Mechanism of clopidogrel in salt-sensitive hypertensive rats
10.3969/j.issn.1671-7856.2025.07.008
- VernacularTitle:氯吡格雷在大鼠盐敏感性高血压的作用机制探讨
- Author:
Hongya MAO
1
;
Xiaoliang JIANG
;
Xing LIU
;
Zhiwei YANG
Author Information
1. 北京卫生职业学院,北京 102433
- Publication Type:Journal Article
- Keywords:
salt-sensitive hypertension;
clopidogrel;
platelet activation;
kidney inflammation;
p38MAPK/NF-κB signaling pathway
- From:
Chinese Journal of Comparative Medicine
2025;35(7):84-91
- CountryChina
- Language:Chinese
-
Abstract:
Objective To examine the role and mechanism of clopidogrel in the development of salt-sensitive hypertension.Methods 8-week-old Dahl salt-sensitive(Dahl SS)rats and control salt-resistant(SS13BN)rats were divided randomly into six groups and fed for 8 weeks with normal salt(0.4％NaCl,NS),high salt(8％NaCl,HS),or high salt combined with clopidogrel gavage(8％NaCl+10 mg/(kg·d))clopidogrel,HS+CLO).Arterial systolic blood pressure was measured continuously over 8 weeks by the tail-cuff method,and systolic blood pressure was measured by carotid cannulation after 8 weeks(56 days).Renal histopathology was observed by hematoxylin and eosin staining,and renal inflammatory cell infiltration was detected by immunohistochemistry.Peripheral blood platelet activation and platelet-leukocyte aggregation were analyzed by flow cytometry,and the renal inflammation-related proteins tumor necrosis factor-α,interleukin(IL)-1β,IL-6,and key proteins in the p38MAPK/nuclear factor(NF)-κB signaling pathway were detected by Western blot.Results Compared with the NS group,Dahl SS HS rats had significantly increased blood pressure(P＜0.05),aggravated renal tissue damage,increased inflammatory cell infiltration,increased expression of inflammatory cytokines(P＜0.05),elevated peripheral blood platelet activation(P＜0.05)and platelet-leukocyte aggregation(P＜0.05),and increased expression of p38MAPK/NF-κB signaling pathway proteins(P＜0.05).Clopidogrel effectively alleviated these phenotypes induced by high salt in Dahl SS rats.Conclusions Clopidogrel alleviated high-salt-induced salt-sensitive hypertension and decreased renal inflammatory responses and dysfunction in Dahl SS rats by inhibiting platelet activation and the p38MAPK/NF-κB signaling pathway.
