欢迎访问《中国实验方剂学杂志》编辑部网站!
抵挡汤对糖尿病大血管病变小鼠主动脉NLRP3炎症小体活化炎症级联反应的作用机制
作者:
作者单位:

1.天津医科大学 朱宪彝纪念医院,天津市内分泌研究所,国家卫健委激素与发育重点实验室, 天津市代谢性疾病重点实验室,天津 300314;2.中国中医科学院 望京医院,北京 100102

作者简介:

傅红敏,在读硕士,从事中西医结合治疗糖尿病研究,E-mail:varesmile@163.com

通讯作者:

常柏,博士生导师,主任医师,从事糖尿病大血管病变有关课题研究,E-mail:changbai1972@126.com

中图分类号:

R2-0;R22;R285.5;R289;R33

基金项目:

国家自然科学基金项目(81973614)


Mechanism of Didangtang in Inhibiting Aortic NLRP3 Inflammasome Cascade of Mice with Diabetic Macrovascular Disease
Author:
Affiliation:

1.Tianjin Medical University Chu Hsien-I Memorial Hospital,Tianjin Institute of Endocrinology,NHC Key Laboratory of Hormones and Development,Tianjin Institute of Endocrinology,Tianjin 300314,China;2.Wangjing Hospital,China Academy of Chinese Medical Sciences,Beijing 100102,China

Fund Project:

  • 摘要
  • |
  • 图/表
  • |
  • 访问统计
  • |
  • 参考文献
  • |
  • 相似文献
  • |
  • 引证文献
  • |
  • 资源附件
  • |
  • 文章评论
    摘要:

    目的 观察糖尿病大血管病变进程,探讨不同剂量抵挡汤对糖尿病大血管病变的影响。方法 选取4周龄雄性载脂蛋白E敲除(ApoE-/-)小鼠,采用高脂喂养联合链脲佐菌素(STZ)诱导制备糖尿病大血管病变模型,并随机分为模型组、抵挡汤高、中、低剂量组和辛伐他汀组;并以同批次同周龄ApoE-/-小鼠仅高脂喂养,作为ApoE-/-组;取相同遗传背景的C57BL/6小鼠常规喂养作为正常组。分别于实验第8,20周取材。观察不同时期各组小鼠主动脉病理特点及斑块面积占比,比较各组小鼠血糖、血脂、氧化低密度脂蛋白(ox-LDL)水平,蛋白免疫印迹法(Western blot)检测主动脉NOD样受体3(NLRP3),半胱氨酸天冬氨酸蛋白酶-1(Caspase-1)蛋白表达,酶联免疫吸附测定法(ELISA)检测血清中白细胞介素-1β(IL-1β),白细胞介素-18(IL-18),白细胞介素-1α(IL-1α),肿瘤坏死因子-α(TNF-α)炎症因子。结果 与正常组比较,ApoE-/-组、模型组内斑块占比显著增高(P<0.01),与模型组比较,各给药组能明显降低血管内斑块占比(P<0.05);与正常组比较,ApoE-/-组、模型组主动脉NLRP3,Caspase-1蛋白表达水平显著升高(P<0.01),血清中IL-1β,IL-18,IL-1α,TNF-α显著升高(P<0.01),与模型组比较,各给药组能够明显抑制主动脉NLRP3,Caspase-1蛋白的表达,降低血清中IL-1β,IL-18,IL-1α,TNF-α等炎症因子水平(P<0.05),且以中剂量组抑制作用最强(P<0.05)。结论 抵挡汤能独立于降糖、降脂之外改善糖尿病大血管病变,这可能与下调NLRP3,Caspase-1蛋白表达,减轻炎症级联反应相关。

    Abstract:

    Objective To explore the progression of diabetic macrovascular disease and the effects of Didangtang at different doses on it.Method Four-week-old male apolipoprotein-E knockout (ApoE-/-) mice with diabetic macrovascular disease induced by exposure to high-fat diet combined with streptozotocin (STZ) were randomly divided into the model, simvastatin, as well as high-, medium-, and low-dose Didangtang groups. The age-matched ApoE-/- mice of the same batch only fed with a high-fat diet were classified into the ApoE-/- (model control) group, and C57BL/6 mice with the same genetic background receiving a regular diet into the normal group. The sampling was conducted at the 8th and 20th weeks of the experiment for observing the pathological characteristics of the aorta and the proportion of plaque area in mice of each group at different time points, followed by the comparison of blood glucose, blood lipid, and oxidized low-density lipoprotein (ox-LDL) levels. The aortic NOD-like receptor protein 3 (NLRP3) and cysteinyl aspartate-specific proteinase-1 (Caspase-1) protein expression was detected by Western blot assay, and the serum interleukin-1β (IL-1β), interleukin-18 (IL-18), interleukin-1α (IL-1α), and tumor necrosis factor-α (TNF-α) levels by enzyme-linked immunosorbent assay (ELISA).Result The comparison with the normal group revealed that the proportions of plaque area in the ApoE-/- group and the model group were increased (P<0.01), while the proportion of plaque area in each administration group was significantly reduced in contrast to that of the model group (P<0.05). The aortic NLRP3 and Caspase-1 protein expression levels as well as the serum IL-1β, IL-18, IL-1α, and TNF-α levels in the ApoE-/- group and the model group were significantly higher than those in the normal group (P<0.01). Compared with the model group, each administration group exhibited a significant reduction in aortic NLRP3 and Caspase-1 protein expression and serum IL-1β, IL-18, IL-1α, and TNF-α levels (P<0.05), with the strongest inhibitory effect detected in the medium-dose Didangtang group (P<0.05).Conclusion Didangtang directly alleviates diabetic macrovascular disease possibly by down-regulating NLRP3 and Caspase-1 protein expression and easing the inflammatory cascade.

    参考文献
    相似文献
    引证文献
引用本文

傅红敏,任秋月,常柏.抵挡汤对糖尿病大血管病变小鼠主动脉NLRP3炎症小体活化炎症级联反应的作用机制[J].中国实验方剂学杂志,2021,27(11):1~8

复制
分享
文章指标
  • 点击次数:
  • 下载次数:
  • HTML阅读次数:
  • 引用次数:
历史
  • 收稿日期:2021-02-07
  • 最后修改日期:
  • 录用日期:
  • 在线发布日期: 2021-05-06
  • 出版日期:

地址:北京东直门内南小街16号

邮编:100700

电话:010-84076882

E-mail:syfjx_2010@188.com

中国实验方剂学杂志 ® 2021 版权所有

技术支持:北京勤云科技发展有限公司