达格列净对慢性心力衰竭大鼠心肌细胞基质金属蛋白酶及其组织抑制因子-1水平的影响  

Effects of dapagliflozin on expressions of matrix metalloproteinases and tissue inhibitors of metalloproteinase-1 in myocardial tissues of rats with chronic heart failure

作　　者：杨薪 蔡学坤[1] 吴泽龙[1] 黄兆琦[2] YANG Xin;CAI Xue-kun;WU Ze-long;HUANG Zhao-qi(Department of Geriatrics,The Third Affiliated Hospital of Guangzhou Medical University,Guangzhou 510150,Guangzhou Province,China;Department of Cardiology,The Third Affiliated Hospital of Guangzhou Medical University,Guangzhou 510150,Guangzhou Province,China)

机构地区：[1]广州医科大学附属第三医院老年医学科,广东广州510150 [2]广州医科大学附属第三医院心血管内科,广东广州510150

出　　处：《中国临床药理学杂志》2023年第8期1104-1107,共4页The Chinese Journal of Clinical Pharmacology

摘　　要：目的探讨达格列净对慢性心衰大鼠心肌细胞基质金属蛋白酶-2(MMP-2)、MMP-9及其组织抑制因子-1(TIMP-1)表达的影响。方法以腹主动脉缩窄(AC)法建立慢性心力衰竭大鼠模型。将50只雄性SD大鼠随机分成假手术组、假手术+达格列净组、模型组、模型+达格列净组。假手术+达格列净组和模型+达格列净组予以每天1次喂养达格列净1 mg·kg^(-1),喂养8周。以Masson染色法观察心肌组织胶原纤维;以酸水解法检测心肌组织羟脯氨酸并计算胶原总含量;以实时荧光定量聚合酶链反应检测各组心肌组织MMP-2、MMP-9、TIMP-1表达情况。结果假手术组、假手术+达格列净组、模型组、模型+达格列净组大鼠心肌组织胶原容积分数分别为(2.01±0.43)%、(1.98±0.80)%、(4.61±0.52)%和(3.48±0.74)%;羟脯氨酸含量分别为(0.27±0.06)、(0.25±0.08)、(0.63±0.05)和(0.47±0.10)μg·mg^(-1);胶原总含量分别为(2.05±0.21)、(2.01±0.41)、(4.70±0.32)和(3.51±0.27)μg·mg^(-1);心肌组织MMP-2表达水平分别为1.00±0.00、0.98±0.12、2.57±0.28和1.65±0.16;MMP-9表达水平分别为1.00±0.00、0.99±0.06、2.76±0.22和1.81±0.18;TIMP-1表达水平分别为1.00±0.00、1.07±0.08、0.63±0.17和0.81±0.20。模型组、模型+达格列净组的上述指标与假手术组比较,差异均有统计学意义(均P<0.05);模型+达格列净组的上述指标与模型组比较,差异均有统计学意义(均P<0.05)。结论达格列净可能通过调节MMPs/TIMP-1通路参与慢性心力衰竭心肌纤维化的调控,减轻心肌纤维化,延缓心室重塑和心衰的进展,改善慢性心力衰竭的预后。Objective To observe the effects of dapagliflozin on the expressions of metalloproteinase-2(MMP-2),metalloproteinase-9(MMP-9)and tissue inhibitors of metalloproteinase-1(TIMP-1)in myocardial tissues of rats with chronic heart failure.Methods The heart failure model was established by abdominal aorta coarctation(AC).Fifty male SD rats were randomly divided into the sham group,the sham+dapagliflozin group,the model group and the model+dapagliflozin group.Rats in the sham+dapagliflozin group and the model+dapagliflozin group were treated by dapagliflozin(1 mg·kg^(-1))for eight we eks.Myocardial collagen fibers were evaluated through Masson staining;the contents of hydroxyproline(HYP)were measured by acid hydrolysis methods and the total collagen in myocardium was tested;the mRNA expressions of MMP-2,MMP-9 and TIMP-1 in myocardial tissues were detected by real-time fluorescence quantitative polymerase chain reaction.Results The collagen volume fraction levels in the sham group,the sham+dapagliflozin group,the model group and the model+dapagliflozin group were(2.01±0.43)%,(1.98±0.80)%,(4.61±0.52)%and(3.48±0.74)%;the HYP levels in the four groups were(0.27±0.06),(0.25±0.08),(0.63±0.05)and(0.47±0.10)μg·mg^(-1);the total collagen contents were(2.05±0.21),(2.01±0.41),(4.70±0.32)and(3.51±0.27)μg·mg^(-1);the mRNA expressions of MMP-2 were 1.00±0.00,0.98±0.12,2.57±0.28 and 1.65±0.16;the mRNA expressions of MMP-9 were 1.00±0.00,0.99±0.06,2.76±0.22 and 1.81±0.18;the mRNA expressions of TIMP-1 were 1.00±0.00,1.07±0.08,0.63±0.17 and 0.81±0.20,respectively.Compared with the sham group,the above indexes in the model group and the model+dapagliflozin group were statistically significant(all P<0.05);the above indexes in the model+dapagliflozin group were statistically significant compared with those of model group(all P<0.05).Conclusion Dapagliflozin can regulate the expressions of MMPs/TIMP-1 in myocardial tissue of rats with chronic heart failure,which may be the important mechanism in delaying the myo

关 键 词：达格列净 心力衰竭 基质金属蛋白酶-2 基质金属蛋白酶-9 组织抑制因子-1 

分 类 号：R541[医药卫生—心血管疾病]