探讨茶黄素-3,3'-O-双没食子酸酯（TFDG）对糖尿病大鼠血管内皮损伤及炎症反应的保护作用及相关机制。以高脂饲料喂养加链脲佐菌素注射制造糖尿病大鼠,将其分为模型组（CON）、5 mg·kg-1和10 mg·kg-1 TFDG干预组（TFDG5和TFDG10）,另取正常大鼠为对照组（NC）,分组处理8周,监测体重和空腹血糖变化,观察大鼠腹主动脉病理形态学变化,ELISA检测血浆IL-6、IL-1β和TNF-α水平,Western blot检测蛋白表达水平。结果表明,与CON组相比,TFDG干预对体重和血糖无显著影响,病理切片观察显示TFDG干预组大鼠腹主动脉组织损伤较CON组有所改善,同时TFDG干预组大鼠血浆炎症因子水平显著降低,血浆NO水平显著升高,腹主动脉组织MDA水平降低。进一步研究显示,TFDG下调了糖尿病大鼠腹主动脉组织NLRP3、caspase-1和IL-1β的表达,抑制NLRP3炎症通路激活。TFDG能够有效保护糖尿病大鼠血管内皮损伤并抑制炎症反应,其机制可能是通过下调NLRP3炎症通路实现的。
Abstract
To investigate the protective effect and mechanism of theaflavin-3,3'-O-digallate (TFDG) on vascular endothelial injury and inflammation in rats with diabetes mellitus, diabetic rats were made by high fat feed and streptozotocin injection and then divided into model group (CON), 5 mg·kg-1 and 10 mg·kg-1 TFDG intervention group (TFDG5 and TFDG10). The normal rats were taken as control group (NC). After 8 weeks of treatment, the pathological changes of abdominal aorta were observed. Plasma IL-6, IL-1β and TNF-α were detected by ELISA. The protein expression was detected by Western blot. Compared with CON, TFDG administration has no significant effects on body weight and fasting blood glucose. Pathological sections show that the injury of aorta tissue in TFDG group was improved compared with that in CON group. At the same time, the level of plasma inflammatory factors was significantly decreased, the level of plasma NO was significantly increased, and the level of MDA in aorta tissue was decreased in TFDG group. Further studies show that TFDG could down-regulate NLRP3, caspase-1 and IL-1β expressions in the aorta of diabetic rats. TFDG effectively protected vascular endothelial injury and inhibit inflammatory response in diabetic rats, and its mechanism might be through down-regulation of NLRP3 inflammatory pathway.
关键词
茶黄素 /
糖尿病 /
血管内皮损伤 /
炎症反应
Key words
diabetes mellitus /
inflammatory response /
theaflavin /
vascular endothelial injury
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参考文献
[1] Li Y Z, Teng D, Shi X G, et al.Prevalence of diabetes recorded in mainland China using 2018 diagnostic criteria from the American Diabetes Association: national cross sectional study[J]. British Medical Journal, 2020, 369: m997. doi: 10.1136/bmj.m997.
[2] Calvo-Maroto A M, Esteve-Taboada J J, Pérez-Cambrodí RJ, et al. Pilot study on visual function and fundus autofluorescence assessment in diabetic patients[J]. Journal of Ophthalmology, 2016, 2016: 1287847. doi:10.1155/2016/1287847.
[3] 许咏梅, 施云峰. 中国红茶出口“一带一路”沿线国家贸易及其影响因素实证分析[J]. 茶叶科学, 2019, 39(5): 602-610.
Xu Y M, Shi Y F.An empirical analysis of the trade and influencing factors of China's black tea export to countries along the Belt and Road[J]. Journal of Tea Science, 2019, 39(5): 602-610.
[4] 王洪新, 孙军涛, 吕文平, 等. 茶黄素的制备、分析、分离及功能活性研究进展[J]. 食品与生物技术学报, 2011, 30(1): 12-19.
Wang H X, Sun J T, Lv W P, et al.Research progress on preparation, analysis, separation and funtion of theaflavins[J]. Journal of Food Science and Biotechnology, 2011, 30(1): 12-19.
[5] He H F.Research progress on theaflavins: efficacy, formation, and preparation[J]. Food & Nutrition Research, 2017, 61(1): 1344521. doi: 10.1080/16546628.2017.1344521.
