Xuebijing injection protects against sepsis-induced myocardial injury by regulating apoptosis and autophagy via mediation of PI3K/AKT/mTOR signaling pathway in rats

Abstract

Objective: Apoptosis and autophagy are significant factors of sepsis induced myocardial injury (SIMI). XBJ improves SIMI by PI3K/AKT/mTOR pathway. Present study is devised to explore the protective mechanism of XBJ in continuous treatment of SIMI caused by CLP. Methods: Rat survival was first recorded within 7 days. Rats were randomly assigned to three groups: Sham group, CLP group, and XBJ group. The animals in each group were divided into 12 h group, 1 d, 2 d, 3 d and 5 d according to the administration time of 12 hours, 1 day, 2 days, 3 days or 5 days, respectively. Echocardiography, myocardial injury markers and H&E staining were used to detect cardiac function and injury. IL-1β, IL-6 and TNF-α in serum were measured using ELISA kits. Cardiomyocyte apoptosis was assayed by TUNEL staining. Apoptosis and autophagy related proteins regulated by the PI3K/AKT/mTOR signaling pathway were tested using western blot. Results: XBJ increased the survival rate in CLP-induced septic Rat. First of all, the results of echocardiography, H&E staining and myocardial injury markers (cTnI, CK, and LDH levels) showed that XBJ could effectively improve the myocardial injury caused by CLP with the increase of treatment time. Moreover, XBJ significantly decreased the levels of serum inflammatory cytokines IL-1β, IL-6 and TNF-α in SIMI rats. Meanwhile, XBJ downregulated the expression of apoptosis-related proteins Bax, Cleaved-Caspase 3, Cleaved-Caspase 9, Cytochrome C and Cleaved-PARP, while upregulated the protein levels of Bcl-2 in SIMI rats. And, XBJ upregulated the expression of autophagy related protein Beclin-1 and LC3-II/LC3-I ratio in SIMI rats, whereas downregulated the expression of P62. Finally, XBJ administration downregulated the phosphorylation levels of proteins PI3K, AKT and mTOR in SIMI rats. Conclusions: Our results showed that XBJ has a good protective effect on SIMI after continuous treatment, and it was speculated that it might be through inhibiting apoptosis and promoting autophagy via, at least partially, activating PI3K/AKT/mTOR pathway in the early stage of sepsis, as well as promoting apoptosis and inhibiting autophagy via suppressing PI3K/AKT/mTOR pathway in the late stage of sepsis.

High-dose Vitamin C injection ameliorates against sepsis induced myocardial injury by anti-apoptosis, anti-inflammatory and pro-autophagy through regulating MAPK, NF-κB and PI3K/AKT/mTOR signaling pathways in rats

“…Inflammation and apoptosis are recognized as key pathophysiological phenomena in sepsis and SIMI at the cellular and molecular levels [7]. Many basic studies have indicated that regulate inflammation and apoptosis can reduce infectious cardiac insufficiency [35,36].…”

“…However, the mechanism by which sepsis-induced myocardial injury (SIMI) remains unclear [5,6]. Our previous studies have also demonstrated that autophagy and apoptosis play key roles in the occurrence and development of SIMI [7]. The PI3K/AKT/mTOR [8], MAPK [9] and NF-κB [10] and pathways regulate various biological responses, including proliferation, autophagy, inflammation, and apoptosis [11][12][13][14][15].…”

“Three medicines and three formulas” in COVID-19: From bench to bedside

“…XBJ ameliorates H2S-induced ARDS by promoting claudin-5 expression via the PI3K/AKT/Forkhead box protein O1 (FOXO1) signaling pathway [104] . XBJ produced a strong protective effect on sepsis-induced myocardial injury (SIMI) and may act by inhibiting apoptosis and promoting autophagy via , at least partially, activating PI3K/AKT/mTOR pathway in the early stage of sepsis, as well as promoting apoptosis and inhibiting autophagy via suppressing PI3K/AKT/mTOR pathway in the late stage of sepsis [105] . One of the main bioactive compounds is XBJ-benzoylpaeoniflorin (BPF).…”

Novel insights into the regulatory role of N6-methyladenosine methylation modified autophagy in sepsis

“…In the pathogenesis of sepsis, for instance, it has become clear that suppressing autophagy mechanisms by targeting SIRT4, MAPKs, and Nrf2 pathways may be a useful strategy for protecting organ function [177][178][179]. Indeed, it has also been demonstrated that autophagy is activated early in the onset of sepsis, but that as the condition progresses, autophagic activity declines [180,181]. There are opposing views in the existing literature on the crucial protective or destructive functions of autophagy in sepsis-induced organ damage.…”