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黄连素对2型糖尿病仓鼠骨形态发生蛋白4转录途径基因表达的调控作用以改善内脏白色脂肪组织胰岛素抵抗

[Regulations of berberine on gene expression of BMP4 transcriptional pathways to improve visceral white adipose tissues insulin resistance in type 2 diabetic hamsters].

作者信息

Li Guo-Sheng, Liu Xu-Han, Li Xin-Yu, Gao Zheng-Nan, Huang Lan, Liu Ya-Li

机构信息

Department of Pathology, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, China.

Department of Endocrinology, Dalian Municipal Central Hospital Affiliated to Dalian Medical University, Dalian 116033, China.

出版信息

Zhongguo Zhong Yao Za Zhi. 2016 Feb;41(3):514-520. doi: 10.4268/cjcmm20160326.

Abstract

To study the effects of berberine on the gene mRNA expressions of BMP4 transcriptional pathways and brown/white adipose tissue conversion transcriptional pathways in visceral white adipose tissues(VWAT) in type 2 diabetic hamsters and explore the relevant mechanisms. The obese insulin-resistant hamster model were induced by using high-fat diet, and then the type 2 diabetic hamster model was created through injection with low-dose streptozotocin in the obese insulin-resistant hamster model. After the modeling, the hamsters were randomly divided into normal control, obese insulin-resistant, type 2 diabetic and berberine-treated diabetic groups. After the nine-week treatment, real-time quantitative PCR was used to measure the changes in gene mRNA expressions of VWAT BMP4 transcriptional pathways, brown/white adipose tissue conversion transcriptional pathways and their target genes in different groups. The results showed that the gene mRNA expressions of BMP4, BMPRⅡ, BMPRlA, Smad1, Smad5, Smad8, p38/MAPK, ATF2, PRDM16, C/EBPβ, PGC1α, PPARγ and brown adipose tissue-specific genes was decreased and that of Smad6, Smurf1 and white adipose tissue-specific genes was increased in VWAT of model hamsters. Treatment with berberine regulated BMP4 transcriptional pathways and brown adipose tissue transcriptional pathways and induced the gene mRNA expression of brown adipose tissue-specific genes in VWAT to develop browning gene phenotype of white adipose tissues, and then improved fat-induced insulin resistance. These findings indicated that BMP4 transcriptional pathways involved in the formation of fat-induced visceral white adipose tissues insulin resistance (FIVWATIR) and the browning molecular mechanism of white adipose tissues induced by berberine.

摘要

研究小檗碱对2型糖尿病仓鼠内脏白色脂肪组织(VWAT)中BMP4转录通路及棕色/白色脂肪组织转化转录通路基因mRNA表达的影响,并探讨其相关机制。采用高脂饮食诱导肥胖胰岛素抵抗仓鼠模型,然后在肥胖胰岛素抵抗仓鼠模型中注射低剂量链脲佐菌素建立2型糖尿病仓鼠模型。造模后,将仓鼠随机分为正常对照组、肥胖胰岛素抵抗组、2型糖尿病组和小檗碱治疗糖尿病组。经过9周治疗后,采用实时定量PCR检测不同组VWAT中BMP4转录通路、棕色/白色脂肪组织转化转录通路及其靶基因的基因mRNA表达变化。结果显示,模型仓鼠VWAT中BMP4、BMPRⅡ、BMPRlA、Smad1、Smad5、Smad8、p38/MAPK、ATF2、PRDM16、C/EBPβ、PGC1α、PPARγ及棕色脂肪组织特异性基因的基因mRNA表达降低,Smad6、Smurf1及白色脂肪组织特异性基因的基因mRNA表达升高。小檗碱治疗可调节BMP4转录通路和棕色脂肪组织转录通路,诱导VWAT中棕色脂肪组织特异性基因的基因mRNA表达,使白色脂肪组织呈现棕色化基因表型,进而改善脂肪诱导的胰岛素抵抗。这些研究结果表明,BMP4转录通路参与脂肪诱导的内脏白色脂肪组织胰岛素抵抗(FIVWATIR)的形成以及小檗碱诱导白色脂肪组织棕色化的分子机制。

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