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06 December 2019 : Animal Research  

Resveratrol Protects the Myocardium in Sepsis by Activating the Phosphatidylinositol 3-Kinases (PI3K)/AKT/Mammalian Target of Rapamycin (mTOR) Pathway and Inhibiting the Nuclear Factor-κB (NF-κB) Signaling Pathway

Xiuling Shang1A, Kaiyang Lin2B, Rongguo Yu1G*, Pengli Zhu3DG, Yingrui Zhang1B, Ling Wang4C, Jingqing Xu1E, Kaihua Chen1F

DOI: 10.12659/MSM.918369

Med Sci Monit 2019; 25:9290-9298

Abstract

BACKGROUND: Sepsis combined with myocardial injury is an important cause of septic shock and multiple organ failure. However, the molecular mechanism of sepsis-induced myocardial dysfunction has not yet been thoroughly studied. Resveratrol has been an important research topic due its organ-protection function, but the specific mechanism is unclear. The purpose of this study was to explore the mechanism of organ injury in sepsis and to investigate the molecular mechanism of resveratrol in myocardial protection in sepsis.

MATERIAL AND METHODS: A classical Sprague-Dawley rat model of sepsis peritonitis was constructed for further experiments. The PI3K inhibitor LY294002 and resveratrol were used to intervene in a rat model of cardiomyopathy. HE staining was used to observe pathological changes. Cardiomyocyte apoptosis was detected by TUNEL assay. Western blot analysis was used to detect the level of maker proteins.

RESULTS: The PI3K inhibitors could promote cardiac abnormalities and apoptosis, but resveratrol showed the opposite effect. The upregulation function of the PI3K inhibitor on the expression of NF-κB, IL-6, IL-1β, and TLR4 in LPS rats was not obvious, but the expression of TNF-a in LPS+LY294002 rats was increased by 22.85% compared with that in LPS rats (P<0.05). Compared with the LPS group, the expression of NF-κB, TNF-α, IL-6, IL-1β, and TLR4 in the LPS+resveratrol group was decreased. The expression of p-PI3K, p-AKT, and p-mTOR in LPS+LY294002 was reduced. The expression p-PI3K, p-AKT, and p-mTOR in the myocardium of the LPS+resveratrol group was increased.

CONCLUSIONS: Resveratrol can protect the myocardium in sepsis by activating the PI3K/AKT/mTOR signaling pathway and inhibiting the NF-κB signaling pathway and related inflammatory factors.

Keywords: Class III Phosphatidylinositol 3-Kinases, myocardial injury, Receptor Activator of Nuclear Factor-kappa B, Sepsis, Cardiomyopathies, Chromones, Heart, Morpholines, Myocardium, Phosphatidylinositol 3-Kinases, Proto-Oncogene Proteins c-akt, resveratrol, TOR Serine-Threonine Kinases

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750