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淫羊藿苷改善糖尿病小鼠血管功能的作用及其机制

王喜鸟, 姚文慧, 潘珍珍, 董洁炎, 刘硕, 丁选胜

王喜鸟, 姚文慧, 潘珍珍, 董洁炎, 刘硕, 丁选胜. 淫羊藿苷改善糖尿病小鼠血管功能的作用及其机制[J]. 中国药科大学学报, 2022, 53(2): 215-221. DOI: 10.11665/j.issn.1000-5048.20220212
引用本文: 王喜鸟, 姚文慧, 潘珍珍, 董洁炎, 刘硕, 丁选胜. 淫羊藿苷改善糖尿病小鼠血管功能的作用及其机制[J]. 中国药科大学学报, 2022, 53(2): 215-221. DOI: 10.11665/j.issn.1000-5048.20220212
WANG Xiniao, YAO Wenhui, PAN Zhenzhen, DONG Jieyan, LIU Shuo, DING Xuansheng. Protective effects and mechanism of icariin against vascular function in diabetic mice[J]. Journal of China Pharmaceutical University, 2022, 53(2): 215-221. DOI: 10.11665/j.issn.1000-5048.20220212
Citation: WANG Xiniao, YAO Wenhui, PAN Zhenzhen, DONG Jieyan, LIU Shuo, DING Xuansheng. Protective effects and mechanism of icariin against vascular function in diabetic mice[J]. Journal of China Pharmaceutical University, 2022, 53(2): 215-221. DOI: 10.11665/j.issn.1000-5048.20220212

淫羊藿苷改善糖尿病小鼠血管功能的作用及其机制

基金项目: 国家科技重大专项重大新药创制资助项目(No.2017ZX09301004);国家自然科学基金资助项目(No.81873131)

Protective effects and mechanism of icariin against vascular function in diabetic mice

Funds: This study was supported by the National Science and Technology Major Project-Major New Drug Innovation Foundation (No.2017ZX09301004) and the National Natural Science Foundation of China (No.81873131)
  • 摘要: 为探讨淫羊藿苷(icariin,ICA)对四氧嘧啶诱导的糖尿病小鼠血管舒缩功能的影响及其分子机制,采用腹腔注射200 mg/kg四氧嘧啶的方法诱导1型糖尿病小鼠模型,连续14 d灌胃给予60,120 mg/kg ICA后,考察药物对糖尿病模型小鼠血糖、体重、摄食量、饮水量的影响;分离各组小鼠的胸主动脉并检测其对乙酰胆碱(acetylcholine,Ach)、硝普钠(sodium nitroprusside,SNP)诱导的血管环舒张反应和对苯肾上腺素(phenylephrine,Phe)、KCl诱导的血管环收缩反应,以评价ICA对各组小鼠离体胸主动脉血管环舒缩功能的影响。为进一步探讨ICA改善血管功能的机制,采用高糖(35 mmol/L)诱导人脐静脉内皮细胞(HUVECs)建立细胞模型,Western blot法检测ICA对高糖诱导的HUVECs中eNOS、p-eNOS、p38 MAPK和p-p38 MAPK蛋白表达的影响。结果显示,ICA显著改善糖尿病小鼠的体重下降和饮水量增多,对摄食量、血糖有一定改善作用,但无统计学差异。离体胸主动脉血管环舒缩功能实验结果显示,ICA显著改善糖尿病小鼠胸主动脉环对Phe诱导的血管环收缩和对Ach诱导的内皮依赖性血管环舒张,对KCl诱导的血管环收缩反应有一定改善但无显著性差异,对SNP诱导的非内皮依赖性血管环舒张无显著影响。Western blot实验结果显示,ICA显著抑制高糖诱导的HUVECs中p-p38 MAPK表达,促进eNOS的磷酸化激活。以上结果提示ICA可能通过抑制p-p38 MAPK表达,促进eNOS磷酸化激活,从而改善四氧嘧啶诱导的糖尿病小鼠的血管内皮舒缩功能。
    Abstract: To explore the effects and molecular mechanism of icariin on the vascular function of mice with type 1 diabetes induced by alloxan, type 1 diabetic mice model was established by intraperitoneal injection with 200 mg/kg alloxan.After oral administration with icariin (60, 120 mg/kg) daily for 2 weeks, blood glucose, body weight, food intake and water intake were detected.To evaluate the impact of icariin on the function of isolated vascular ring contraction and relaxation, thoracic aortas of mice were removed and the Ach-induced vascular ring relaxation, Phe-induced vascular ring contraction, SNP-induced vascular ring relaxation and KCl-induced vascular ring contraction response were detected.To further confirm the mechanism of icariin to improve vascular function, human umbilical vein endothelial cells (HUVECs) were induced by high glucose (HG) in vitro.Western blot was used to detect the effect of icariin on eNOS, p-eNOS, p38 MAPK and p-p38 MAPK expressions in HG-induced human umbilical vein endothelial cells (HUVECs).The results indicated that icariin significantly ameliorated the weight loss and dampened the increase in water intake of the diabetic mice.Meanwhile, icariin had a certain ameliorative effect on blood glucose and food intake without significant difference.The results of isolated thoracic aortas vascular rings contraction and vasodilation function indicated that icariin significantly improved Phe-induced vascular contraction and Ach‐induced vascular relaxation.Meanwhile, icariin had a certain ameliorative effect on KCl-induced vascular contraction response without significant difference.However, no significant change was observed on endothelium‐independent vascular rings relaxation response induced by SNP after treatment with icariin.Results of Western blot showed that icariin inhibited the expression of p-p38 MAPK and induced expression of p-eNOS in the high glucose-induced HUVECs cell model.Therefore, icariin may attenuate alloxan-induced type 1 diabetic mice vascular diastolic function by inhibiting expression of p-p38 MAPK and inducing expression of p-eNOS.
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出版历程
  • 收稿日期:  2021-10-17
  • 修回日期:  2022-03-08
  • 刊出日期:  2022-04-24

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