阿托伐他汀对急性心肌梗死大鼠心肌炎症及纤维化反应notch1信号通路
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LI Xiaolin1，LIU Yongxin2 Author Affiliations：1Characteristic Medical Center of the Chinese People’s Armed Police Force，Tianjin 300162，China；
2Cardiovascular Medicine，Hebei Provincial People’s Hospital，Shijiazhuang，Hebei 050051，China
The effect of atorvastatin on Notch1 signal pathway and the expression of TGF⁃β in myocardial inflammation
and fibrosis in rats with acute myocardial infarction
李晓琳 1，刘永欣 2 作者单位：1中国人民武装警察部队特色医学中心药剂科，天津 300162；
2河北省人民医院心血管内科，河北 石家庄 050051
基金项目：河北省2018年度医学科学研究重点课题计划（201800029）
摘要：目的 观察阿托伐他汀对急性心肌梗死（AMI）大鼠心肌炎症及纤维化反应 Notch1 信号通路、转化生长因子⁃β（TGF⁃β）的 影响。方法 选取 60 只健康雄性大鼠，按随机数字表法分为三组，各 20 只，对照组大鼠行前降支分离但未结扎，AMI 组行 AMI 建模，但不予以药物，治疗组行 AMI 建模后予以阿托伐他汀者，回顾性对比分析三组心肌炎性因子、纤维化反应情况。结果 AMI 组、治疗组大鼠肿瘤坏死因子⁃α（TNF⁃α）、白细胞介素⁃1β（IL⁃1β）水平高于对照组［（156.27±4.52）pg/mL、（131.26±5.23）pg/ mL 比（24.65±2.58）pg/mL；（97.65±12.33）pg/mL、（72.37±6.72）pg/mL 比（13.01±1.19）pg/mL，P＜0.05］，治疗组大鼠 TNF⁃α、IL⁃1β 低于 AMI 组［（131.26±5.23）pg/mL 比（156.27±4.52）pg/mL；（72.37±6.72）pg/mL 比（97.65±12.33）pg/mL］，差异有统计学意义（P＜ 0.05）；AMI 组、治疗组大鼠左室射血分数、左室短轴短缩率均低于对照组［（36.01±2.16）%、（55.82±3.25）%比（66.71±1.21）%； （18.21±2.33）%、（26.98±1.34）%比（37.83±0.84）%，P＜0.05］，而治疗组左室射血分数、左室短轴短缩率比 AMI 组高［（55.82± 3.25）%比（36.01±2.16）%；（26.98±1.34）%比（18.21±2.33）%］，差异有统计学意义（P＜0.05）；对照组大鼠心肌细胞排列整齐，心 肌组织分布正常，AMI 组大鼠心肌细胞减少、梗死区可见大量胶原纤维组织，治疗组改变介于对照组与 AMI 组之间；AMI 组、治 疗组 Notch1 蛋白、TGF⁃β 水平较对照组高，治疗组 Notch1 蛋白、TGF⁃β 水平低于 AMI 组，差异有统计学意义（P＜0.05）。结论 阿托伐他汀可通过抑制 Notch1 信号通路、TGF⁃β 改善 AMI 大鼠心肌炎症、纤维化反应。 关键词：心肌梗死； 受体，Notch； 转化生长因子 β； 白细胞介素 1β； 每搏输出量； 纤维化； 大鼠； 阿托伐他汀
安 徽 医 药 Anhui Medical and Pharmaceutical Journal 2020 Mar，24（3）
·429·
doi：10.3969/j.issn.1009⁃6469.2020.03.002
◇药学研究◇
阿托伐他汀对急性心肌梗死大鼠心肌炎症及纤维化反应 Notch1 信号通路、转化生长因子⁃β 的影响
Abstract：Objective To observe the effect of atorvastatin on Notch1 signal pathway and the expression of transforming growth fac⁃ tor⁃β（TGF⁃β）in myocardial inflammation and fibrosis in rats with acute myocardial infarction （AMI）. Methods Sixty healthy male rats were randomபைடு நூலகம்y selected and divided into three groups，with 20 cases in each group.The control group was separated by an⁃ terior descending branch but not ligated，the AMI models were established but no drug was given in the AMI group，the treatment
group was treated with Atorvastatin after the AMI was modeled.The inflammatory cytokines and fibrosis of the three groups were ret⁃ rospectively compared.Results The level of Tumor Necrosis Factor⁃α（TNF⁃α）and Interleukin⁃1β（IL⁃1β）in AMI Group and treatment group were higher than those in the control group［（156.27±4.52）pg/mL，（131.26±5.23）pg/mL vs（. 24.65±2.58）pg/mL； （97.65±12.33）pg/mL，（72.37±6.72）pg/mL vs（. 13.01±1.19）pg/mL，P＜0.05］，and the TNF⁃α and IL⁃1β in the treatment group were lower than those in the AMI Group［（131.26±5.23）pg/mL vs（. 156.27±4.52）pg/mL；（72.37±6.72）pg/mL vs（. 97.65±12.33）pg/ mL］.The differences were statistically significant（P＜0.05）.Left ventricular ejection fraction，left ventricular short axis shortening rate in AMI group and treatment group were lower than those in the control group［（36.01±2.16）%，（55.82±3.25）% vs（. 66.71± 1.21）%；（18.21±2.33）%，（26.98±1.34）% vs（. 37.83±0.84）%，P＜0.05］，while those in the treatment group were higher than those of AMI group［（55.82±3.25）% vs（. 36.01±2.16）%；（26.98±1.34）% vs（. 18.21±2.33）%］，the differences were statistically signifi⁃ cant（P＜0.05）.The myocardial cells in the control group were arranged neatly and the myocardium was distributed normally.The
