葛根芩连汤对高脂诱导肝脏胰岛素抵抗小鼠SIRT1/FoxO1信号通路的影响

隋淼; 陈国芳; 茅晓东; 韦晓; 吴波; 黄慧; 范尧夫; 刘超

葛根芩连汤对高脂诱导肝脏胰岛素抵抗小鼠SIRT1/FoxO1信号通路的影响

隋淼^1,2,
陈国芳³,
茅晓东³,
韦晓³,
吴波¹,
黄慧¹,
范尧夫^3,,
刘超^3,

1.
南京中医药大学第三临床医学院，江苏南京 210028
2.
南京中医药大学附属徐州市中医院，江苏徐州 221009
3.
南京中医药大学附属中西医结合医院，江苏南京 210028

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出版历程
- 刊出日期: 2018-11-10

The Mechanism Exploration of Gegen Qinlian Decoction on Hepatic Insulin Resistance Through SIRT1/FoxO1 Pathway

1.
The Third Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, 210028, China
2.
Xuzhou City Hospital of TCM Affiliated to Nanjing University of Chinese Medicine, Xuzhou, 221009, China
3.
Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, China

摘要

摘要: 目的研究葛根芩连汤对高脂诱导胰岛素抵抗小鼠SIRT1/FoxO1信号通路的影响，探讨其在改善肝脏胰岛素抵抗的效果和作用机制。方法雄性C57BL/6J小鼠成模后，分为正常组，高脂模型组，葛根芩连汤高、低剂量组，吡格列酮组及联合用药组。正常组和高脂模型组予等体积的灭菌水，其余各组予对应药物，连续灌胃8周。期间观察小鼠体质量、血糖、甘油三酯，并计算HOMA-IR变化情况；肝脏组织HE染色，评估脂质沉积情况；Western blot检测SIRT1/FoxO1信号通路中各蛋白表达程度；qPCR检测肝脏组织SIRT1、FoxO1的mRNA的表达。结果同高脂模型组相比，葛根芩连汤各剂量组小鼠的体质量、甘油三酯、胰岛素水平及HOMA-IR均显著降低（P<0.01）；肝脏病理切片显示，葛根芩连汤各剂量组和吡格列酮组肝脏空泡变性明显降低；葛根芩连汤各剂量组及吡格列酮组SIRT1 mRNA表达较高脂模型组明显增加（P<0.05）；与正常对照组相比，高脂模型组SIRT1、PPARγ蛋白表达水平明显降低（P<0.05~0.01），acely-FoxO1、FABP4蛋白表达水平升高（P<0.01），药物干预后，各组SIRT1、PPARγ蛋白表达水平明显升高（P<0.05~0.01），acely-FoxO1、FABP4蛋白表达降低（P<0.05~0.01）。结论葛根芩连汤可以通过上调SIRT1表达，减少FoxO1乙酰化水平，改善肝脏胰岛素抵抗。
- 葛根芩连汤 /
- 胰岛素抵抗 /
- SIRT1/FoxO1信号通路
Abstract: OBJECTIVE To study the influence of Gegen Qinlian Decoction (GGQLD) on SIRT1/FoxO1 signaling pathway in high-fat-induced insulin resistance mice and its mechanism in improving hepatic insulin resistance. METHODS Except those in the normal group， male C57BL/6J mice with insulin resistance were established by feeding high fat diet. Then mice were randomly divided into five groups: high fat diet group， and the four groups treated with low dose of GGQLD， high dose of GGQLD， positive medicine (Pioglitazone)， GGQLD combined with Pioglitazone， respectively. The control group was given equal volume of sterilized water， and the others were given corresponding drugs for 8 weeks. Animals were examined for weight gain， blood glucose and triglyceride. HOMA-IR was calculated. The lipid deposition in liver tissue was detected by HE staining. The protein expression of SIRT1/FoxO1 signaling pathway were detected by Western blot. SIRT1 and FoxO1 mRNA expression were detected by qPCR. RESULTS Compared with the high fat diet group， the body weight， triglyceride， insulin level and HOMA-IR of each group were significantly lower (P<0.01). Liver pathology showed that the liver vacuolation of various doses of Gegen Qinlian Decoction groups and pioglitazone group decreased significantly. The mRNA expression of SIRT1 in these treatment groups were higher than those in the high fat diet group (P<0.05). Compared with the control group， the protein expression of SIRT1 and PPARγ in the high fat diet group was significantly decreased (P<0.05， P<0.01) and the protein expression of acely-FoxO1 and FABP4 increased (P<0.01). After treatment， the protein expression of SIRT1 and PPARγ increased significantly (P<0.05， P<0.01)， and the protein expression of acely-FoxO1 and FABP4 decreased (P<0.05， P<0.01). CONCLUSION Gegen Qinlian Decoction can inhibit acely-FoxO1 and improve hepatic insulin resistance by activating SIRT1/FoxO1 signaling pathway.
- Gegen Qinlian Decoction /
- insulin resistance /
- SIRT1/FoxO1 signaling pathway

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参考文献(9)

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