Effect of Zhilong Huoxue Tongyu(蛭龙活血通瘀)Capsule on Hypertensive Myocardial Fibrosis by Regulating NLRP3 Signal Pathway
Objective:To study the effect and mechanism of the Zhilong Huoxue Tongyu(蛭龙活血通瘀胶囊)Capsule on mice with hypertensive myocardial fibrosis by regulating the NLRP3 signaling pathway.Methods:In this study,the mouse model of hypertensive myocardial fibrosis was established by continuous infusion of exogenous Ang Ⅱ of 1.46 mg/kg for 28 d through a subcutaneous osmotic sustained release pump.After modeling,the mice were randomly divided into a normal control group,a model control group,Zhilong Huoxue Tongyu Capsule(1.56 g/kg,3.12 g/kg,and 6.24 g/kg)groups,and fosinopril sodium(2.6×10-3 g/kg)group.Mice were given with corresponding drugs or normal saline,once a day for four weeks.At the same time,blood pressure was measured every week.The results of the model were evaluated accord-ing to whether the arterial systolic blood pressure level was above 150 mmHg and the results of Masson staining.After four weeks,left ventricu-lar ejection fraction(LVEF),left ventricular fraction shortening(LVFS),Left ventricular end-systolic dimension(LVESD),left ventricular end-diastolic dimension(LVEDD),and other cardiac function indexes were measured and analyzed.Enzyme-linked immunosorbent assay(ELISA)was used to detect serum levels of brain natriuretic peptide(BNP)and interleukin(IL)-1β.The changes in cardiomyocyte mor-phology and collagen fibers were observed by hematoxylin-eosin(HE)and Masson staining.Immunohistochemical staining was used to detect the positive expressions of fibronectin(FN)and NOD-like receptor thermal protein domain associated protein 3(NLRP3).Western blot and quantitative real-time polymerase chain reaction(qRT-PCR)were used to detect the protein and mRNA expressions of FN,α-smooth muscle actin(α-SMA),NLRP3,Cysteinyl aspartate specific proteinase-1(Caspase-1),IL-1β,and apoptosis-associated speck-like protein containing CARD(Asc).Results:After infusion of Ang Ⅱ,the systolic blood pressure of mice reached 150 mmHg.Masson results showed a large number of blue collagen fibers,indicating successful molding.Compared with the normal control group,the LVEF and LVFS indexes of the model con-trol group were decreased significantly,while the LVEDD and LVESD indexes were increased significantly(P＜0.01).Cardiomyocytes are hy-pertrophic and disordered,with a large number of blue collagen fibers.The content of BNP and IL-1β was increased significantly(P＜0 01).The mRNA and protein expressions of Fn,α-Sma,Nlrp3,Caspase-1,Il-1β,and Asc were significantly up-regulated(P＜0.01).Compared with the model control group,the LVEF and LVFS in each drug group were increased significantly(P＜0 01),while the LVEDD and LVESD inde-xes were decreased significantly(P＜0.05).The hypertrophy and disorder of cardiomyocytes were significantly improved.The area of blue col-lagen fibers in the myocardium was decreased significantly.The content of BNP and IL-1β was decreased(P＜0.01).The mRNA and protein expressions of Fn,α-Sma,Nlrp3,Caspase-1,IL-1β,and Asc were significantly down-regulated(P＜0.01).Conclusion:Zhilong HuoxueTongyu Capsule can improve the cardiac function injury of mice with hypertensive myocardial fiber,and its mechanism may be related to regulating the NLRP3 signal pathway,inhibiting the activation of NLRP3 inflammasomes,and then reducing the infiltration of inflammatory factors.
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