摘要
[背景]慢性低浓度铅(后简称"低铅")中毒已成为影响人们健康的一大疾病,尤其是当肝脏自身受到炎症、脂肪等浸润时,其排铅能力明显降低,会加重肝脏的损害,其作用机制可能与细胞凋亡有关。[目的]本研究拟从肝细胞凋亡途径探讨低铅对非酒精性脂肪肝病大鼠的影响,以进一步明确低铅在肝脏损害中的作用。[方法]适应性喂养2周后,60只SD大鼠随机均分为4组,为普通饲料组(后称"普通组")、低铅普通饲料组(后称"低铅组")、高脂饲料组(后称"高脂组")和低铅高脂饲料组(后称"低铅高脂组"),每组15只。相应饲料喂养8周后处死。采集肝脏和血液,检测血铅和肝铅含量,观察光镜下肝脏形态学变化,观察其肝功能指标[血清谷草转氨酶(AST)和谷丙转氨酶(ALT)]、抗氧化指标[血清超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽(GSH)和总抗氧化能力(T-AOC)],并采用Westernblot和逆转录-聚合酶链反应(RT-PCR)检测凋亡相关Bax、bcl-2、P53和Fas蛋白和mRNA的表达。[结果]低铅组和低铅高脂组大鼠血铅和肝铅含量明显高于普通组(P<0.05),且低铅高脂组血铅[(0.31±0.10)mg/L]和肝铅[(3.37±1.12)mg/L]明显高于低铅组[(0.26±0.10)mg/L,(2.42±0.87)mg/L](P<0.05)。HE染色显示:普通组大鼠肝脏细胞排列紧密,细胞核大小均一;低铅组看不出明显损伤;高脂组和低铅高脂组有明显脂肪空泡,特别是低铅高脂组,脂肪空泡数量更多,表明大鼠非酒精性脂肪肝病模型建成。低铅组、高脂组和低铅高脂组ALT和AST均明显高于普通组(P<0.05);高脂组和低铅高脂组ALT和AST明显高于低铅组(P<0.05);低铅高脂组ALT和AST明显高于高脂组(P<0.05)。低铅组SOD、GSH、T-AOC和MDA与普通组没有差异;相较于普通组,高脂组和低铅高脂组SOD、GSH和T-AOC明显降低(P<0.05),MDA明显升高(P<0.05);相较于低铅普通组,高脂组和低铅高脂组SOD、GSH和T-AOC明显降低(P<0.05),MDA明显升高(P
[Background] Chronic low lead poisoning affects human health;especially when liver is experiencing inflammatory and fatty infiltration, it removes less lead and the damage aggravates, which may be related to cell apoptosis.[Objective] This study is designed to investigate the effects of low lead on hepatocyte apoptosis in rats with non-alcoholic fatty liver disease(NAFLD), and clarify the role of low lead in liver damage.[Methods] After two weeks of adaptive feeding, 60 rats were randomly divided into four groups: normal diet group, low Pb group, high fat diet group, and low Pb+high fat diet group, with 15 rats in each group. They were sacrificed after feeding with corresponding diet plans for eight weeks. Liver and blood samples were collected to detect blood and liver lead levels, liver function indices [aspartate transaminase(AST) and alanine transaminase(ALT)], and antioxidant indices [superoxide dismutase(SOD), malondialdehyde(MDA), glutathione(GSH), and total antioxidant capacity(T-AOC)], as well as to observe liver pathological alteration under light microscope. The protein and mRNA expressions of Bax, bcl-2, P53, and Fas were measured by Western blot and reverse transcription-polymerase chain reaction(RT-PCR), respectively.[Results] The levels of blood lead and liver lead in the low Pb group and the low Pb+high fat diet group were significantly higher than those in the normal diet group(P < 0.05), and the levels in the low Pb+high fat diet group [blood lead:(0.31±0.10) mg/L;liver lead:(3.37±1.12) mg/L] were significantly higher than those in the low Pb group [blood lead:(0.26±0.10) mg/L;liver lead:(2.42±0.87) mg/L](P < 0.05). The results of HE staining showed that cells on rat liver in the normal diet group were closely arranged with uniform nucleus size;the low Pb group did not show obvious damage;the high fat diet group and the low Pb+high fat diet group showed fat vacuoles, especially the low Pb+high fat diet group, indicating an established rat model of NAFLD. For AST and ALT, the low Pb group, th
作者
朱为梅
赵红宇
杨海清
罗宇超
李学章
ZHU Wei-mei;ZHAO Hong-yu;YANG Hai-qing;LUOYu-chao;LI Xue-zhang(Department of Occupational Diseases,The Third People's Hospital of YunnanProvince/Yunnan Occupational Disease Hospital,Kunming,Yunnan 650011,China)
出处
《环境与职业医学》
CAS
CSCD
北大核心
2019年第5期490-495,共6页
Journal of Environmental and Occupational Medicine
基金
云南卫生科技计划项目(2016NS336)
关键词
低铅
高脂
非酒精性脂肪肝
肝细胞凋亡
low lead
high fat diet
non-alcoholic fatty liver
hepatocyte apoptosis
