齐墩果酸对糖尿病大鼠心肌保护作用及机制研究  

The protective effect of oleanolic acid on diabetic myocardium of rats and its mechanism

作　　者：孙波[1] 张晓晓[1] 刘廪 朱江[1] 谢红[1] Sun Bo;Zhang Xiaoxiao;Liu Lin;Zhu Jiang;Xie Hong(Department of Anesthesiology,Second Affiliated Hospital,Soochow University,Suzhou 215004,China)

机构地区：[1]苏州大学附属第二医院麻醉科,215004

出　　处：《中华急诊医学杂志》2020年第9期1191-1195,共5页Chinese Journal of Emergency Medicine

基　　金：国家自然科学基金面上项目(81372024)。

摘　　要：目的观察研究齐墩果酸(oleanolic acid,OA)对糖尿病心肌病(diabetic cardiomyopathy,DCM)大鼠心脏的保护作用及其机制。方法50只健康4周龄雄性SD大鼠随机(随机数字法)分为正常对照组(CON)、糖尿病组(DM)、糖尿病+齐墩果酸组(DM+OA)、糖尿病+氯喹(chloroquine,CQ)组(DM+CQ)和糖尿病+齐墩果酸+氯喹组(DM+OA+CQ),每组10只。通过喂食高脂高糖食物(质量百分比35.5%)和腹腔注射链脲霉素建立糖尿病动物模型。OA 80 mg/(kg·d)灌胃喂药4周,CQ 10 mg/(kg·d)腹腔注射4周。于20周后进行超声心功能检测后麻醉取大鼠心脏组织。采用超声心动图检测SD大鼠心脏功能,并通过Western blot技术对自噬相关蛋白LAMP2、p-ULK1、p-p70S6K、p-raptor、LC3、p62进行蛋白半定量分析,观察大鼠心功能及心肌细胞中自噬相关蛋白表达的变化。正态分布计量资料多组间比较采用单因素方差分析,组间两两比较采用SNK-q检验。结果与CON组相比,DM组大鼠心脏舒张末期心肌前壁厚度、左室舒张末期容积、左室收缩末期容积[(7.58±0.25)mm、(376.6±13.6)μL、(132.6±10.8)μL]低于CON组[(8.37±0.11)mm、(458.3±16.4)μL、(166.6±12.8)μL](均P<0.05)。与DM组比较,DM+OA组大鼠心脏舒张末期心肌前壁厚度、左室舒张末期容积、左室收缩末期容积[(8.63±0.14)mm、(473.6±18.6)μL、(174.6±12.7)μL]高于DM组(均P<0.05)。DM+OA+CQ组大鼠心脏舒张末期心肌前壁厚度、左室舒张末期容积、左室收缩末期容积[(7.97±0.17)mm、(393.6±15.6)μL、(147.6±10.2)μL]低于DM+OA组(均P<0.05)。DM组心肌细胞自噬相关蛋白p-ULK1表达升高、p-p70S6K及p-raptor表达降低(均P<0.05)。与DM组比较,OA治疗组心脏功能障碍减轻,伴随p62表达降低、LC3Ⅱ/Ⅰ表达升高(均P<0.05)。与DM+CQ组比较,DM+OA+CQ组p62表达降低,LC3Ⅱ/Ⅰ表达升高(均P<0.05)。结论OA对糖尿病大鼠的心肌具有保护作用,其机制可能与增强自噬有关。objective To investigate the protective effect of oleanolic acid(OA)on the heart of diabetic cardiomyopathy(DCM)rats and its mechanism.Methods Fifty healthy 4-week-old male SD rats were randomly(random number)divided into the normal control group(CON),diabetes mellitus group(DM),diabetes mellitus+oleanolic acid group(DM+OA),diabetes mellitus+chloroquine group(DM+CQ)and diabetes mellitus+oleanolic acid+chloroquine group(DM+OA+CQ),with 10 rats in each group.The diabetic animal model was established by feeding high-fat and high-sugar food(35.5%wt/wt),intra-abdominal injection of streptozotocin(STZ)50 mg/kg 4 weeks later,and feeding highfat and high-sugar food for another 16 weeks.OA was orally administered at 80 mg/(kg·d)for 4 weeks,and CQ was intraperitoneal injected at 10 mg/kg per day for 4 weeks.The rats were anesthetized after echocardiographic examination at the end of the 20th week.Echocardiography was used to detect the heart function of SD rats,and the autophagy related proteins LAMP2,p-ULK1,p-p70s6k,p-raptor,LC3 and p62 were semi-quantitatively analyzed by Western blot.Changes in cardiac function and expression of autophagy related proteins in cardiac myocytes of rats were observed.One-way analysis of variance was used for comparison among groups of normally distributed measurement data,SNK-q test was used for pairwise comparison between two groups.Results Compared with the CON group,the end diastolic wall thickness,left ventricular end diastolic volume,and end left ventricular systolic volume[(7.58±0.25)mm,(376.6±13.6)μL,and(132.6±10.8)μL]of the DM group were lower than those of the CON group[(8.37±0.11)mm,(458.3±16.4)μL,and(166.6±12.8)μL](all P<0.05).Compared with the DM group,the end diastolic wall thickness,left ventricular end diastolic volume,and left ventricular end systolic volume[(8.63±0.14)mm,(473.6±18.6)μL,and(174.6±12.7)μL]of the DM+OA group were higher than those of the DM group(all P<0.05).The anterior wall thickness,left ventricular end-diastolic volume,and left ventricular e

关 键 词：糖尿病心肌病 齐墩果酸 自噬 心功能 溶酶体 大鼠 

分 类 号：R587.2[医药卫生—内分泌] R542.2[医药卫生—内科学]