2Cardiovascular Medicine，Hebei Provincial People’s Hospital，Shijiazhuang，Hebei 050051，China
The effect of atorvastatin on Notch1 signal pathway and the expression of TGF⁃β in myocardial inflammation
and fibrosis in rats with acute myocardial infarction
李晓琳 1，刘永欣 2 作者单位：1中国人民武装警察部队特色医学中心药剂科，天津 300162；
2河北省人民医院心血管内科，河北 石家庄 050051
基金项目：河北省2018年度医学科学研究重点课题计划（201800029）
摘要：目的 观察阿托伐他汀对急性心肌梗死（AMI）大鼠心肌炎症及纤维化反应 Notch1 信号通路、转化生长因子⁃β（TGF⁃β）的 影响。方法 选取 60 只健康雄性大鼠，按随机数字表法分为三组，各 20 只，对照组大鼠行前降支分离但未结扎，AMI 组行 AMI 建模，但不予以药物，治疗组行 AMI 建模后予以阿托伐他汀者，回顾性对比分析三组心肌炎性因子、纤维化反应情况。结果 AMI 组、治疗组大鼠肿瘤坏死因子⁃α（TNF⁃α）、白细胞介素⁃1β（IL⁃1β）水平高于对照组［（156.27±4.52）pg/mL、（131.26±5.23）pg/ mL 比（24.65±2.58）pg/mL；（97.65±12.33）pg/mL、（72.37±6.72）pg/mL 比（13.01±1.19）pg/mL，P＜0.05］，治疗组大鼠 TNF⁃α、IL⁃1β 低于 AMI 组［（131.26±5.23）pg/mL 比（156.27±4.52）pg/mL；（72.37±6.72）pg/mL 比（97.65±12.33）pg/mL］，差异有统计学意义（P＜ 0.05）；AMI 组、治疗组大鼠左室射血分数、左室短轴短缩率均低于对照组［（36.01±2.16）%、（55.82±3.25）%比（66.71±1.21）%； （18.21±2.33）%、（26.98±1.34）%比（37.83±0.84）%，P＜0.05］，而治疗组左室射血分数、左室短轴短缩率比 AMI 组高［（55.82± 3.25）%比（36.01±2.16）%；（26.98±1.34）%比（18.21±2.33）%］，差异有统计学意义（P＜0.05）；对照组大鼠心肌细胞排列整齐，心 肌组织分布正常，AMI 组大鼠心肌细胞减少、梗死区可见大量胶原纤维组织，治疗组改变介于对照组与 AMI 组之间；AMI 组、治 疗组 Notch1 蛋白、TGF⁃β 水平较对照组高，治疗组 Notch1 蛋白、TGF⁃β 水平低于 AMI 组，差异有统计学意义（P＜0.05）。结论 阿托伐他汀可通过抑制 Notch1 信号通路、TGF⁃β 改善 AMI 大鼠心肌炎症、纤维化反应。 关键词：心肌梗死； 受体，Notch； 转化生长因子 β； 白细胞介素 1β； 每搏输出量； 纤维化； 大鼠； 阿托伐他汀
安 徽 医 药 Anhui Medical and Pharmaceutical Journal 2020 Mar，24（3）
·429·
doi：10.3969/j.issn.1009⁃6469.2020.03.002
◇药学研究◇
阿托伐他汀对急性心肌梗死大鼠心肌炎症及纤维化反应 Notch1 信号通路、转化生长因子⁃β 的影响
Abstract：Objective To observe the effect of atorvastatin on Notch1 signal pathway and the expression of transforming growth fac⁃ tor⁃β（TGF⁃β）in myocardial inflammation and fibrosis in rats with acute myocardial infarction （AMI）. Methods Sixty healthy male rats were randomபைடு நூலகம்y selected and divided into three groups，with 20 cases in each group.The control group was separated by an⁃ terior descending branch but not ligated，the AMI models were established but no drug was given in the AMI group，the treatment
group was treated with Atorvastatin after the AMI was modeled.The inflammatory cytokines and fibrosis of the three groups were ret⁃ rospectively compared.Results The level of Tumor Necrosis Factor⁃α（TNF⁃α）and Interleukin⁃1β（IL⁃1β）in AMI Group and treatment group were higher than those in the control group［（156.27±4.52）pg/mL，（131.26±5.23）pg/mL vs（. 24.65±2.58）pg/mL； （97.65±12.33）pg/mL，（72.37±6.72）pg/mL vs（. 13.01±1.19）pg/mL，P＜0.05］，and the TNF⁃α and IL⁃1β in the treatment group were lower than those in the AMI Group［（131.26±5.23）pg/mL vs（. 156.27±4.52）pg/mL；（72.37±6.72）pg/mL vs（. 97.65±12.33）pg/ mL］.The differences were statistically significant（P＜0.05）.Left ventricular ejection fraction，left ventricular short axis shortening rate in AMI group and treatment group were lower than those in the control group［（36.01±2.16）%，（55.82±3.25）% vs（. 66.71± 1.21）%；（18.21±2.33）%，（26.98±1.34）% vs（. 37.83±0.84）%，P＜0.05］，while those in the treatment group were higher than those of AMI group［（55.82±3.25）% vs（. 36.01±2.16）%；（26.98±1.34）% vs（. 18.21±2.33）%］，the differences were statistically signifi⁃ cant（P＜0.05）.The myocardial cells in the control group were arranged neatly and the myocardium was distributed normally.The