Objective: To investigate the effect of SPH3127 on blood pressure regulation and its protective mechanism on cardiomyocytes in two-kidney one-clip (2K1C) hypertensive rats. Methods: A total of 100 male SD rats were divided into sham operation group, hypertension model group, SPH3127 group (10 mg/kg SPH3127), SPH3127+ZnPP group (10 mg/kg SPH3127+20 mg/kg ZnPP) and valsartan group (10 mg/kg). Systolic blood pressur (SBP) was measured by tail artery method. Left ventricular ejection fraction (LVEF), left ventricular short axis shortening rate (LVFS), left ventricular end-diastolic diameter (LVEDD) and left ventricular end-systolic diameter (LVESD) were evaluated by echocardiography. The morphological changes of myocardial cells were observed and the content of collagen fibers in myocardial tissue was detected. The contents of angiotensinⅡ(Ang Ⅱ) in serum, reactive oxygen species (ROS) and superoxide dismutase (SOD) in myocardial tissue were detected. The mRNA and protein expression levels of heme oxygenase-1 (HO-1) and peroxide-activating receptor γ-coactivator 1α (PGC-1α) in myocardial tissue were determined. Results: There was no significant difference in SBP between the groups before modeling (P＞0.05). After drug intervention, compared with the model group, the SBP of rats in each group was significantly decreased (P＜0.05), and the SBP of SPH3127 group and valsartan group was lower than that of SPH3127+ZnPP group (P＜0.05). After 4 weeks of drug intervention, the LVEF and LVFS values of the three groups of rats with drug intervention were higher than those of the model group (P＜0.05), while the LVEDD and LVESD values were lower (P＜0.05). Compared with the sham operation group, the degree of myocardial fibrosis in the model group was aggravated, the contents of AngⅡ and ROS were increased (P＜0.05), while the content of SOD was decreased (P＜0.05). Compared with the model group, the area of myocardial fibrosis in SPH3127 group, valsartan group and SPH3127+ZnPP group was decreased (P＜0.05), and the contents of Ang Ⅱand ROS were also decreased (P＜0.05). The mRNA and protein expression levels of HO-1 and PGC-1α in myocardial tissue of rats in the model group were lower than those in the sham operation group (P＜0.05), while the mRNA and protein expression levels of HO-1 and PGC-1α in the SPH3127 group were higher than those in the model group (P＜0.05). Compared with SPH3127 group, the expression levels of HO-1 and PGC-1α mRNA and protein in SPH3127+ZnPP group were decreased (P＜0.05). Conclusion: SPH3127 not only has a blood pressure-lowering effect, but also can exert myocardial protective effects by activating the HO-1/PGC-1α signaling pathway and inhibiting oxidative stress.
WANG Ruiqi
,
ZHANG Xin
,
YANG Shaohua
,
DONG Liang
. The protective effect of SPH3127 on hypertension and cardiomyocytes through HO-1/PGC-1α pathway[J]. Journal of Baotou Medical College, 2025
, 41(10)
: 41
-46
.
DOI: 10.16833/j.cnki.jbmc.2025.10.008
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