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低铅对非酒精性脂肪性肝病大鼠模型肝功能和血脂的影响
Influence of low-level lead exposure on liver function and blood lipids in rats with nonalcoholic fatty liver disease
文章发布日期:2019年03月07日  来源:  作者:朱为梅,王秀芳,杨海清,等  点击次数:314次  下载次数:69次

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【摘要】:目的探讨低铅高脂饲料摄入对非酒精性脂肪性肝病大鼠模型肝功能和血脂的影响,并从脂肪酸合成途径研究肝脏脂肪酸合成相关酶固醇调节原件结合蛋白(SREBP-1c)、脂肪酸合酶(FAS)和乙酰CoA羧化酶(ACCα)表达特点。方法清洁级雄性SD大鼠40只,适应性喂养14 d后随机分为正常组(A组)、低铅染毒组(B组)、高脂饲料组(C组)和低铅染毒高脂饲料组(D组),每组各10只,相应饲料喂养8周后处死大鼠,收集血清和肝脏检测血铅、肝功能、血脂、肝脏病理学,采用Western Blot和RT-PCR检测脂肪酸合成相关蛋白酶SREBP-1c、FAS和ACCα蛋白及mRNA的表达特点。计量资料多组间比较采用单因素方差分析,进一步两两比较采用LSD-t法。结果肝脏组织病理学可见,A组和B组切片表面光滑,细胞核分布均匀且大小均一,没有明显脂肪细胞浸润和炎症反应,而C组和D组则出现明显的脂肪浸润,且有一定的炎症浸润,特别是D组,脂肪空泡更大。大鼠血铅和肝铅含量,多组间比较差异均有统计学意义(F值分别为37.792、21.458,P值均<0.001);相较于A组,B组和D组血铅和肝铅明显升高(P值均<0.05);相较于B组和C组,D组血铅和肝铅均明显升高(P值均<0.05)。大鼠肝功能指标AST、ALT、HDL-C、LDL-C,4组间比较差异均有统计学意义(F值分别为35.791、24.422、37.287、42.371,P值均<0.001);相较于A组,B、C和D 3组大鼠AST、ALT、HDL-C、LDL-C均升高(P值均<0.05),相较于B组,C组和D组4个指标明显升高(P值均<0.05);相较于C组,D组4个指标明显升高(P值均<0.05)。SREBP-1c、FAS和ACCα蛋白及mRNA表达特点基本一致,4组间比较差异均有统计学意义(蛋白:F值分别为21.864、22.358、57.761,P值均<0.001;mRNA:F值分别为34.652、22.964、42.384,P值均<0001);相较于A组和B组,C组以及D组肝脏组织中SREBP-1c、FAS和ACCα蛋白及mRNA表达均明显升高(P值均<0.05),D组均明显高于C组(P值均<0.05))。结论低铅染毒可加重非酒精性脂肪性肝病大鼠模型肝功能和血脂异常,其原因可能与高脂和铅的长期摄入增加SREBP-1c、FAS和ACCα表达有关。
【Abstract】:ObjectiveTo investigate the influence of low-lead high-fat diet on liver function and blood lipids in rats with nonalcoholic fatty liver disease (NAFLD), as well as the expression of sterol regulatory element-binding protein-1c (SREBP-1c), fatty acid synthase (FAS), and acetyl-CoA carboxylase α (ACCα) in the liver from the aspect of the fatty acid synthesis pathway. MethodsA total of 40 clean male Sprague-Dawley rats were given adaptive feeding for 14 days and were then randomly divided into normal group, low-lead exposure group, high-fat diet group, and low-lead high-fat diet group, with 10 rats in each group. The rats were sacrificed after 8 weeks of feeding with the corresponding diet, and serum and liver samples were collected to measure blood lead, liver function, blood lipids, and liver pathology. Western blot and RT-PCR were used to measure the protein and mRNA expression of SREBP-1c, FAS, and ACCα involved in fatty acid synthesis. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. ResultsThere were marked liver pathological changes after exposure. The sections from the normal group and the low-lead exposure group had a smooth surface and evenly distributed nuclei, without marked adipocyte infiltration or inflammatory response; the sections from the low-lead high-fat diet group and the high-fat diet group had marked fatty infiltration and inflammatory cell infiltration, and those from the low-lead high-fat diet group had larger fat vacuoles. There were significant differences in blood lead and liver lead between groups (F=37.792 and 21.458, both P<0.001), and the low-lead exposure group and the low-lead high-fat diet group had significantly higher levels than the normal group (all P<0.05). There were significant differences in aspartate aminotransferase (AST), alanine aminotransferase (ALT), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) between groups (F=35.791, 24.422, 37.287, and 42.371, all P<0001), and the low-lead exposure group, the high-fat diet group, and the low-lead high-fat diet group had significantly higher AST, ALT, LDL-C, and HDL-C than the normal group (all P<0.05). Western blot and RT-PCR showed consistent protein and mRNA expression features of SREBP-1c, FAS, and ACCα, and there were significant differences in the protein and mRNA expression of REBP-1c, FAS, and ACCα between groups (protein expression: F=21.864, 22.358, and 57.761, all P<0.001; mRNA expression: F=34652, 22.964, and 42.384, all P<0.001). Compared with the normal group and the low-lead exposure group, the high-fat diet group and the low-lead high-fat diet group had significant increases in the protein and mRNA expression of SREBP-1c, FAS, and ACCα in the liver (all P<0.05). ConclusionLow-lead exposure can aggravate liver function and dyslipidemia in NAFLD rats, possibly by regulating the expression of SREBP-1c, FAS, and ACCα.
【关键字】:非酒精性脂肪性肝病; 铅中毒; 脂肪酸合成酶复合物; 乙酰CoA羧化酶; 大鼠, Sprague-Dawley
【Key words】:fatty liver; lead poisoning; fatty acid synthetase complex;acetyl-CoA carboxylase; rats, Sprague-Dawley
【引证本文】:ZHU WM, WANG XF, YANG HQ, et al. Influence of low-level lead exposure on liver function and blood lipids in rats with nonalcoholic fatty liver disease[J]. J Clin Hepatol, 2019, 35(4): 840-845. (in Chinese)
朱为梅, 王秀芳, 杨海清, 等. 低铅对非酒精性脂肪性肝病大鼠模型肝功能和血脂的影响[J]. 临床肝胆病杂志, 2019, 35(4): 840-845.

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