Study on the mechanism of Huoxue Lishui compound in treating spontaneous hypertensive rats based on TGF-β1-Smads signaling pathway

Abstract

Objective To explore the potential mechanism of Huoxue Lishui compound in treating spontaneous hypertension, and to provide basic theoretical and experimental basis for clarifying the efficacy of Huoxue Lishui compound in treating spontaneous hypertension based on TGF- β1- Smads signaling pathway. Methods Male spontaneously hypertensive rats aged 14 weeks were randomly divided into normal control group, model group, captopril group, low-dose group of Huoxue Lishui compound and high-dose group of Huoxue Lishui compound(n=20). The blood pressure of rats was monitored by tail artery noninvasive blood pressure meter. Hematoxylineosin (HE) staining was used to detect the ultrastructure of rat aorta. Immunohistochemical staining was used to detect the expression of transforming growth factor beta 1 (TGF-β1), connective tissue growth factor (CTGF), tissue inhibitor of metalloproteinase 1 (TIMP1), Ⅰ and Ⅲ collagen in aorta of each group. Immunoprecipitation was used to detect the expression of Smad2-Smad3 complex and Smad2-Smad3-Smad4 complex in each group. The expression of TGF- β1, Smad2, Smad3, Smad4, Smad7 and CTGF in serum of rats was detected by enzyme linked immunosorbent assay (ELISA). Results Compared with the normal control group, the blood pressure of model group was increased (P < 0.01). Compared with the model group, the blood pressure of captopril group was decreased from the 2nd week to the 4th week after treatment (P < 0.01), the blood pressure of low- dose group of Huoxue Lishui compound was decreased from the 3rd week to the 4th week after treatment (P < 0.05, P 0.05). Compared with the model group, the expression of TGF- β1, Smad2, Smad3, Smad4 and CTGF in the captopril group was significantly decreased (P < 0.05 or P < 0.01), while the expression of Smad7 was significantly increased (P < 0.05). The expression of TGF- β1, Smad2, Smad3, Smad4 and CTGF was decreased (P < 0.05 or P < 0.01), and Smad7 expression was increased (P < 0.05) in the the high-dose group of Huoxue Lishui compound. Conclusion Huoxue Lishui compound can effectively treat spontaneous hypertension through TGF-β1-Smads signaling pathway intervention, which provides theoretical basis for clinical treatment and related research of spontaneous hypertension in the later stage