青蒿琥酯对糖尿病大鼠MEK/ERK通路及心肌纤维化的影响  

Effects of Artesunate on MEK/ERK Pathway and Myocardial Fibrosis in Diabetic Rats

作　　者：杨萍 代天 刘波 邹勇 赵谦 张苏川 YANG Ping;DAI Tian;LIU Bo;ZOU Yong;ZHAO Qian;ZHANG Suchuan(Affiliated Hospital of Jianghan University,Wuhan Sixth Hospital,Wuhan 430015,Hubei,China)

机构地区：[1]江汉大学附属医院/武汉市第六医院,武汉430015

出　　处：《中西医结合心脑血管病杂志》2023年第9期1610-1614,共5页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

基　　金：武汉市中医药科研项目(No.WZ22Z03)。

摘　　要：目的:探索青蒿琥酯对糖尿病大鼠丝裂原细胞外信号调节激酶(MEK)/细胞外信号调节激酶(ERK)通路及心肌纤维化的影响。方法:制作糖尿病大鼠模型,随机分为模型组、青蒿琥酯低剂量(25 mg/kg)组、青蒿琥酯中剂量(50 mg/kg)组、青蒿琥酯高剂量(100 mg/kg)组、二甲双胍(70 mg/kg)组,每组12只,另取12只SD大鼠设为对照组。分组处理后,测定大鼠血糖、总胆固醇(TC)及三酰甘油(TG)水平;Masson染色检测大鼠心肌组织纤维化情况;酶联免疫吸附法(ELISA)检测大鼠血清肌酸激酶同工酶(CK-MB)、肌钙蛋白I(cTnI)、肿瘤坏死因子-α(TNF-α)及白细胞介素-6(IL-6)水平;蛋白免疫印迹法检测心肌组织MEK/ERK通路相关蛋白表达。结果:与对照组比较,模型组大鼠心肌呈现明显纤维化变性,大鼠血糖、TC、TG、CK-MB、cTnI、TNF-α、IL-6水平及心肌组织MEK/ERK通路蛋白p-MEK/MEK、p-ERK/ERK明显升高(P<0.05)。与模型组比较,青蒿琥酯低剂量组、青蒿琥酯中剂量组、青蒿琥酯高剂量组及二甲双胍组大鼠心肌组织纤维化程度减轻,且纤维化程度随青蒿琥酯剂量增加而逐渐递减,血糖、TC、TG、CK-MB、cTnI、TNF-α、IL-6水平及心肌组织MEK/ERK通路蛋白p-MEK/MEK、p-ERK/ERK降低(P<0.05),且青蒿琥酯各组呈剂量依赖性,青蒿琥酯高剂量组与二甲双胍组比较,各指标比较差异无统计学意义(P>0.05)。结论:青蒿琥酯可抑制MEK/ERK通路激活,修复糖脂代谢紊乱,减轻心肌组织炎症损伤,缓解其纤维化变性。Objective:To explore the effects of artesunate on mitogen extracellular signal regulated kinase(MEK)/extracellular signal-regulated kinase(ERK)pathway and myocardial fibrosis in diabetic rats.Methods:Diabetic rat model was established,and the rats were randomly divided into model group,low-dose artesunate group(25 mg/kg),middle dose artesunate group(50 mg/kg),high-dose artesunate group(100 mg/kg),metformin group(70 mg/kg),with 12 rats in each group,and another 12 SD rats were selected as control group.After treatment,the levels of blood glucose,total cholesterol(TC),and triglyceride(TG)were measured.Masson staining was used to detect myocardial fibrosis.The levels of serum creatine kinase MB(CK-MB),troponin I(cTnI),tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6)were detected by enzyme-linked immunosorbent assay.The expression of MEK/ERK pathway protein was detected by Western Blot.Results:Compared with control group,myocardial fibrosis was obvious in model group,and the blood glucose,TC,TG,serum CK-MB,cTnI,TNF-α,and IL-6 levels,phosphorylation-MEK(p-MEK)/MEK and phosphorylation-ERK(p-ERK)/ERK in model group were significantly increased(P<0.05).Compared with model group,the degree of myocardial fibrosis in low-dose artesunate group,middle dose artesunate group,high-dose artesunate group,and metformin group was reduced,and the degree of fibrosis was gradually decreased with the increase of artesunate dose.Compared with model group,the levels of blood glucose,TC,TG,CK-MB,cTnI,TNF-α,IL-6,p-MEK/MEK,and p-ERK/ERK in low-dose artesunate group,middle dose artesunate group,high-dose artesunate group,and metformin group was decreased in a dose-dependent manner(P<0.05).There was no significant difference in each index between high-dose artesunate group and metformin group.Conclusion:Artesunate can inhibit the activation of MEK/ERK pathway,repair the disorder of glucose and lipid metabolism,reduce myocardial inflammatory damage,and alleviate myocardial fibrosis.

关 键 词：糖尿病 青蒿琥酯 丝裂原细胞外信号调节激酶/细胞外信号调节激酶通路 心肌纤维化 肿瘤坏死因子-α 白细胞介素-6 实验研究 

分 类 号：R285.5[医药卫生—中药学]