|
|
枸杞多糖通过生物节律基因Clock和Bmal1调节小鼠脂质代谢
|
Abstract:
目的：探究枸杞多糖通过调节生物节律基因(Clock, Bmal1)的变化来影响小鼠脂质代谢。方法：选用C57BL/6J雄性小鼠建立肥胖小鼠模型，不同剂量枸杞多糖进行干预。检测小鼠血清学指标总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)；利用苏木素伊红(HE)染色法进行肝脏组织形态学观察。利用蛋白免疫印记杂交(Western blot)检测Clock蛋白、Bmal1蛋白的表达水平。结果：血清学指标示：实验组TG、LDL及HDL水平与模型组相比均有显著性差异。HE染色结果显示：在肝脏的组织切片中，模型组中肝细胞出现大量的脂滴。枸杞多糖低剂量组、中剂量组和高剂量组肝细胞脂肪变的情况有不同程度改善。Western blot检测结果显示：在模型组中生物节律基因Clock和Bmal1的表达有所下降，在枸杞多糖干预组中Clock和Bmal1的表达有所上调。结论：枸杞多糖能够改善肥胖小鼠脂质的异常代谢，其机制可能是通过调节小鼠生物节律基因Clock和Bmal1的表达水平来实现的。
Objective: To investigate the effect of LBP on lipid metabolism in mice by regulating changes in biorhythmic genes (Clock, Bmal1). Methods: C57BL/6J male mice were selected to establish an obese mouse model, and different doses of LBP were used for drug intervention. Total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) were detected as serological indicators in mice. Liver histomorphometry was performed using hematoxylin eosin (HE) staining. The expression levels of Clock protein and Bmal1 protein were detected using Western blot (WB) hybridization for protein immunoblotting. Results: Serological indices showed that TG, LDL, HDL levels in the experimental group were all significantly different compared to the model group. The results of HE staining showed that in the tissue sections of the liver, a large number of lipid droplets appeared in the hepatocytes in the model group. Hepatocyte steatosis was improved to different degrees in the LBP low-dose, medium-dose and high-dose groups. The results of Western blot assay showed that the expression of biorhythm genes Clock and Bmal1 decreased in the model group, and the expression of Clock and Bmal1 was up-regulated in the LBP intervention group. Conclusion: LBP can improve the abnormal metabolism of lipids in obese mice, and its mechanism may be realized by regulating the expression levels of mouse biorhythm genes Clock and Bmal1.
| [1] | 张彦康, 张婷, 李雨, 等. 肥胖治疗的挑战与希望[J]. 自然杂志, 2022, 44(6): 469-479. |
| [2] | 高璐璐, 杨建军. 枸杞多糖对高脂饮食诱导的非酒精性脂肪肝大鼠的保护作用及对肠道菌群的影响[C]//营养研究与临床实践——第十四届全国营养科学大会暨第十一届亚太临床营养大会、第二届全球华人营养科学家大会论文摘要汇编. 2019: 495-496. |
| [3] | 杨捷, 刘子龙, 高玉雯, 等. 似昼夜节律与糖脂代谢的研究进展[J]. 空军军医大学学报, 2022: 1-10. |
| [4] | 张玮芸, Chi-tang Ho, 吕慕雯. 基于脂质组学研究胡椒碱对肥胖大鼠脂代谢基因昼夜节律的影响[J]. 食品科学, 2023: 1-13. |
| [5] | 中国超重/肥胖医学营养治疗指南(2021) [J]. 中国医学前沿杂志(电子版), 2021, 13(11): 1-55. |
| [6] | 庞文琪, 钱帅伟, 李春艳, 等. 社会时差与肥胖和糖尿病关系研究进展[J]. 中国糖尿病杂志, 2022, 30(9): 695-699. |
