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[摘要]
目的 探究刺甘草查尔酮对自噬、NLRP3炎症小体和脓毒症大鼠心肌损伤的影响。方法 将大鼠按照随机数表法分为Col、LPS、Ech L、Ech M、Ech H、阳性对照组。检测大鼠心功能指标(LVEDD、LVESD、FS、EF);ELISA检测血清中炎症因子(TNF-α、IL-1β)水平和心肌损伤标志物(cTnΙ、CK-MB)含量;HE染色检测心肌组织病理学变化;TUNEL检测心肌细胞凋亡率;蛋白质印迹检测心肌组织中自噬相关蛋白及炎性小体相关蛋白表达。结果 和Col组相比,LPS组大鼠心功能指标LVEDD、LVESD和血清中TNF-α、IL-1β、cTnΙ、CK-MB水平明显升高,FS、EF明显降低,心肌组织中p62、NLRP3、ASC、cleaved caspase-1蛋白表达和心肌细胞凋亡率均明显升高,组间差异有统计学意义(P<0.05);和LPS组相比,Ech L、Ech M与Ech H组心功能指标LVEDD、LVESD和血清中TNF-α、IL-1β、cTnΙ、CK-MB水平明显降低,FS、EF明显升高,心肌组织中LC3Ⅱ/LC3 Ι比值、Becline-1、p62均逐渐升高,NLRP3、ASC、cleaved caspase-1蛋白表达和心肌细胞凋亡率均逐渐降低,组间差异有统计学意义(P<0.05),且呈剂量依赖。结论 刺甘草查尔酮可减轻脓毒症大鼠心肌损伤,其可能和促进心肌组织中自噬和抑制NLRP3炎症小体激活有关。
[Key word]
[Abstract]
Objective To investigate the effects of licorice chalcone on autophagy, NLRP3 inflammasome and myocardial injury in sepsis rats. Methods The rats were randomly divided into Col group, LPS group, Ech L group, Ech M group, Ech H group and positive control group, 5 in each group. Cardiac function indexes (LVEDD, LVESD, FS, EF) were detected in rats; serum levels of inflammatory factors (TNF-α, IL-1β) and myocardial injury markers (cTn1, CK-MB) were detected by ELISA; myocardial injury was detected by HE staining Histopathological changes; TUNEL detection of cardiomyocyte apoptosis rate; Western blot detection of autophagy-related proteins and inflammasome-related proteins expression in myocardial tissue. Results Compared with the Col group, the LPS group showed the cardiac function indicators LVEDD, LVESD, in the serum of rats with TNF-α, IL-1β, cTnΙ, and the level of CK-MB were significantly increased, FS and EF were significantly reduced, and the expression of p62, NLRP3, ASC, cleaved caspase-1 protein in myocardial tissue and the apoptosis rate of myocardial cells were significantly increased, with significant differences between groups (P<0.05); Compared with the LPS group, the cardiac function indicators LVEDD, LVESD, and serum in the Ech L, Ech M, and Ech H groups were compared. TNF-α, IL-1β, cTnΙ, CK-MB levels significantly decreased, FS and EF significantly increased, and LC3Ⅱ/LC3 Ι in myocardial tissue, the expression of NLRP3, ASC, cleaved caspase-1 protein and the apoptosis rate of myocardial cells were gradually reduced, and the difference between groups was statistically significant (P<0.05), and was dose-dependent. Conclusion Licorice chalcone can alleviate myocardial injury in septic rats, which may be related to the promotion of autophagy in myocardial tissue and the inhibition of NLRP3 inflammasome activation.
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[基金项目]
山东省自然科学基金(ZR2021MH039),济南市科技局科技科技创新计划(202019089)