠肝损伤的干预作用及机制。[方法]36只Wistar大鼠按随机数字法分为6组,每组6只,雌雄各半。低、中、高砷剂量组分别给予2.5、5.0、10.0 mg·kg^(−1)亚砷酸钠(NaAsO_(2))(以体重计,后同)灌胃,对照组给予10 mL·kg^(−1)去离子水灌胃;刺梨汁干预组给予10 mg·kg^(−1)NaAsO_(2)灌胃4 h后给予10 mL·kg^(−1)刺梨汁灌胃;刺梨汁对照组给予10 mL·kg^(−1)刺梨汁灌胃;每天灌胃1次,每周灌胃6 d,共处理4个月。苏木素-伊红染色(HE染色)观察大鼠肝脏组织病理学改变;酶循环法、速率法分别检测大鼠肝功能指标总胆汁酸(TBA)、谷氨酰胺转移酶(γ-GT);超高效液相色谱(UPLC-MS)检测大鼠肝脏SAM、S-腺苷同型半胱氨酸(SAH)含量;实时荧光定量逆转录PCR(RT-qPCR)检测大鼠肝脏中SAM代谢相关酶甘氨酸-N-甲基转移酶(GNMT)、烟酰胺N-甲基转移酶(NNMT)、磷脂酰乙醇胺N-甲基转移酶(PEMT)基因(Gnmt、Nnmt、Pemt)的mRNA水平。[结果]对照组大鼠肝细胞核染清晰,胞浆染色均匀,肝索呈放射状排列,无炎性细胞浸润;低、中、高砷剂量组可见不同程度的肝窦扩张、充血,炎性浸润。与对照组比较,中、高砷组TBA及高砷组γ-GT明显增加(P<0.05),且随染砷剂量增加逐渐升高(P趋势<0.05)。与对照组相比,低、中、高砷剂量组SAH含量明显增高,SAM含量、SAM/SAH明显降低(P<0.05),且均与染砷剂量呈剂量-反应关系(P趋势<0.05);SAM、SAM/SAH的降低与大鼠肝功能指标TBA(SAM:r=−0.569;SAM/SAH:r=−0.607)、γ-GT(SAM:r=−0.577;SAM/SAH:r=−0.622)的增加相关(P<0.05)。此外,与对照组相比,高砷剂量组Gnmt及低、中、高砷剂量组Nnmt、Pemt基因mRNA表达水平均明显上升(P<0.05),且随染砷剂量升高呈上升趋势(P[Background]Arsenic exposure can lead to liver dysfunction,liver steatosis,hepatitis,liver fibrosis,and other liver injuries,but its mechanism is still unclear and effective treatment methods are lacking.[Objective]To investigate the potential intervention effect and associated mechanism of Rosa roxburghii Tratt juice on arsenic-induced liver injury in rats from the perspective of S-adenosylmethionine(SAM)metabolism.[Methods]Thirty-six Wistar rats were randomly divided into six groups,six rats in each group,half male and half female.The low,medium,and high dose groups of sodium arsenite(NaAsO_(2))were given 2.5,5.0,and 10.0 NaAsO_(2)mg·kg^(−1)(body weight,thereafter),respectively;the control group was given 10 mL·kg^(−1)deionized water;the Rosa roxburghii Tratt juice intervention group was given 10 mg·kg^(−1)NaAsO_(2)for 4 h and then 10 mL·kg^(−1)Rosa roxburghii Tratt juice;the Rosa roxburghii Tratt juice control group was given 10 mL·kg^(−1)Rosa roxburghii Tratt juice by gavage.All rats were gavaged once a day,6 d per week for 4 months.Histopathological changes of rat liver were observed by hematoxylin-eosin(HE)staining.Total bile acids(TBA)andγ-glutamyl transpeptidase(γ-GT)were detected by enzyme cycle method and rate method,respectively.Ultra-high-performance liquid chromatography tandem mass spectrometry(UPLC-MS)was used to evaluate SAM and S-adenosylhomo cysteine(SAH)in rat liver.Real-time fluorescence quantitative reverse transcriptional PCR(RTqPCR)was used to detect the mRNA expression levels of the genes of glycine-N-methyltransferase(Gnmt),nicotinamide-N-methyltransferase(Nnmt),and phosphatidylethano-lamine N-mathyltransferase(Pemt).[Results]In the control group,the liver nuclei were stained clearly,the cytoplasm was stained uniformly,and the liver cords were arranged radially without inflammatory infiltration.In the low,medium,and high dose groups of NaAsO_(2),hepatic sinusoidal dilation,congestion,and inflammatory infiltration were observed to different degrees.Compared with the contro

关 键 词：亚砷酸钠 刺梨汁 肝损伤 S-腺苷甲硫氨酸 甲基转移酶 

分 类 号：R114[医药卫生—卫生毒理学]