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尿石素A改善糖尿病小鼠心肌损伤的作用机制研究

Effect and mechanism of urolithin A on cardiomyopathy injury in diabetic mice
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摘要 目的观察植物多酚鞣花酸代谢产物尿石素A对2型糖尿病小鼠心肌损伤的保护作用及其可能的作用机制。方法雄性c57BL/6小鼠饲以高脂饲料联合腹腔注射链脲佐菌素建立2型糖尿病模型。按照体重将造模成功小鼠随机分为2组:模型组,实验组,每组10只。正常组和模型组灌胃给予等量蒸馏水;实验组按50 mg·kg^(-1)·d^(-1)剂量灌胃给予尿石素A,连续给药7周。蛋白质印迹法测定心脏组织裂解的半胱氨酸蛋白酶3(cleaved-caspase3)、细胞自噬相关蛋白微管相关蛋白轻链3(LC3Ⅱ/Ⅰ)及选择性自噬接头蛋白(p62)蛋白表达(灰度值比值)。结果正常组、模型组和实验组的cleaved-caspase3蛋白相对表达量为1.00±0.18,7.37±0.72和5.76±0.56;LC3Ⅱ/Ⅰ蛋白相对表达量为1.00±0.14,0.36±0.09和0.51±0.07;p62的蛋白相对表达量为1.00±0.09,3.22±0.18和2.64±0.15。上述指标:模型组与正常组比较,差异均有统计学意义(P<0.05或P<0.01);实验组与模型组比较,差异均有统计学意义(P<0.05或P<0.01)。结论尿石素A对糖尿病小鼠心肌具有保护作用,可能与抑制心肌细胞凋亡、激活自噬有关。 Objective To observe the protective effect of plant polyphenol ellagic acid metabolite urolithin A(UA)on cardiomyopathy injury in type 2 diabetic mice,and to explore its possible mechanism of action.Methods Male c57 BL/6 mice were fed with high-fat diet and combined with streptozocin(STZ)intraperitoneal injection to establish type 2 diabetes model.Successful mice model were randomly divided into two group according to weight:experimental group and model group,10 mice in each group.Another normal mice was as normal group.Mice in normal group and model group were given the same amount of distilled water,the experimental group was given 50 mg·kg^(-1)UA,for 7 weeks.Western blot was used to determine the protein expression(ration of gray value)of cleaved-caspase3,autophagy-related microtubule-related protein light chain 3(LC3Ⅱ/Ⅰ)and selective autophagy adaptor protein(p62)in diabetic mice heart.Results The level of cleaved-caspase3 protein in the normal group,model group,experimental group were 1.00±0.18,7.37±0.72,5.76±0.56,respectively;the level of LC3Ⅱ/Ⅰprotein in the three groups were 1.00±0.14,0.36±0.09,0.51±0.07,respectively;the level of p62 protein in the three groups were 1.00±0.09,3.22±0.18,2.64±0.15,respectively.Comparison between model group and normal group,the difference of the factors were significant(P<0.05 or P<0.01);comparison between experimental group and model group,the difference of the factors were significant(P<0.05 or P<0.01).Conclusion UA has a protective effect on the heart of diabetic mice,which may be related to the inhibition of cardiomyocyte apoptosis and activation of autophagy.
作者 张䶮之 王艳勃 古丽海夏·哈勒玛合拜 张晓莹 张婷婷 贺宇轩 马丽 ZHANG Yan-zhi;WANG Yan-bo;GULIHAIXIA·Halem ahebai;ZHANG Xiao-ying;ZHANG Ting-ting;HE Yu-xuan;MA Li(Department of Pharmacology,School of Pharmacy,Xinjiang Medical University,Urumqi 830011,Xinjiang Uyghur Autonomous Region,China;The Fifth Clinical Medicine College,Xinjiang Medical University,Urumqi 830011,Xinjiang Uyghur Autonomous Region,China)
出处 《中国临床药理学杂志》 CAS CSCD 北大核心 2021年第9期1070-1073,共4页 The Chinese Journal of Clinical Pharmacology
基金 国家自然科学基金资助项目(81760767) 新疆维吾尔自治区“十三五”重点学科建设专项经费支持基金资助项目 新疆维吾尔自治区自然科学基金资助项目(2017D01C204) 新疆医科大学博士启动基金资助项目(2019-17) 新疆医科大学大学生创新基金资助项目(CX2018027) 新疆自治区大学生创新基金资助项目(201810760027)。
关键词 尿石素A 糖尿病心肌病 裂解的半胱氨酸蛋白酶3 自噬 urolithin A diabetic cardiomyopathy cleaved-caspase 3 autophagy
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