Page 7 - 南京医科大学学报自然科学版

第42卷第2期 南京医科大学学报（自然科学版）
2022年2月 Journal of Nanjing Medical University（Natural Sciences） ·153 ·

·基础医学·

神经节苷脂 GM3在非酒精性脂肪肝炎小鼠肝脏中的表达变化

胡默然，吴周璐，赵晨曦，龚颖芸，周红文 *
南京医科大学第一附属医院内分泌科，江苏 南京 210029

［摘 要］ 目的：探究高脂高糖饮食诱导的非酒精性脂肪肝炎（non⁃alcoholic steatohepatitis，NASH）小鼠模型较对照组肝脏内
单唾液酸神经节苷脂 3（monosialodihexosylganglioside，GM3）等鞘糖脂的变化。方法：16只6周龄C57BL/6J小鼠随机分为对照
组和模型组，每组8只，对照组喂普通饲料，正常饮水；模型组喂高脂饲料，含糖饮水（23.1 g/L蔗糖+18.9 g/L葡萄糖）。检测两
组小鼠血清生化指标丙氨酸氨基转移酶（alanine aminotransferase，ALT）、天门冬氨酸氨基转移酶（aspartate aminotransferase，
AST），采用HE染色观察两组小鼠肝脏组织病理变化。使用Exion UPLC⁃QTRAP 6500 PLUS（Sciex）液质联用仪，以电喷雾电离
（ESI）模式进行脂质组学分析。采用独立样本t检验、曼⁃惠特尼检验进行组间差异的统计学分析。结果：①高脂高糖饮食喂养
7个月组小鼠较普通饲料喂养组ALT、AST水平显著升高（P < 0.05）。②模型组较对照组显著降低的指标有肝脏内总GM3（P=
0.016）及GM3 d18：1/20：0（P=0.005）、GM3 d18：1/22：0（P=0.004）、GM3 d18：1/24：0（P=0.004）和GM3 d18：1/26：0（P=0.042），总
神经酰胺、总乳糖神经酰胺等显著升高（P < 0.05）。结论：高脂高糖饮食喂养的NASH模型小鼠肝脏中经乳糖神经酰胺向GM3
转化的合成通路受阻。
［关键词］ NASH；神经节苷脂GM3；鞘糖脂；ST3GAL5
［中图分类号］ R575.5 ［文献标志码］ A ［文章编号］ 1007⁃4368（2022）02⁃153⁃07
doi：10.7655/NYDXBNS20220201

Expression of ganglioside GM3 in the liver of mice with nonalcoholic steatohepatitis

HU Moran，WU Zhoulu，ZHAO Chenxi，GONG Yingyun，ZHOU Hongwen *
Department of Endocrinology and Metabolism，the First Affiliated Hospital of Nanjing Medical University，Nanjing
210029，China

［Abstract］ Objective：This study aims to investigate the changes of glycosphingolipid，especially the ganglioside GM3，in the liver
of NASH model mice induced by high ⁃ fat and high ⁃ sugar diet . Methods：A total of 16 C57BL/6J mice aged 6 ⁃ weeks old were
randomly allocated into control group and NASH group（control n=8；NASH n=8）. Control mice were fed with a standard chow diet and
water as control group，while the other mice were fed high fat diet accompanied by ad libitum consumption of water with high fructose
and glucose content（23.1 g/L d⁃fructose +18.9 g/L d⁃glucose）to establish NASH models as model group. Serum levels of ALT and AST
were measured to evaluate the pathological changes of liver tissues. Liver histology was assessed using HE stains in paraffin⁃embedded
sections using standard commercially used methods. Liver lipidomics analysis was perfonned in an electrospray ionization mode using
Exion UPLC⁃QTRAP 6500 PLUS（Sciex）LC/MS. The student’s t test and Mann⁃Whitney U test were used for statistical analysis.
Results：① The levels of alanine aminotransferase（ALT）and aspartate aminotransferase（AST）in NASH mice were significantly
higher than that in control group（P < 0.05）. ②Compared with the control group，total GM3 and subtype species，including GM3 d18：1/
20：0（P=0.005），GM3 d18：1/22：0（P=0.004），GM3 d18：1/24：0（P=0.004）and GM3 d18：1/26：0（P=0.042）were significantly lower
in the model group，which were dignosed as NASH group based on the NAFLD activity score. Conversely，total ceramide and total
lactosylceramide（LacCer）were remarkably elevated in NASH group than control group（P < 0.05）. Conclusion：The synthetic
pathway from LacCer to GM3 is dampened in NASH model mice，which are established by high⁃fat and high⁃fructose diet.
［Key words］ NASH；ganglioside GM3；glycosphingolipid；ST3GAL5
［J Nanjing Med Univ，2022，42（02）：153⁃159］

［基金项目］ 国家自然科学基金（81730094，31900832）；江苏省科技厅自然科学青年基金（BK20191074）
∗
通信作者（Corresponding author），E⁃mail：drhongwenzhou@njmu.edu.cn