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浙江大学学报（医学版）
浙江大学学报（医学版）  2021, Vol. 50 Issue (6): 755-761    DOI: 10.3724/zdxbyxb-2021-0178
原著     
宫内发育迟缓出生后追赶生长大鼠脂肪组织LRP6/β-catenin通路表达变化
曹秋丽,黎小炜,禤秀萍,黄松,谢雪梅()
广西医科大学第一附属医院内分泌科，广西 南宁 530021
Changes of LRP6/β-catenin pathway in adipose tissue of rats with intrauterine growth restriction with catch-up growth
CAO Qiuli,LI Xiaowei,XUAN Xiuping,HUANG Song,XIE Xuemei()
Department of Endocrinology, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China
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摘要：

目的：探讨宫内发育迟缓出生后追赶生长（CG-IUGR）大鼠脂肪组织低密度脂蛋白受体相关蛋白6（LRP6）/β-联蛋白（β-catenin）通路表达变化。方法：随机将SD孕鼠分为两组，一组孕鼠全程限食喂养，生产后通过减少喂养子鼠数量，建立子鼠CG-IUGR模型（CG-IUGR组）；另一组孕鼠正常喂养，生产的子鼠作为对照组。为排除性别因素的干扰，CG-IUGR组和对照组均选取雄性子鼠。CG-IUGR组和对照组在12周龄时进行葡萄糖耐量试验，并取肾周脂肪组织标本，通过苏木素-伊红染色观察脂肪结构，共聚焦显微镜下观察脂肪组织LRP6、β-catenin及胰岛素受体底物1（IRS-1）的免疫活性，蛋白质印迹法检测LRP6、β-catenin、IRS-1蛋白表达。结果：CG-IUGR组在60?min时血糖浓度及曲线下面积均大于对照组（均P<0.05），表明CG-IUGR组葡萄糖耐量受损。CG-IUGR组脂肪细胞面积较对照组增大，脂肪组织中LRP6、β-catenin和IRS-1免疫活性较对照组降低（均P<0.05）。结论：CG-IUGR大鼠脂肪组织胰岛素抵抗可能与LRP6/β-catenin通路表达下调有关。
关键词： 宫内发育迟缓;  追赶生长;  脂肪组织;  胰岛素抵抗;  LRP6/β-catenin通路;  大鼠    
Abstract:

Objective: To investigate the expression of low-density lipoprotein receptor-related protein 6 (LRP6)/β-catenin pathway related proteins in adipose tissue of rats with intrauterine growth restriction with catch-up growth (CG-IUGR). Methods: SD rats were randomly divided into nutrition-restriction rats and normal feed rats during pregnancy. CG-IUGR model was established by reducing the number of offspring in the nutrition-restriction rats (CG-IUGR group); while the rats in the control group were offspring of the normal feed pregnant rats. In order to exclude the interference of gender, male offspring mice were selected in both the CG-IUGR group and the control group in the following studies. The CG-IUGR group and the control group were subjected to glucose tolerance test at 12 weeks of age, and the perirenal adipose tissue samples were taken to observe the adipose structure by HE staining. Expression of LRP6, β-catenin and insulin receptor substrate 1 (IRS-1) in adipocytes were examined by confocal microscopy. Protein expression of LRP6, β-catenin and IRS-1 were measured by Western blotting. Results: Blood glucose level and the area under the cure of CG-IUGR group were significantly higher than that of control group (both P<0.05). Adipocyte size in the CG-IUGR group was significantly larger than that of control group, and the expression of LRP6, β-catenin and IRS-1 protein in adipose tissue of the CG-IUGR group was significantly lower than that of control group (allP<0.05).Conclusion: The expression of LRP6/β-catenin pathway related proteins is reduced in the adipose tissue in CG-IUGR rats, probably contributing to the insulin resistance in these rats.
Key words: Intrauterine growth restriction    Catch-up growth    Adipose tissue    Insulin resistance    LRP6/β-catenin pathway    Rats
收稿日期: 2021-06-27 出版日期: 2022-03-22
CLC:  R589.2  
基金资助: 国家自然科学基金（81660268）
通讯作者: 谢雪梅     E-mail: xiexuemei1234@163.com
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引用本文:

曹秋丽,黎小炜,禤秀萍,黄松,谢雪梅. 宫内发育迟缓出生后追赶生长大鼠脂肪组织LRP6/β-catenin通路表达变化[J]. 浙江大学学报（医学版）, 2021, 50(6): 755-761.

CAO Qiuli,LI Xiaowei,XUAN Xiuping,HUANG Song,XIE Xuemei. Changes of LRP6/β-catenin pathway in adipose tissue of rats with intrauterine growth restriction with catch-up growth. J Zhejiang Univ (Med Sci), 2021, 50(6): 755-761.

链接本文:

https://www.zjujournals.com/med/CN/10.3724/zdxbyxb-2021-0178    或    https://www.zjujournals.com/med/CN/Y2021/V50/I6/755

图1  两组出生后体重变化与对照组比较，<0.05. CG-IUGR：宫内发育迟缓出生后追赶生长.
图2  两组12周龄时糖耐量试验结果与对照组比较，<0.05. CG-IUGR：宫内发育迟缓出生后追赶生长.
图3  两组12周龄时肾周脂肪组织HE染色结果CG-IUGR组雄性大鼠肾周脂肪组织较对照组显著增大.CG-IUGR：宫内发育迟缓出生后追赶生长. 标尺=100 μm.
图4  两组12周龄时肾周脂肪组织LRP6、β-catenin、IRS-1免疫荧光检测结果LRP6主要在细胞膜上表达，β-catenin主要在细胞质及细胞核表达，IRS-1在细胞质表达，均呈红色. 对照组LRP6、β-catenin、IRS-1表达高于CG-IUGR组. CG-IUGR：宫内发育迟缓出生后追赶生长；IRS-1：胰岛素受体底物1；LRP6：低密度脂蛋白受体相关蛋白6. 标尺=75 μm.
图5  两组12周龄时肾周脂肪组织LRP6、β-catenin、IRS-1蛋白表达电泳图A1、A2、A3为对照组；I1、I2、I3为CG-IUGR组. CG-IUGR：宫内发育迟缓出生后追赶生长；IRS-1：胰岛素受体底物1；LRP6：低密度脂蛋白受体相关蛋白6.
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