Abstract:
OBJECTIVE To investigate the mechanisms by which Pinggan Yishen Decoction (PGYSD) contributes to alleviating target organ damage in spontaneously hypertensive rats.
METHODS The chemical components of PGYSD were determined by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) and were analyzed by target analysis and functional enrichment combined with network pharmacology methods to predict the potential mechanism of PGYSD in treating hypertension and its target organ damage. Spontaneously hypertensive rats were randomly divided into the model group, low-dose PGYSD group (2 g ·kg-1), high-dose PGYSD group (5 g ·kg-1), and valsartan group (7.2 mg ·kg-1), with 6 rats in each group. Wistar-Kyoto rats were used as the control group, and the control group and the model group were gavaged with normal saline for 8 consecutive weeks. HE and Masson staining were used to observe the pathological damage and fibrosis degree of rat heart and thoracic aorta. Immunohistochemical staining and Western blot were used to detect the expression level of EGFR in the heart, liver and kidney of rats. Immunofluorescence staining was used to detect the co-localization of EGFR and EEA1 in the heart, liver and kidney of rats.
RESULTS Twenty-six components of PGYSD were detected by UPLC-Q-TOF/MS. Network pharmacology revealed that EGFR, PIK3R1 and EP300 may be key therapeutic targets of action of PGYSD for the treatment of hypertension and its target organ damage, and that the treatment of hypertension and its target organ damage by PGYSD may be closely related to EGFR tyrosine kinase inhibitor resistance, lipids and atherosclerosis and HIF-1 signaling pathway. The high-dose group of PGYSD significantly reduced systolic blood pressure and mean blood pressure in rats (P < 0.05, P < 0.01), attenuated pathological damage and fibrosis in the heart and thoracic aorta (P < 0.01, P < 0.001), significantly reduced the expression level of EGFR in the liver and kidney of rats (P < 0.01), and treated fibrosis in liver and kidney, reduced the co-localization of EGFR and EEA1 in the kidney of rats (P < 0.001), attenuated fibrosis in kidney.
CONCLUSION The paper integrates UPLC-Q-TOF/MS, network pharmacology and spontaneously hypertensive rat model and preliminarily explores the effect mechanism of PGYSD in the treatment of hypertension and its target organ damage, providing a scientific basis for further mechanism research and clinical application of PGYSD in the treatment of hypertension.
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