丹酚酸B改善糖尿病血糖波动模型大鼠心肌损伤的作用  

Effect of salvianolic acid B on improving myocardium injury in diabetic rats with blood glucose fluctuation

作　　者：赵梦秋 任尤楠 陶善珺 郑书国[2] Zhao Mengqiu;Ren Younan;Tao Shanjun;Zheng Shuguo(Department of Pharmacy,Anhui Health College,Chizhou 247009,China;Department of Pharmacology,Wannan Medical College,Wuhu 241002,China)

机构地区：[1]安徽卫生健康职业学院药学教研室,安徽池州247009 [2]皖南医学院药理学教研室,安徽芜湖241002

出　　处：《山东第一医科大学（山东省医学科学院）学报》2021年第5期369-374,共6页Journal of Shandong First Medical University ＆ Shandong Academy of Medical Sciences

基　　金：国家自然科学基金(81102626);安徽高校省级自然科学研究重点项目(KJ2019A1283);安徽省级教学团队(2018jxtd072)。

摘　　要：目的观察丹酚酸B(salvianolic acid B,Sal B)对糖尿病血糖波动模型大鼠心肌损伤的改善作用,并探讨其可能机制。方法采用高糖高脂饮食合并腹腔注射链脲佐菌素(STZ)的方法建立大鼠糖尿病模型,在此基础上通过错时给予胰岛素或葡萄糖建立糖尿病血糖波动模型,治疗组分别给予丹酚酸B 160 mg/kg和80 mg/kg。6周后,检测大鼠血糖水平,HE染色法观察大鼠心肌组织病理学改变,ELISA法检测心肌组织白介素-1β(IL-1β)、白介素-18(IL-18)、天冬氨酸特异的半胱氨酸蛋白酶1(Caspase-1)以及血清白介素-6(IL-6)、乳酸脱氢酶(LDH)水平,比色法检测心肌组织总抗氧化能力(TAC),Western blot法检测心肌组织核转录因子-κB(NF-κB)活化、核苷酸结合寡聚化结构域样受体蛋白-3(NLRP3)蛋白表达水平。结果丹酚酸B降低糖尿病血糖波动模型大鼠空腹血糖(P<0.05),减轻心肌损伤,提高心肌组织抗氧化能力(P<0.01)。丹酚酸B降低糖尿病大鼠LDH、IL-6、IL-1β、IL-18水平(P<0.01),抑制NF-κB活化、NLRP3蛋白表达及Caspase-1水平(P<0.05或P<0.01)。结论丹酚酸B能够改善糖尿病血糖波动模型大鼠心肌损伤,其机制可能与抑制NF-κB/NLRP3/Caspase-1通路,改善心肌炎症状态有关。Objective:To investigate the improvement effect of salvianolic acid B(Sal B)on myocardial injury in diabetic rats with blood glucose fluctuation and the possible mechanisms implicated.Methods:Diabetes rat model was induced by streptozotocin(STZ)plus high fat and high sugar diet.All the rats except those in control group were subjected to intraperitoneal injection of insulin or intragastric administration of glucose at indicated time to induce blood glucose fluctuation,while those in Sal B groups were supplemented intragastrically with sal B 160 mg/kg and 80 mg/kg,respectively.Six weeks later,fasting blood glucose(FBG)and levels of mean daily blood glucose(MBG),standard deviation of blood glucose(SDBG),largest amplitude of glycemic excursion(LAGE)were collected to measure the stability of blood glucose.The primary histopathological changes of myocardium tissue were observed by HE staining.Serum levels of interleukin-6(IL-6)and lactic dehydrogenase(LDH)and myocardial contents of interleukin-1β(IL-1β),interleukin-18(IL-18)and cysteine aspartic acid specific protease-1(Caspase-1)were evaluated by ELISA.Total anti-oxidant capacity(TAC)of myocardium tissue was determined with commercially available kits.Protein levels of nuclear factor-κB(NF-κB)and NOD-like receptor 3(NLRP3)in myocardium tissue were examined by Western blotting analysis.Results:After 6 weeks of blood glucose fluctuation,FBG,MBG,SDBG and LAGE of diabetic rats were all increased more significantly than those in control group(P<0.01).Treatment with salvianolic acid B reduced level of FBG(P<0.05).Compared with the model group,treatment with sal B evidently ameliorated pathological changes of myocardium,accompanied by a significant increase of total antioxidant capacity(P<0.01),as well as decrease in levels of LDH,IL-6,IL-1βand IL-18(P<0.05 or P<0.01).Sal B markedly down-regulated NF-κB nuclear translocation,protein expression of NLRP3 and activity of Caspase-1 in myocardium tissue(P<0.05 or P<0.01).Conclusion:Treatment with sal B can evidently amelio

关 键 词：丹酚酸B 糖尿病 血糖波动 心肌损伤 炎症 

分 类 号：R965[医药卫生—药理学]