Objective: To elevate the effects of Qingxuan Jiangya Decoction (, QXJYD) on hypertension and vascular structural remodeling (VSR) in spontaneously hypertensive rats (SHRs), and investigate the underlying mechanisms.
Methods: SHRs (n=8) were given intra-gastric administration with 60 mg/kg of QXJYD or saline, daily for 8 weeks, while rats in SHR-control (n=8) and WKY (n=8) groups were received equal volumes of saline solution. Systolic blood pressures (SBP), diastolic blood pressures (DBP) and mean blood pressures (MBP) were measured once a week. The levels of angiotensin II (Ang II), endothelin 1 (ET-1) and plasma renin activity (PRA) were tested by enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay, respectively. The effect of QXJYD on VSR was determined by examining the media thickness and the ex vivo contractility of thoracic aortic. The proliferation and fibrosis of vascular smooth muscle cells (VSMCs) were examined via immunohistochemical (IHC) staining for proliferating cell nuclear antigen (PCNA), collagen I and collagen III, respectively. The mRNA and protein expressions of transforming growth factor β 1 (TGF-β 1), Smad3 and phosphorylation of Smad3 in thoracic aorta tissues were determined by real-time polymerase chain reaction (PCR) and Western blot assay, respectively.
Results: QXJYD treatment led to a significant decrease of the elevation of blood pressure in SHRs and reduced the levels of Ang II, ET-1 and PRA in the serum (P<0.05). In addition, QXJYD treatment remarkably ameliorated VSR and vascular function in SHRs. Moreover, QXJYD inhibited VSMC proliferation and fibrosis by suppressing the expression of PCNA, collagen I and collagen III in thoracic aortic. Furthermore, QXJYD inhibited the expression of TGF-β 1, Smad3 and the phosphorylation of Smad3, respectively (P<0.05).
Conclusion: QXJYD reversed VSR by inhibiting VSMC proliferation and collagen deposition via regulation of TGF-β 1/Smad signaling pathway, which may, in part, illuminate its anti-hypertensive activities.
Keywords: Chinese medicine; Qingxuan Jiangya Decoction; transforming growth factor-beta 1/Smad signaling pathway; vascular structural remodeling.