Influences of Safflower Yellow on Cardiomyocyte Pyroptosis and Inflammatory Injury in Rats with Myocardial Infarction by Regulating NF-κB/NLRP3 Signaling Pathway
ZHAO Wen, ZHANG Yong, ZHANG Bo, et al
The 960th Hospital of the PLA, Shandong Ji'nan 250031, China
Abstract：Objective: To explore the influences of Carthamin yellow (CY) on the cardiomyocyte pyroptosis and inflammatory injury in myocardial infarction (MI) rats by regulating nuclear factor-κB (NF-κB)/NOD-like receptor protein 3 (NLRP3) signaling pathway. Methods: Rat MI model was established by ligation of left anterior descending coronary artery. The 72 SPF male rats were separated into: control group, sham group, model group, low-dose CY group (CY-L group, 20 mg/kg), high-dose CY group (CY-H group, 40 mg/kg), and high-dose CY+NF-κB activator group (CY-H+LPS group, CY 40 mg/kg+LPS 10mg/kg), 12 cases per group. After modeling, intraperitoneal injection was administered, once a day, for a total of 28 days. After the administration, the rats in each group were examined by echocardiography to detect the changes of cardiac function. 2,3,5-Triphenyltetrazolium chloride (TTC)-Evans blue (EB) method and immunofluorescence method were applied to detect myocardial infarction area and cardiomyocyte pyroptosis ratio in each group. Histopathological changes of myocardial tissue were observed by hematoxylin-eosin (HE) and Masson staining. The kits were used to measure the levels of interleukin (IL)-1β, IL-18 and lactate dehydrogenase (LDH) in rat myocardium. Western Blot was performed to detect the protein expression of NF-κB, NLRP3, cleaved-caspase1 and gastrin D-N (GSDMD-N) in myocardial tissue. Results: Compared with the sham group, the model group had severe myocardial tissue pathological damage and decreased cardiac function, the myocardial infarction area, the ratio of cardiomyocyte pyroptosis, the levels of IL-1β, IL-18, LDH, and the protein expression levels of NF-κB, NLRP3, GSDMD-N and cleaved-caspase1 in myocardial tissue were obviously increased (P<0.05). Compared with the model group, the cardiac function of the rats in the CY-L group and the CY-H group was obviously improved, the myocardial tissue damage was alleviated, and the cell pyroptosis was reduced, the levels of inflammatory factors IL-1β, IL-18 and LDH were obviously decreased, and the expression of NF-κB/NLRP3 signaling pathway-related proteins was obviously decreased (P<0.05). LPS attenuated the inhibitory effects of high-dose CY on cardiomyocyte pyroptosis and inflammatory injury in MI rats (P<0.05). Conclusion: CY may reduce the pyroptosis and inflammatory injury of cardiomyocytes in MI rats by inhibiting the NF-κB/NLRP3 signaling pathway.
2023, Vol. 29 
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