摘要
目的探讨罗格列酮对糖尿病心肌病(DCM)小鼠心肌纤维化的影响。方法按照体重将小鼠随机分为5组:正常组、模型组和低、中、高3个剂量实验组,每组10只。除正常组外,小鼠给予高脂饲料喂养,同时腹腔内注射链脲佐菌素溶液100 mg·kg^(-1)建立DCM小鼠模型。16周后,3个剂量实验组予罗格列酮1,2和4 mg·kg^(-1)·d^(-1)灌胃,余2组予等体积生理盐水灌胃治疗,干预12周。计算小鼠心脏指数,以脱氧核糖核苷酸末端转移酶介导的缺口末端标记法检测细胞凋亡率,酶联免疫吸附法检测乳酸脱氢酶(LDH)水平,蛋白质印迹法检测金属蛋白酶组织抑制因子-2(TIMP2)蛋白表达水平(灰度值)。结果正常组、模型组和低、中、高3个剂量实验组的心脏指数分别为(3.69±1.01),(7.55±1.49),(6.33±1.26),(5.21±1.32)和(4.13±0.94)mg·kg^(-1);这5组的心肌细胞凋亡率分别为(3.72±0.94)%,(24.85±4.63)%,(18.48±3.17)%,(16.52±3.25)%和(10.54±2.66)%;这5组的LDH分别为(1.23±0.31),(2.48±0.56),(2.02±0.44),(1.85±0.37)和(1.52±0.38)U·L^(-1);这5组的TIMP2蛋白表达水平分别为0.09±0.02,0.67±0.31,0.49±0.22,0.33±0.15和0.14±0.05;与正常组相比,模型组上述指标差异均有统计学意义(均P<0.05);低、中、高3个剂量实验组的上述指标与模型组相比差异均有统计学意义(均P<0.05)。结论罗格列酮抑制DCM小鼠心肌纤维化进程,效果与剂量呈正相关。
Objective To investigate the effect of rosiglitazone on myocardial fibrosis in diabetic cardiomyopathy(DCM)mice.Methods Mice were randomly divided into 5 groups according to weight:normal group,model group,and experimental-L,experimental-M and experimental-H groups.DCM mice model was constructed with high-quality diet and Streptozotocin except normal group.After 16 weeks,experimental-L,experimental-M and experimental-H groups were given rogliede with 1,2 and 4 mg·kg^(-1)·d^(-1),while others were given equal volume of normal saline for 12 weeks.Heart weight index of mice were calculated.The cell apoptosis index were detected by Td T-mediated d UTP nick-end labeling.Levels of lactate dehydrogenase(LDH)in myocardial tissue was detected by enzyme-linked immunosorbent.Expression levels(gray value)of tissue inhibitor of metalloproteinase-2(TIMP2)protein was detected by using Western blot.Results The cardiac index in normal group,model,experimental-L,experimental-M and experimental-H group were(3.69±1.01),(7.55±1.49),(6.33±1.26),(5.21±1.32)and(4.13±0.94)mg·kg^(-1);the apoptosis index of cardiomyocytes in the five groups were(3.72±0.94),(24.85±4.63),(18.48±3.17),(16.52±3.25)and(10.54±2.66)%;level of LDH in the five groups were(1.23±0.31),(2.48±0.56),(2.02±0.44),(1.85±0.37)and(1.52±0.38)U·L^(-1);the expression level of TIMP2 protein in the five groups were 0.09±0.02,0.67±0.31,0.49±0.22,0.33±0.15 and0.14±0.05.Comparison between model group and normal group,the difference of the factors were significant(all P<0.05);comparison between three doses experimental groups and model group,the difference of the factors were significant(all P<0.05).Conclusion Rosiglitazone inhibited myocardial fibrosis in DCM mice,and effect had a relationship with dosage.
作者
管海燕
耿洲
杨文斌
GUAN Hai-yan;GENG Zhou;YANG Wen-bin(Department of Pharmacy,The Second Affiliated Hospital of Suzhou University,Suzhou 215151.Jiangsu Province,China)
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2021年第21期2917-2919,2928,共4页
The Chinese Journal of Clinical Pharmacology
基金
江苏省自然科学基金资助项目(BK20160231)。
关键词
罗格列酮
糖尿病心肌病
心肌纤维化
心脏指数
心肌细胞凋亡率
rosiglitazone
diabetic cardiomyopathy
myocardial fibrosis
cardiac index
apoptosis index of cardiomyocytes