| [7] | 高扬, 杨婷婷, 于亮. 时钟基因Bmal1: 白色脂肪棕色化的重要调控点[J]. 中国运动医学杂志, 2023, 42(6): 493-500. |
| [8] | 陈江慧, 周玫余, 黄荣凤, 等. 进食节律差异调节棕色脂肪组织的生物钟与代谢基因昼夜节律[J]. 生理学报, 2022, 74(5): 726-736. |
| [9] | 邢陈, 顾晔, 宋伦. 昼夜节律在代谢调控中的作用[J]. 军事医学, 2017, 41(7): 618-622. |
| [10] | 郁珽, 李晓南. 生物钟与肥胖[J]. 中国儿童保健杂志, 2018, 26(12): 1327-1331. |
| [11] | 吴礼邦. 昼夜颠倒进食对高脂肥胖小鼠脂肪组织脂代谢及节律的研究[D]: [硕士学位论文]. 武汉: 武汉轻工大学, 2022. |
| [12] | 张敏, 岳坤, 姜交华, 等. 枸杞子及其有效成分的药理作用研究进展[J]. 药物评价研究, 2023, 46(7): 1611-1619. |
| [13] | 宋育林, 曾民德, 陆伦根, 等. 枸杞多糖对高脂饮食诱导的脂肪肝大鼠模型的影响[J]. 安徽医药, 2007(3): 202-205. |
| [14] | 张民, 肖军霞, 施春雷, 等. 枸杞多糖-4对下丘脑损伤性肥胖小鼠减肥作用的探讨[J]. 营养学报, 2003(2): 196-199. |
| [15] | 陈紫蕙, 王惠琴. 肥胖高血压患者血清半胱氨酸天冬氨酸蛋白水解酶1和含NLR家族Pyrin域蛋白3与血压昼夜节律的关系[J]. 中华高血压杂志, 2023, 31(10): 985-989. |
| [16] | 张正敏, 曹洪战, 芦春莲, 等. 生物钟对动物糖脂代谢的影响研究进展[J]. 中国畜牧杂志, 2020, 56(1): 30-34. |
| [17] | Shigeki, S., Norimasa, I., Yuki, O., et al. (2005) Brain and Muscle Arnt-Like Protein-1 (BMAL1), a Component of the Molecular Clock, Regulates Adipogenesis. Proceedings of the National Academy of Sciences of the United States of America, 102, 12071-12076. https://doi.org/10.1073/pnas.0502383102 |
| [18] | Hepler, C., Weidemann, B.-J., Waldeck, N.-J., et al. (2022) Time-Restricted Feeding Mitigates Obesity through Adipocyte Thermogenesis. Science (New York, N.Y.), 378, 276-284. https://doi.org/10.1126/science.abl8007 |
| [19] | Feldmann, H.M., Golozoubova, V., Cannon, B. and Nedergaard, J. (2009) UCP1 Ablation Induces Obesity and Abolishes Diet-Induced Thermogenesis in Mice Exempt from Thermal Stress by Living at Thermoneutrality. Cell Metabolism, 9, 203-209. https://doi.org/10.1016/j.cmet.2008.12.014 |
| [20] | Hasan, N., Nagata, N., Morishige, J.-I., et al. (2021) Brown Adipocyte-Specific Knockout of Bmal1 Causes Mild but Significant Thermogenesis Impairment in Mice. Molecular Metabolism, 49, Article ID: 101202.
https://doi.org/10.1016/j.molmet.2021.101202 |
| [21] | Tong, X., Zhang, D.Q., Arthurs, B., et al. (2015) Palmitate Inhibits SIRT1-Dependent BMAL1/CLOCK Interaction and Disrupts Circadian Gene Oscillations in Hepatocytes. PLOS ONE, 10, e0130047.
https://doi.org/10.1371/journal.pone.0130047 |
| [22] | Pekovic-vaughan, V., Gibbs, J., Yoshitane, H., et al. (2014) The Circadian Clock Regulates Rhythmic Activation of the NRF2/Glutathione-Mediated Antioxidant Defense Pathway to Modulate Pulmonary Fibrosis. Genes & Development, 28, 548-560. https://doi.org/10.1101/gad.237081.113 |
| [23] | 陈少影, 李晶晶, 兰卫. 常用中药有效成分降脂作用研究进展[J]. 中国实验方剂学杂志, 2023, 29(13): 241-253. |
