Empagliflozin Alleviates Sepsis-Induced Cardiac Inflammation Via the NF-κB Pathway

This study was aimed at analyzing the ameliorative effect of empagliflozin on cardiac inflammation in sepsis-induced rats and the underlying mechanism of action. Forty male SD rats were randomly divided into four groups of 10 rats each, control group (blank control), sepsis group (rat sepsis model prepared using the cecal ligation/puncture [CLP] method, low-dose group [CLP + 10 mg/kg/day empagliflozin gavage for 8 weeks], and high-dose group [CLP + 30 mg/kg/day empagliflozin gavage for 8 weeks]). The hemodynamic indexes of each group were monitored by physiological recorder, and inflammatory cell infiltration was detected by HE staining; the expression of inflammatory factor protein, apoptosis-related protein, and NF-κB pathway-related protein were detected by Western blot; CD45⁺ inflammatory cell infiltration in myocardial sections was detected by immunohistochemistry; the serum myocardial injury markers were determined by enzyme-linked immunosorbent assay. The number of CD45⁺ inflammatory cells infiltrated into myocardial sections was measured by immunohistochemistry, and the oxidative stress response in myocardial tissue was measured by enzyme-linked immunosorbent assay. Heart rate, mean arterial blood pressure (MABP), +LVdp/dt_max, and left ventricular systolic pressure (LVSP) were lower in the sepsis group than in the control group, and –LVdp/dt_max and left ventricular end-diastolic pressure (LVEDP) were higher than in the control group (P < 0.05); the heart rate, MABP, +LVdp/dt_max, and LVSP in the high-dose group > low-dose group > sepsis group; the –LVdp/dt_max, and LVEDP in the high-dose group < low-dose group < sepsis group (P < 0.05); the number of inflammatory cell infiltration scores, CD45⁺ inflammatory cell infiltration and IL-1 β, IL-6, TNF-α levels, and Caspase, Bax, P50, P65, IKBKG, EGR1, and TLR9 protein expression were higher in the sepsis group than in the control group, and Bcl-2 protein expression and Bcl-2 /Bax levels were lower than those in control group (P < 0.05); the expression of IL-10, Bcl-2 protein, and Bcl-2/Bax in the high-dose group > low-dose group > sepsis group; the inflammatory cell infiltration score and IL-1β, IL-6, TNF-α, Caspase, Bax, P50, P65, IKBKG, EGR1, and TLR9 protein expression in the high-dose group < low-dose group < sepsis group (P < 0.05); CK-MB, TnT, H-FABP, HMGB-1, ROS, MDA, and GSH-Px levels were higher and SOD levels were lower in the sepsis group than in the control group (P < 0.05), and CK-MB, TnT, H-FABP, HMGB-1, ROS, MDA, and GSH-Px levels in the high-dose group < low-dose group < sepsis group, and SOD levels in the high-dose group > low-dose group > sepsis group (P < 0.05). Empagliflozin can reduce sepsis-induced cardiac inflammation, myocardial injury, oxidative stress, and inflammatory cell infiltration, improve hemodynamics, and inhibit cardiomyocyte apoptosis; its mechanism of action may be related to the regulation of the NF-κB signaling pathway by empagliflozin.