青蒿素及其衍生物对糖尿病小鼠血糖及炎症因子的影响

Effects of artemisinin and its derivatives on the blood glucose and inflammatory factors in db/db mice

摘要:

目的： 探讨青蒿素及青蒿素衍生物对糖尿病小鼠血糖、体质量及炎症因子表达的影响。方法： 正常对照组为4~6周龄健康db/m小鼠5只，顺应性喂养；实验组为4~6周龄健康db/db小鼠20只，随机分为4组：安慰剂组、青蒿素组、蒿甲醚组、青蒿琥酯组，每组5只。安慰剂组每天给予羟甲基纤维素灌胃，干预组分别给予青蒿素[200 mg/（kg·d）]、蒿甲醚[200 mg/（kg·d）]、青蒿琥酯[200 mg/（kg·d）]灌胃，共干预10周。每周测1次小鼠体质量及空腹血糖，每2周测1次随机血糖。取小鼠血清，ELISA检测血清中炎症因子：细胞间黏附分子-1（intercellular adhesion molecule-1，ICAM-1/CD54）、白介素（interleukin，IL）-6、IL-8、细胞瘦素（leptin，LEP）、核因子-κB（nuclear factor kappa B，NF-κB）、IL-1β水平变化。结果： ①与db/m组相比，安慰剂组db/db小鼠空腹及随机血糖明显升高。与安慰剂组相比，青蒿素、蒿甲醚及青蒿琥酯组小鼠空腹及随机血糖明显降低。②与db/m组相比，db/db组小鼠体质量明显增加。与安慰剂相比，青蒿素可以明显降低糖尿病小鼠体质量，而蒿甲醚、青蒿琥酯对糖尿病小鼠无明显减重作用。③与db/m组相比，安慰剂组db/db小鼠的炎症因子ICAM-1/CD54、IL-6、IL-8、LEP、NF-κB、IL-1β水平均升高。与安慰剂相比，青蒿素、蒿甲醚和青蒿琥酯明显降低糖尿病小鼠炎症因子ICAM-1/CD54、IL-6、IL-8、LEP、NF-κB、IL-1β水平。比较而言，青蒿琥酯抗炎能力最强，炎症因子水平明显降低，青蒿素次之，蒿甲醚抗炎能力相对较弱。结论： 青蒿素、蒿甲醚及青蒿琥酯可以明显降低糖尿病小鼠血糖和炎症因子的表达，且青蒿素可以减轻糖尿病小鼠体质量，而蒿甲醚和青蒿琥酯无明显减重作用。综合来看，青蒿素具有减重降糖作用，治疗效果更为显著。

Abstract:

Objective: To investigate the effects of artemisinin and its derivatives on blood glucose, body weight and expression of inflammatory factors in db/db mice. Methods: Five healthy db/m mice aged 4-6 weeks were collected as the normal control group with responsive feeding. Twenty db/db mice were randomized into four groups: the placebo group, the artemisinin group, the artemether group and the artesunate group, with five mice in each group. The placebo group was administrated with hydroxymethylcellulose daily, and the intervention group was administrated with artemisinin[200 mg/ (kg·d)], artemether[200 mg/ (kg·d)] and artesunate[200 mg/ (kg·d)] for 10 weeks. The body weight and fasting blood glucose of mice were measured once a week, and the random blood glucose was measured every two weeks. The changes of inflammatory factors in serum were detected by ELISA, including intercellular adhesion molecule-1 (ICAM-1/CD54), interleukin-6 (IL-6), interleukin-8 (IL-8), leptin (LEP), nuclear factor kappa B (NF-κB) and interleukin-1β (IL-1β). Results: Firstly, compared with db/m group, fasting blood glucose and random blood glucose were all significantly higher in db/db group. Compared with placebo group, the fasting and random blood glucose in artemisinin, artemether and artesunate group decreased significantly. Secondly, compared with db/m group, the body weight of db/db group increased significantly. Compared with placebo, artemisinin could significantly reduce the weight of diabetic mice, while artemether and artesunate had no significant weight loss effect on diabetic mice. Thirdly, compared with db/m group, the levels of ICAM-1/CD54, IL-6, IL-8, LEP, NF-κB and IL-1β in db/db group were all increased. Compared with placebo, artemisinin, artemetherandartesunatesignificantly reduced the levels of ICAM-1/CD54, IL-6, IL-8, LEP, NF-κB and IL-1β in diabetic mice. In comparison, artesunate had the strongest anti-inflammatory ability, and the level of inflammatory factors was reduced significantly, followed by artemisinin, and artemether had relatively weak anti-inflammatory ability. Conclusion: Artemisinin and its derivatives, artemether and artesunate, could significantly reduce the expression of blood glucose and inflammatory factors in db/db mice. Artemisinin can reduce the body weight of db/db mice, but artemether and artesunate have no obvious effect on body weight. In conclusion, artemisinin has the best therapeutic effect on diabetic mice.