[Molecular mechanism of Gegen Qinlian Decoction in promoting differentiation of brown adipose tissue to improve glucose and lipid metabolism disorders in diabetic rats].
[Molecular mechanism of Gegen Qinlian Decoction in promoting differentiation of brown adipose tissue to improve glucose and lipid metabolism disorders in diabetic rats].
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DOI：
10.19540/j.cnki.cjcmm.20210524.403
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发表时间：
2021-09
期刊：
影响因子：
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通讯作者：
Xiao-Qing Zhang;Wencai Xu;Xin-xia Xiao;Jun-Feng Ding;Yue-Fei Jiang;Jun-Da Tu
中科院分区：
文献类型：
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作者：
Xiao-Qing Zhang;Wencai Xu;Xin-xia Xiao;Jun-Feng Ding;Yue-Fei Jiang;Jun-Da Tu
本研究旨在探讨葛根芩连汤促进棕色脂肪组织分化改善糖尿病大鼠糖脂代谢紊乱的分子机制。在证实GQD对高脂饮食联合小剂量链脲佐菌素诱导的糖尿病大鼠具有降血糖作用后，提取大鼠肩胛骨周围BAT的总RNA。采用qPCR方法检测核转录基因Prdm 16、Pparγc1α、Pparα、Pparγ和Sirt 1，BAT标记基因Ucp 1、Cidea和Dio 2，能量消耗基因Ampkα2以及BAT分泌因子Adpn、Fndc 5、Angptl 8、IL-6和Rbp 4，然后用IPA软件进行分析。提取大鼠BAT总蛋白，Western blot检测PRDM 16、PGC 1 α、PPARγ、PPARα、SIRT 1、ChREBP、AMPKα、UCP 1、ADPN、NRG 4、GLUT 1和GLUT 4。GQD组Pparγc1α、Pparα、Pparγ、Ucp 1、Cidea、Ampkα2、Dio 2、Fndc 5、Rbp 4、Angpt 18 mRNA表达水平较糖尿病组显著升高（P<0.05），Adpn、IL-6 mRNA表达水平较糖尿病组显著降低（P<0.05）。GQD组Sirt 1表达呈下降趋势（P=0.104），Prdm 16表达呈上调趋势（P=0.182）。IPA经典途径分析和疾病功能分析表明，GQD通过激活PPARα/RXRα和SIRT 1信号通路，促进BAT分化，减少脂质过度积累。糖尿病组PRDM 16、PGC 1 α、PPARα、PPARγ、SIRT 1、ChREBP、AMPKα、UCP 1、GLUT 1、GLUT 4和NRG 4蛋白表达水平均显著降低（P<0. 01），经GQD干预后，上述蛋白表达水平均显著升高（P<0. 05）。糖尿病组ADPN蛋白表达较正常对照组明显上调（P<0.01），GQD治疗组ADPN蛋白表达较正常对照组明显下调（P<0.01）。本研究表明，GQD促进BAT分化成熟，增加能量消耗，从而减少糖脂代谢紊乱，从而改善糖尿病症状。
This study explored the molecular mechanism underlying the Gegen Qinlian Decoction(GQD) promoting the differentiation of brown adipose tissue(BAT) to improve glucose and lipid metabolism disorders in diabetic rats. After the hypoglycemic effect of GQD on diabetic rats induced by high-fat diet combined with a low dose of streptozotocin was confirmed, the total RNA of rat BAT around scapula was extracted. Nuclear transcription genes Prdm16, Pparγc1α, Pparα, Pparγ and Sirt1, BAT marker genes Ucp1, Cidea and Dio2, energy expenditure gene Ampkα2 as well as BAT secretion factors Adpn, Fndc5, Angptl8, IL-6 and Rbp4 were detected by qPCR, then were analyzed by IPA software. Afterward, the total protein from rat BAT was extracted, and PRDM16, PGC1α, PPARγ, PPARα, SIRT1, ChREBP, AMPKα, UCP1, ADPN, NRG4, GLUT1 and GLUT4 were detected by Western blot. The mRNA expression levels of Pparγc1α, Pparα, Pparγ, Ucp1, Cidea, Ampkα2, Dio2, Fndc5, Rbp4 and Angptl8 were significantly increased(P<0.05) and those of Adpn and IL-6 were significantly decreased(P<0.05) in the GQD group compared with the diabetic group. In addition, Sirt1 showed a downward trend(P=0.104), whereas Prdm16 tended to be up-regulated(P=0.182) in the GQD group. IPA canonical pathway analysis and diseases-and-functions analysis suggested that GQD activated PPARα/RXRα and SIRT1 signaling pathways to promote the differentiation of BAT and reduce the excessive lipid accumulation. Moreover, the protein expression levels of PRDM16, PGC1α, PPARα, PPARγ, SIRT1, ChREBP, AMPKα, UCP1, GLUT1, GLUT4 and NRG4 were significantly decreased in the diabetic group(P<0.01), which were elevated after GQD intervention(P<0.05). Unexpectedly, the expression of ADPN protein in the diabetic group was up-regulated(P<0.01) as compared with the control group, which was down-regulated after the administration with GQD(P<0.01). This study indicated that GQD promoted BAT differentiation and maturity to increase energy consumption, which reduced the glucose and lipid metabolism disorders and thereby improved diabetes symptoms.