天香丹对动脉粥样硬化模型小鼠TLR4/NF-κB信号通路的影响Effects of Tianxiang Dan on TLR4/NF-κB Signaling Pathway in Atherosclerosis Model Mice
张华,苗文艳,徐正伟,叶成辉,安冬青
摘要(Abstract):
目的 通过研究天香丹对动脉粥样硬化(AS)模型小鼠Toll样受体-4(TLR4)/核因子-κB(NF-κB)信号通路及相关炎症因子的影响,探讨天香丹防治AS的可能机制。方法 选取8周龄ApoE-/-小鼠30只予以高脂饲料喂养12周,造模成功后随机分为模型组、他汀组、天香丹组,每组10只;另取10只C57BL/6J小鼠予以普通饲料喂养作为空白对照组。他汀组、天香丹组分别以相应药液3 mg/kg、2.7 g/kg灌胃干预,空白组、模型组以0.5 mL蒸馏水灌胃,每日1次,连续12周。取小鼠血清用于检测血脂水平及TLR4、NF-κB、肿瘤坏死因子-α(TNF-α)含量,取主动脉用于观察主动脉病理变化情况。结果 1)HE染色结果显示:他汀组、天香丹组病理改变较模型组轻,斑块稳定性提高,模型组主动脉斑块面积(PA)与管腔面积(LA)比值显著大于空白组(P <0.01),他汀组、天香丹组PA/LA比值则小于模型组(P <0.01)。2)血脂检测结果显示:较空白组,模型组三酰甘油(TAG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)明显升高,高密度脂蛋白胆固醇(HDL-C)明显降低(P <0.01);与模型组比较,他汀组、天香丹组TAG及TC降低明显(P <0.01),天香丹组HDL-C升高(P <0.01)、LDL-C降低(P <0.01)。3)ELISA结果显示:模型组血清中TLR4、NF-κB、TNF-α含量均高于空白组(P <0.01),他汀组、天香丹组血清中TLR4、NF-κB、TNF-α含量均低于模型组(P <0.01)。结论 天香丹具有防治AS的作用,其机制可能与调控TLR4/NF-κB信号通路、抑制炎症反应有关。
关键词(KeyWords): 动脉粥样硬化;天香丹;Toll样受体-4;核因子-κB;小鼠
基金项目(Foundation): 新疆维吾尔自治区卫生健康青年医学科技人才专项(WJWY-202235);; 新疆维吾尔自治区自然科学基金(2021D01F60)
作者(Author): 张华,苗文艳,徐正伟,叶成辉,安冬青
参考文献(References):
- [1] Virani SS,Alonso A,Benjamin EJ,et al. Heart disease and stroke statistics-2020 update:a report from the american heart association[J]. Circulation,2020,141(9):e139-e596.
- [2] Libby P. Inflammation in atherosclerosis-no longer a theory[J]. Clin Chem,2021,67(1):131-142.
- [3] ZHU Y,XIANG X,WANG Z,et al. Research progress on the relationship between atherosclerosis and inflammation[J].Biomolecules,2018,8(3):80-91.
- [4] LIU T,ZHANG L,Joo D,et al. NF-kappaB signaling in inflammation[J]. Signal Transduct Target Ther,2017,23(2):e17023-e17032.
- [5] ZHONG L,Simard MJ,Huot J. Endothelial microRNAs regulating the NF-kappaB pathway and cell adhesion molecules during inflammation[J]. FASEB J,2018,32(8):4070-4084.
- [6]欧思琳,李茹冰. NF-κB在动脉粥样硬化疾病中的研究进展[J].中国免疫学杂志,2018,34(7):1095-1101.
- [7] Yusuf S,Bosch J,Dagenais G,et al. Cholesterol lowering in intermediate-risk persons without cardiovascular disease[J].N Engl J Med,2016,374(21):2021-2031.
- [8] Lonn EM,Bosch J,Lopez Jaramillo P,et al. Blood-pressure lowering in intermediate-risk persons without cardiovascular disease[J]. N Engl J Med,2016,374(21):2009-2020.
- [9] Yusuf S,Lonn E,Pais P,et al. Blood-pressure and cholesterol lowering in persons without cardiovascular disease[J]. N Engl J Med,2016,374(21):2032-2043.
- [10]孙龙飞,徐风燕,安冬青.天香丹治疗冠状动脉粥样硬化性心脏病秽浊痰阻证患者的临床疗效观察[J].中华中医药杂志,2021,36(11):6912-6916.
- [11]张华,马学宽,王思静,等.芳香新塔花对动脉粥样硬化模型小鼠Tol样受体-4/核因子-κB信号通路的影响[J].中国循环杂志,2020,35(4):395-400.
- [12]马文慧,安冬青.天香丹对动脉粥样硬化秽浊痰阻证ApoE-/-小鼠的实验研究[J].中国中医急症,2015,24(3):377-379.
- [13]张华,王思静,安冬青.天香丹治疗冠心病的研究进展[J].中西医结合心脑血管病杂志,2019,17(17):2601-2603.
- [14] SUN LF,AN DQ,Niyazi GL,et al. Effects of tianxiangdan granule treatment on atherosclerosis via NFkappaB and p38MAPK signaling pathways[J]. Mol Med Rep,2018,17(1):1642-1650.
- [15]徐叔云,卞如濂,陈修.药理学实验方法[M].北京:人民卫生出版社,2002:3.
- [16] Molinero LL,Alegre ML. Role of T cell-NF-κB in transplantation[J]. Trans-plantation Reviews,2012,26(3):189-200.
- [17] LI LC,Varghese Z,Moorhead JF,et al. Cross-talk between TLR4-MyD88-NF-κB and SCAP-SREBP2 pathways mediates macrophage foam cell formation[J]. Am J Physiol Heart Circ Physiol,2013,304(6):H874-H884.
- [18] ZHOU P,Hwang KW,Palucki DA,et al. Impaired NF-κB activation in T cells permits tolerance to primary heart allografts and to secondary donor skin grafts[J]. American Journal of Transplantation Official Journal of the American Society of Transplantation&the American Society of Transplant Surgeons,2015,3(2):139-147.
- [19] LIU N,LIU JT,JI YY,et al. C-reactive protein triggers inflammatory responses partly via TLR4/IRF3/NF-κB signaling pathway in rat vascular smooth muscle cells[J]. Life Sciences,2010,87(11-12):367-374.