摘要
目的探讨曲尼司特(TNL)对异丙肾上腺素(ISO)诱导的大鼠心肌肥厚和纤维化的影响。方法用连续7 d皮下注射5 mg·kg^(-1)·d^(-1)ISO的方法构建心肌肥厚大鼠模型。将45只参与造模的大鼠随机分为模型组、实验组和对照组,每组15只;另取15只正常大鼠设为空白组。造模开始后第2天,实验组灌胃给予50 mg·kg^(-1)·d^(-1)TNL溶液;对照组灌胃给予20 mg·kg^(-1)·d^(-1)卡托普利溶液;空白组和模型组均灌胃给予等量0.9%NaCl。4组大鼠均持续给药14 d。用称量法测定大鼠心脏质量指数,用蛋白质印迹法检测大鼠心肌组织中p38有丝分裂原活化蛋白激酶(p38MAPK)、p65和核因子-κB(NF-κB)蛋白的表达水平及其磷酸化水平。结果实验组、对照组、模型组和空白组的心脏质量指数分别为(3.00±0.09)、(2.92±0.11)、(3.42±0.10)和(2.60±0.06)mg·g^(-1),左心室质量指数分别为(2.34±0.06)、(2.29±0.07)、(2.60±0.08)和(2.00±0.05)mg·g^(-1),磷酸化p38MAPK(p-p38MAPK)/p38MAPK分别为0.36±0.03、0.19±0.02、0.47±0.04和0.14±0.01,p-p65/p65分别为0.30±0.02、0.18±0.02、0.52±0.03和0.10±0.01,p-NF-κB/NF-κB分别为0.40±0.02、0.24±0.01、0.73±0.04和0.11±0.01。实验组和对照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TNL能够减轻ISO诱导的大鼠心肌肥厚和纤维化,其作用机制可能与调控p38MAPK和NF-κB信号通路活性有关。
Objective To investigate the effect of tranilast(TNL)on myocardial hypertrophy and fibrosis induced by isoproterenol(ISO)in rats.Methods The rat model of myocardial hypertrophy was established by subcutaneous injection of ISO(5 mg·kg^(-1)·d^(-1))for 7 consecutive days.Forty five rats participating in modelling were randomly divided into model,experimental and control groups with 15 rats per group;another 15 normal rats were selected as bank group.On the second day after the establishment of the model,the rats in experimental group were given 50 mg·kg^(-1)·d^(-1) TNL solution by gavage,the rats in control group were given 20 mg·kg^(-1)·d^(-1) captopril solution by gavage,and the rats in bank and model groups were given the same amount of normal saline by gavage.Four groups were administered continuously for 14 days.The weight index of rat heart was measured by weighing method;The protein expression and phosphorylation levels of p38 mitogen activated protein kinase ( p38MAPK) ,p65 and nuclear factor - κB ( NF - κB) were measured by Western blot.Results The levels of Cardiac mass indexes in experimental,control,model and bank groups were ( 3. 00 ± 0. 09) ,( 2. 92 ± 0. 11 ) ,( 3. 42 ± 0. 10 ) and ( 2. 60 ± 0. 06 ) mg·g^(-1);the levels of left ventricular mass indexes were( 2. 34 ± 0. 06) ,( 2. 29 ± 0. 07) ,( 2. 60 ± 0. 08) and ( 2. 00 ± 0. 05) mg·g^(-1);the ratios of phosphorylated p38MAPK( p - p38MAPK) /p38MAPK were 0. 36 ± 0. 03,0. 19 ± 0. 02,0. 47 ± 0. 04 and 0. 14 ± 0. 01;the ratios of p - p65 /p65 were 0. 30 ± 0. 02,0. 18 ± 0. 02,0. 52 ± 0. 03 and 0. 10 ± 0. 01;the ratios of p - NF - κB /NF - κB were0. 40 ± 0. 02,0. 24 ± 0. 01,0. 73 ± 0. 04 and 0. 11 ± 0. 01. The above indexes of model group were significantlydifferent from those in experimental and control groups ( all P < 0. 05) . Conclusion TNL can reduce ISO inducedmyocardial hypertrophy and fibrosis in rats,and its mechanism may be related to the regulation of p38MAPK andNF - κB signaling pathway activity.
作者
张诗吟
李国栋
孙启银
张田杰
薛涛
ZHANG Shi-yin;LI Guo-dong;SUN Qi-yin;ZHANG Tian-jie;XUE Tao(Department of Cardiovascular Medicine,The First People’s Hospital of Huzhou,Huzhou 313000,Zhejiang Province,China;Department of Cardiovascular Medicine,Tongde Hospital of Zhejiang Province,Hangzhou 310012,Zhejiang Province,China)
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2023年第7期966-970,共5页
The Chinese Journal of Clinical Pharmacology
基金
浙江省中医药重点研究基金资助项目(2022ZB083)。
