Effects of catalpol on necrotic apoptosis in rats with acute myocardial infarction by regulating the RIP1/RIP3/MLKL signaling pathway
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+8 μg·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-regulating the RIP1/RIP3/MLKL signaling pathway.
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