Qingda granules mitigate cardiac inflammation in spontaneously hypertensive rats via the MCP-1/CCR2 signaling pathway

Abstract

Objective: This study investigated effects and underlying mechanisms of Qingda granules (QDG) on cardiac inflammation in spontaneously hypertensive rats (SHRs). Methods: Twelve SHRs (17 weeks old) were randomly divided into SHR and SHR + QDG groups, with six rats in each group. We also used six 17-week-old Wistar Kyoto (WKY) rats as the WKY group. While rats in the SHR + QDG group were administered QDG (0.8 g/kg/d) for eight weeks, those in the WKY and SHR groups were administered an equal volume of normal saline. Blood pressure was then monitored weekly. Subsequently, hematoxylin and eosin (HE) staining was used to detect pathological changes in the cardiac tissue. Besides, enzyme-linked immunosorbent assay (ELISA) was used to detect the serum content of inflammatory cytokines. Subsequently, real-time quantitative polymerase chain reaction and immunohistochemical (IHC) staining were conducted to determine the expression of inflammatory cytokines and inflammatory cell infiltration, including the activation of the MCP-1/CCR2 signaling pathway. Results: As observed, QDG inhibited the elevation of systolic blood pressure, diastolic blood pressure, and mean arterial pressure in the understudied SHRs. HE staining showed that this drug attenuated pathological changes and inflammatory cell infiltration of cardiac tissue samples in the SHRs. However, ELISA and IHC confirmed a reduction in the expression of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the serum and cardiac tissue of SHRs with QDG treatment. Additionally, QDG treatment significantly attenuated protein levels of interferon-γ, CD3, and Mac-2 in the cardiac tissue samples of SHRs. Moreover, mRNA and protein expressions of monocyte chemoattractant protein 1 (MCP-1) and chemotactic cytokine receptor 2 (CCR2), which were upregulated in cardiac tissue samples of SHRs, became downregulated through treatment with QDG. Conclusion: Therefore, by decreasing the levels of inflammatory cytokines and inflammatory cell infiltration through suppression of the MCP-1/CCR2 signaling pathway, QDG treatment attenuated blood pressure and cardiac inflammatory changes in SHRs.

Keywords

• Qingda granules
• Hypertension
• Cardiac inflammation
• MCP-1/CCR2 pathway