[6] Lin Y L, Tsai S H, Lin-Shiau S Y, et al. Theaflavin-3,3'-digallate from black tea blocks the nitric oxide synthase by down-regulating the activation of NF-кB in macrophages[J]. European Journal of Pharmacology, 1999, 367(2/3): 379-388.
[7] 雷时成, 孙大利, 王亚洁, 等. 茶黄素双没食子酸酯的生物活性及其作用机制[J]. 食品与机械, 2020, 36(2): 229-236.
Lei S C, Sun D L, Wang Y J, et al.Biological activities of theaflavin-3,3'-digallate and its mechanism of action[J]. Food & Machinery, 2020, 36(2): 229-236.
[8] Ogurtsova K, da Rocha Fernandes J D, Huang Y, et al. IDF Diabetes Atlas: global estimates for the prevalence of diabetes for 2015 and 2040[J]. Diabetes Research and Clinical Practice, 2017, 128: 40-50.
[9] Simmons R K, Griffin S J, Lauritzen T, et al.Effect of screening for type 2 diabetes on risk of cardiovascular disease and mortality: a controlled trial among 139,075 individuals diagnosed with diabetes in Denmark between 2001 and 2009[J]. Diabetologia, 2017, 60(11): 2192-2199.
[10] Tancredi M, Rosengren A, Svensson A M, et al.Excess mortality among persons with type 2 diabetes[J]. The New England Journal of Medicine, 2015, 373(18): 1720-1732.
[11] Cull C A, Jensen C C, Retnakaran R, et al.Impact of the metabolic syndrome on macrovascular and microvascular outcomes in type 2 diabetes mellitus: United Kingdom prospective diabetes study 78[J]. Circulation, 2007, 116(19): 2119-2126.
[12] Zhang J, Chen J, Yang J, et al.Resveratrol attenuates oxidative stress induced by balloon injury in the rat carotid artery through actions on the ERK1/2 and NF-KappaB pathway[J]. Cellular Physiology & Biochemistry, 2013, 31(2/3): 230-241.
[13] Ben Lagha A, Grenier D.Black tea theaflavins attenuate porphyromonas gingivalis virulence properties, modulate gingival keratinocyte tight junction integrity and exert anti-inflammatory activity[J]. Journal of Periodontal Research, 2017, 52(3): 458-470.
[14] Tan Q, Peng L, Huang Y, et al.Structure-activity relationship analysis on antioxidant and anticancer actions of theaflavins on human colon cancer cells[J]. Journal of Agricultural and Food Chemistry, 2019, 67(1): 159-170.
[15] Duewell P, Kono H, Rayner K J, et al.NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals[J]. Nature, 2010, 464(7306): 1357-1361.
[16] Jin Y, Fu J.Novel insights into the NLRP3 inflammasome in atherosclerosis[J]. Journal of the American Heart Association, 2019, 8(12): e012219. doi: 10.1161/jaha.119.012219.
[17] Jin C, Flavell R A.Molecular mechanism of NLRP3 inflammasome activation[J]. Journal of Clinical Immunology, 2010, 30(5): 628-631.
[18] Eisenbarth S C, Colegio O R, O'Connor W, et al. Crucial role for the Nalp3 inflammasome in the immunostimulatory properties of aluminium adjuvants[J]. Nature, 2008, 453(7198): 1122-1126.
[19] Zhao J, Wang Z, Yuan Z, et al.Baicalin ameliorates atherosclerosis by inhibiting NLRP3 inflammasome in apolipoprotein E-deficient mice[J]. Diabetes & Vascular Disease Research, 2020, 17(6): 1479164120977441. doi: 10.1177/1479164120977441.
[20] Wang R, Wang Y, Mu N, et al.Activation of NLRP3 inflammasomes contributes to hyperhomocysteinemia-aggravated inflammation and atherosclerosis in apoE-deficient mice[J]. Laboratory Investigation, 2017, 97(8): 922-934.
[21] Du R H, Tan J, Sun X Y, et al. Fluoxetine inhibits NLRP3 inflammasome activation: implication in depression [J]. International Journal of Neuropsychopharmacology, 2016, 19(9): pyw037. doi: 10.1093/ijnp/pyw037.
基金
西南大学全面提升研究生教育质量工程项目（XYDS201905）
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