首 页   本刊简介  编委会  审稿专家  在线期刊  写作规范  广告合作  联系我们
您现在的位置:首页 => 在线期刊 => 2019年 10期HBV感染“新型”生物标志物的临床应用 => 其他 =>JNK1基因沉默对非..
JNK1基因沉默对非酒精性脂肪性肝病小鼠模型高分子量脂联素表达的影响
Effect on JNK1 gene silencing on the expression of high-molecular-weight adiponectin in mice with nonalcoholic fatty liver disease
文章发布日期:2019年09月05日  来源:  作者:赵晓芳,唐友明,徐新杰,等  点击次数:121次  下载次数:15次

调整字体大小:

(此处下载失败可以在在线预览处保存副本或者右键另存为)

【摘要】: 目的 探讨JNK1基因沉默对非酒精性脂肪性肝病(NAFLD)小鼠脂肪组织高分子量脂联素(HMW-APN)及相关通路分子的影响。方法 20只C57BL/6小鼠被随机分为正常组、模型对照组、shRNA-JNK1慢病毒处理NAFLD组(JNK1+NAF组)、无关序列shRNA慢病毒处理NAFLD组(无关序列+NAF组),每组5只。正常饮食与高脂饮食分别喂养3个月,成功复制NAFLD小鼠模型,利用最佳干扰效果的shRNA-JNK1慢病毒和无关序列shRNA慢病毒通过尾静脉注射NAFLD小鼠。根据各组饮食及慢病毒注射情况喂养5 d后,HE染色观察各组小鼠肝组织的病理学改变。ELISA方法检测各组小鼠血清中HMW-APN的水平。取附睾脂肪垫行Western Blot检测分析AMPK、P-AMPK、HMW-APN、DsbA-L的表达水平。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检验。结果 经HE染色,JNK1+NAF组较模型对照组脂滴空泡减少,水肿、炎症减轻。JNK1+NAF组的肝组织脂肪变评分(2.267±0.704)较模型对照组(3.800±0.414)和无关序列+NAF组(3.667±0.617)评分明显降低(P值均<0.05)。经ELISA分析,JNK1+NAF组的血清HMW-APN水平[(294.71±102.30)ng/ml]较模型对照组[(124.06±70.58)ng/ml]明显升高(P<0.001)。经Western Blot分析,与模型对照组和无关序列+NAF组比较,JNK1+NAF组AMPK、P-AMPK、DsbA-L和HMW-APN表达水平明显升高(P值均<0.05)。结论 JNK1基因沉默促进NAFLD小鼠DsbA-L和HMW-APN表达,且JNK1基因沉默可能活化AMPK通路实现对脂联素多聚化调控,从而改善NAFLD脂肪沉积。
【Abstract】: Objective To investigate the effect of JNK1 gene silencing on the expression of high-molecular-weight adiponectin and related pathway molecules in adipose tissue of mice with nonalcoholic fatty liver disease (NAFLD). Methods A total of 20 C57BL/6 mice were randomly divided into normal group, model control group, NAFLD group treated with shRNA-JNK1 lentivirus (JNK1+NAF group), and NAFLD group treated with unrelated-sequence shRNA lentivirus (unrelated sequence+NAF group), with 5 mice in each group. Normal diet and high-fat diet were given for 3 months, and a mouse model of NAFLD was successfully established. The mice with NAFLD were given tail vein injection of shRNA-JNK1 lentivirus with the optimal interfering effect and unrelated-sequence shRNA lentivirus. After 5 days of feeding based on diet and lentivirus injection, HE staining was used to observe the pathological changes of liver tissue. ELISA was used to measure the serum level of high-molecular-weight adiponectin. Western blot was used to measure the expression of AMP-activated protein kinase (AMPK), phosphorylated AMPK (p-AMPK), high-molecular-weight adiponectin, and disulfide-bond-A oxidoreductase-like protein (DsbA-L) in epididymal fat pad. A one-way analysis of variance was used for comparison of continuous data between groups, and the least significant difference t-test was used for further comparison between two groups. Results HE staining showed that compared with the model control group, the JNK1+NAF group had significant reductions in lipid droplet vacuoles, edema, and inflammation. The JNK1+NAF group had a significantly lower liver steatosis score than the model control group and the unrelated sequence+NAF group (2.267±0.704 vs 3.800±0.414/3.667±0.617, both P<0.05). ELISA showed that the JNK1+NAF group had a significantly higher serum level of high-molecular-weight adiponectin than the model control group (294.71±102.30 ng/ml vs 124.06±70.58 ng/ml, P<0.001). Western Blot showed that the JNK1+NAF group had significantly higher expression levels of AMPK, p-AMPK, DsbA-L, and high-molecular-weight adiponectin than the model control group and the unrelated sequence+NAF group (all P<0.05). Conclusion JNK1 gene silencing can promote the expression of DsbA-L and high-molecular-weight adiponectin in NAFLD mice, activate the AMPK pathway to regulate adiponectin multimerization, and thus improve fat deposition in NAFLD.
【关键字】:非酒精性脂肪性肝病; 基因沉默; 脂联素; 小鼠, 近交C57BL
【Key words】:nonalcoholic fatty liver disease; gene silencing; adiponectin; mice, inbred C57BL
【引证本文】:ZHAO XF, TANG YM, XU XJ, et al. Effect on JNK1 gene silencing on the expression of high-molecular-weight adiponectin in mice with nonalcoholic fatty liver disease[J]. J Clin Hepatol, 2019, 35(10): 2257-2260. (in Chinese)
赵晓芳, 唐友明, 徐新杰, 等. JNK1基因沉默对非酒精性脂肪性肝病小鼠模型高分子量脂联素表达的影响[J]. 临床肝胆病杂志, 2019, 35(10): 2257-2260.

地址:长春市东民主大街519号《临床肝胆病杂志》编辑部 邮编:130061 电话:0431-88782542/3542
临床肝胆病杂志 版权所有 Copyright © 2009 - 2013 Lcgdbzz.org. All Rights Reserv 吉ICP备10000617号

吉公网安备 22010402000041号