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Chinese Journal of Clinical Pharmacology and Therapeutics ›› 2020, Vol. 25 ›› Issue (11): 1214-1222.doi: 10.12092/j.issn.1009-2501.2020.11.002

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Inhibition of PI3K/AKT signaling pathway by sesamin and vitamin E improves left ventricular fibrosis in spontaneously hypertensive rats

ZHANG Junxiu 1, SHEN Yuanyuan 2, YANG Jieren 1, ZHENG Shuguo 1, HAO Wei 1   

  1. 1 Department of Pharmacology, Third-Grade Pharmacology Laboratory of State Administration of Traditional Chinese Medicine, Wannan Medical College, Wuhu 241002, Anhui, China; 2 Department of Clinical Pharmacy, Lu'an Second People's Hospital, Lu'an 237000, Anhui, China
  • Received:2020-07-07 Revised:2020-10-09 Online:2020-11-26 Published:2020-12-17
  • Contact: YANG Jieren, corresponding author, professor. E-mail: jryang1955@sina.com
  • About author:ZHANG Junxiu, MD, lecturer, mainly engaged in cardiovascular pharmacology research. E-mail: zhangjunxiu@wnmc.edu.cn
  • Supported by:
    Funded by National Natural Science Foundation of China (81600645); National Natural Science Foundation of China (81701161); The University Natural Science Research key Project of Anhui Province (KJ2015A192)

Abstract: AIM: Sesamin (Ses) is one of the major lignans in sesame seeds with antihypertensive and antifibroticactivities, but its effect is weak. In this experiment, we combined vitamin E (VitE) and Ses to observe their effects on blood pressure and left ventricular fibrosis in spontaneously hypertensive rats (SHRs), and to explore its possible mechanism.  METHODS: Male SHRs were randomly divided into SHRs+Ses+VitE group, SHRs+Ses group, SHRs+VitE group, and SHRs model group. Wistar-Kyoto (WKY) rats were setted as a normal control group. After 10 weeks of administration, systolic blood pressure (SBP) of rats was measured by tail cuff method, and the left ventricle was taken to calculate the organ index. Collagen deposition was observed by Masson staining, and cardiac collagen volume fraction (CVF) was analyzed. Expressions of collagen I, collagen III, transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF), matrix metalloproteinase-9 (MMP-9), matrix metalloproteinase inhibitor-1 (TIMP-1), phosphorylated protein kinase B (p-AKT), protein kinase B (AKT) and phosphoinositol 3 kinase (PI3K) were observed by Western blot. RESULTS: SBP, HW/BW, LVW/HW and CVF in SHRs+Ses+VitE group decreased significantly, and the decrease was higher than that in SHRs+Ses and SHRs+VitE group (P<0.01 or P<0.05). The expression of collagen I, collagen III, TGF-1, CTGF, MMP-9, TIMP-1, p-AKT and PI3K in SHRs+Ses+VitE group decreased significantly, and the decrease was higher than that in SHRs+Ses and SHRs+VitE group (P<0.01 or P<0.05). CONCLUSION: Ses combined with VitE can reduce the expression of TGF-1, CTGF, MMP-9 and TIMP-1 by inhibiting the activation of AKT/PI3K signaling pathway, thus exerting the effect of lowering blood pressure and improving left ventricular fibrosis.

Key words: sesamin, vitamin E, hypertension, fibrosis, TGF-β1, CTGF, PI3K/AKT

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