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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

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、LC3 Ⅱ/Ⅰ表达升高(均 P<0.05)。与DM+CQ组比较,DM+OA+CQ组p62表达降低,LC3 Ⅱ/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。

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abstracts:

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 high-fat 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 end-systolic volume [(7.97± 0.17) mm, (393.6±15.6) μL, and (147.6±10.2) μL] of the DM+OA+CQ group were lower than those of the DM+OA group (all P<0.05). The expression of autophagy-related protein p-ULK1 was increased and the expression of p-p70s6k and p-raptor was decreased in the DM group (all P<0.05). Compared with the DM group, cardiac dysfunction was reduced in the OA group, accompanied by decreased p62 expression and increased LC3Ⅱ/Ⅰ expression (both P<0.05). Compared with the DM+CQ group, p62 expression was decreased and LC3 Ⅱ/Ⅰ expression was increased in the DM+OA+CQ group (both P<0.05). Conclusions:OA has a protective effect on the myocardium of diabetic rats, which may be related to enhanced autophagy.

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作者: 孙波 [1] 张晓晓 [1] 刘廪 [1] 朱江 [1] 谢红 [1]
期刊: 《中华急诊医学杂志》2020年29卷9期 1191-1195页 ISTICPKUCSCDCA
栏目名称: 基础研究
DOI: 10.3760/cma.j.issn.1671-0282.2020.09.010
发布时间: 2020-11-09
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