髓样分化蛋白-2调控AMPK介导肥胖所致心肌损伤的研究  

Medullary differentiation-2 mediates obesity-induced myocardial injury by regulating adenosine AMPK

作　　者：黄成坷[1] 周伶俐[2] 孙未[1] 林晓东 陈瑞杰[1] HUANG Cheng-ke;ZHOU Ling-li;SUN Wei;LIN Xiao-dong;CHEN Rui-jie(Department of Pharmacy,The Second Afiliated Hospital of Wenzhou Medical University,Wenzhou 325027,Zhejiang Province,China;Department of Pathology,The Second Afiliated Hospital of Wenzhou Medical University,Wenzhou 325027,Zhejiang Province,China)

机构地区：[1]温州医科大学附属第二医院药学部,浙江温州325027 [2]温州医科大学附属第二医院病理科,浙江温州325027

出　　处：《中国临床药理学杂志》2024年第10期1458-1462,共5页The Chinese Journal of Clinical Pharmacology

基　　金：温州市科技计划基金资助项目(Y2020969)。

摘　　要：目的探讨髓样分化蛋白-2(MD-2)通过调控AMP依赖的蛋白激酶(AMPK)介导肥胖引起的心肌损伤中的作用。方法用高脂饲料喂养制备肥胖小鼠模型。将野生型和MD-2基因敲除小鼠随机分为野生型对照组(正常饲养)、野生型模型组(高脂饲料)、敲除对照组(正常饲养)和敲除模型组(高脂饲料),每组8只。用试剂盒测定血清肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)水平,用小动物超声检测左心室射血分数(LVEF)和左短轴缩短率(LVFS),用苏木精-伊红(HE)染色法和Masson染色法观察心肌组织病理变化,用蛋白质印迹法检测心肌组织中磷酸化AMPK(p-AMPK)蛋白的表达情况。结果HE染色和Masson染色结果发现野生型模型组小鼠心肌组织出现明显变性坏死和纤维化,而敲除模型组心肌细胞变性坏死与心肌组织纤维化明显减轻。野生型对照组、野生型模型组、敲除对照组和敲除模型组的LVEF值分别为(83.98±7.58)%、(52.03±4.91)%、(76.42±3.89)%和(73.71±4.22)%,LVFS值分别为(53.61±8.51)%、(24.56±3.76)%、(48.14±5.00)%和(44.07±3.74)%,CK-MB值分别为(49.83±15.49)、(83.75±11.90)、(54.03±18.66)和(66.85±12.98)U·L^(-1),LDH值分别为(12.24±3.20)、(27.90±6.10)、(13.55±3.55)和(15.53±2.58)U·L^(-1),p-AMPK蛋白相对表达水平分别为221.31±88.76、46.29±10.07、148.66±32.02和161.49±78.11。野生型模型组的上述指标与野生型对照组比较,敲除模型组的上述指标与野生型模型组比较,在统计学上差异均有统计学意义(均P<0.05)。结论高脂饲料通过MD-2抑制AMPK活性介导了肥胖小鼠的心肌损伤。Objective To investigate the effects of medullary differentiation-2(MD-2)in obesity-induced myocardial injury by regulating adenosine 5'-monophosphate-activated protein kinase(AMPK)activity.Methods The obese mice model was established by feeding high-fat feed.The wild-type and MD-2 gene knockout mice were randomly divided into wild-type(WT)-control group(fed normally),WT-model group(fed with high-fat diet),knockout(KO)-control group(fed normally)and KO-model group(fed with high-fat diet)with 8 mice in each group.At week 16,creatine kinase-MB(CK-MB)and lactate dehydrogenase(LDH)were measured by reagent kits;the left ventricular ejection fraction(LVEF)and left ventricular fraction shortening(LVFS)were measured with ultrasonic apparatus;the pathological changes in myocardial tissue were observed by hematoxylin and eosin(HE)staining and Masson staining;the protein expression of phosphorylation AMPK(p-AMPK)was measured by Western blot.Results HE staining and Masson staining results revealed significant necrosis and fibrosis of the myocardial tissue in WT-model group,while the degrees of necrosis and fibrosis in KO-model group were significantly reduced.The LVEF values of the WT-control group,WT-model group,K0-control group and KO-model group were(83.98±7.58)%,(52.03±4.91)%,(76.42±3.89)%and(73.71±4.22)%,respectively;the LVFS values of each group were(53.61±8.51)%,(24.56±3.76)%,(48.14±5.00)%and(44.07±3.74)%,respectively;the CK-MB values of each group were(49.83±15.49),(83.75±11.90),(54.03±18.66)and(66.85±12.98)U·L^(-1),respectively;the LDH values of each group were(12.24±3.20),(27.90±6.10),(13.55±3.55)and(15.53±2.58)U·L^(-1),respectively;the relative expression levels of p-AMPK in each group were 221.31±88.76,46.29±10.07,148.66±32.02 and 161.49±78.11.Compared with WT-control group,the above indicators in WT-model group,compared with WT-model group,the above indicators in KO-model group,the differences were statistically significant(all P<0.05).Conclusion MD-2 mediates high-fat feed induced myocardi

关 键 词：髓样分化蛋白-2 AMP依赖的蛋白激酶 肥胖 心肌损伤 

分 类 号：R97[医药卫生—药品]