梓醇调节RIP1/RIP3/MLKL信号通路对急性心肌梗死大鼠坏死性凋亡的影响  

Effects of catalpol on necrotic apoptosis in rats with acute myocardial infarction by regulating the RIP1/RIP3/MLKL signaling pathway

作　　者：李海莎 彭慧如 罗辉 谭文婷 李曾 LI Hai-sha;PENG Hui-ru;LUO Hui;TAN Wen-ting;LI Zeng(Cardiac Function Room,The First Hospital of Changsha,Changsha 410005,Hunan Province,China;Department of Cardiology,The First Hospital of Changsha,Changsha 410005,Hunan Province,China;Department of Infectious Disease,The First Hospital of Changsha,Changsha 410005,Hunan Province,China)

机构地区：[1]长沙市第一医院,心功能室,湖南长沙410005 [2]长沙市第一医院,心内科,湖南长沙410005 [3]长沙市第一医院,传染病科,湖南长沙410005

出　　处：《中国临床药理学杂志》2024年第14期2063-2067,共5页The Chinese Journal of Clinical Pharmacology

基　　金：长沙市科技计划基金资助项目(kq2208456)。

摘　　要：目的探究梓醇(CAT)对急性心肌梗死(AMI)大鼠坏死性凋亡的影响。方法用结扎左冠状动脉前降支的方法构建大鼠AMI模型。将60只SPF级SD雄性大鼠随机分为假手术组(Sham组)、AMI模型组(Model组)、低剂量CAT组(CAT-L组,30 mg·kg^(-1) CAT)、高剂量CAT组(CAT-H组,60 mg·kg^(-1) CAT)和高剂量CAT+RIP1激活剂重组RIP1组[CAT-H+rRIP1组,60 mg·kg^(-1) CAT+8μg·kg^(-1)重组大鼠受体相互作用蛋白激酶-1(rRIP1)],每组12只。CAT采取灌胃给药,每日1次,共给药4周。rRIP1采取尾静脉注射,隔天给药,共4周。Sham组、Model组分别灌胃和尾静脉注射等量的0.9%NaCl。CAT-L组、CAT-H组灌胃的同时需隔天尾静脉注射0.9%NaCl。TUNEL染色法观察大鼠心肌细胞凋亡情况。蛋白质印迹法检测大鼠心肌组织RIP1/RIP3/MLKL信号通路相关蛋白的表达。结果Sham组、Model组、CAT-H组和CAT-H+rRIP1组大鼠的心肌细胞凋亡率分别为(4.23±0.63)%、(33.48±3.94)%、(13.50±1.86)%和(29.62±3.08)%,心肌组织RIP1蛋白相对表达水平分别为0.21±0.02、0.86±0.09、0.43±0.04和0.72±0.07,RIP3蛋白相对表达水平分别为0.30±0.03、0.94±0.09、0.49±0.05和0.83±0.08,MLKL蛋白磷酸化水平分别为0.35±0.04、1.13±0.11、0.64±0.06和0.97±0.10。Model组上述指标与Sham组比较,CAT-H组的上述指标与Model组和CAT-H+rRIP1组比较,在统计学上差异均有统计学意义(均P<0.05)。结论CAT可能通过下调RIP1/RIP3/MLKL信号通路抑制AMI大鼠心肌细胞的坏死性凋亡。Objective To investigate the effect of catalpol(CAT)on necrotic apoptosis in acute myocardial infarction(AMI)rats.Methods Rat AMI model was constructed by ligating the anterior descending branch of the left coronary artery.Sixty SPF grade SD male rats were randomly grouped into sham surgery group(Sham group),AMI model group(Model group),low-dose CAT group(CAT-L group,30 mg·kg^(-1)CAT),high-dose CAT group(CAT-H group,60 mg·kg^(-1)CAT),and high-dose CAT+RIP1 activator recombinant RIP1 group(CAT-H+rRIP1 group,60 mg·kg^(-1)CAT+8μg·kg^(-1)rRIP1),12 in each group.CAT was administered by gavage once a day for a total of 4 weeks.Recombinant RIP1 was administered via tail vein injection and the next day for a total of 4 weeks.Sham group and Model group were given equal amounts of physiological saline by gavage and tail vein injection,respectively.The CAT-L group and CAT-H group were injected with physiological saline via the tail vein the next day while receiving gastric lavage.TUNEL staining was applied to observe the apoptosis of rat cardiomyocytes.Western Blot was applied to detect the expression of RIP1/RIP3/MLKL signaling pathway related proteins in rat myocardial tissue.Results The apoptosis rates of myocardial cells in the sham group,model group,CAT-L group,CAT-H group,and CAT-H+rRIP1 group were(4.23±0.63)%,(33.48±3.94)%,(13.50±1.86)%,and(29.62±3.08)%,respectively;the expression levels of RIP1 protein in myocardial tissue were 0.21±0.02,0.86±0.09,0.43±0.04,and 0.72±0.07,respectively;the expression levels of RIP3 protein were 0.30±0.03,0.94±0.09,0.49±0.05,and 0.83±0.08,respectively;the phosphorylation levels of MLKL protein were 0.35±0.04,1.13±0.11,0.64±0.06,and 0.97±0.10,respectively.The above indexes in Model group were compared with those in Sham group,and those in CAT-H group were compared with those in Model group and CAT-H+rRIP1 group,and the differences were statistically significant(all P<0.05).Conclusion CAT may inhibit necrotic apoptosis of myocardial cells in AMI rats by down-regulati

关 键 词：梓醇 受体相互作用蛋白激酶-1/受体相互作用蛋白激酶-3/混合谱系激酶结构域样蛋白信号通路 急性心肌梗死 坏死性凋亡 

分 类 号：R28[医药卫生—中药学]