Abstract
The aim of this study was to assess the underlying impact of Tetramethylpyrazine (TMP), which is the main activity compound of Ligusticum chuanxiong Hort, on the blood–brain barrier, inflammatory and nitrous oxide systems in a rat model of lipopolysaccharide (LPS)-induced sepsis. The SD rats were divided into control group, LPS treatment group, and LPS + TMP treatment group. TMP administered by tail vein injection. The mortality of experimental rats was recorded during the experiment. Rats were sacrificed after 14 days. Peripheral blood was collected and the expression levels of inflammatory factors TNF-α, IL-1β, and IL-6 were detected by ELISA. The integrity of blood-brain barrier was detected by sodium fluorescein staining. Lung and brain tissues were taken to detect the infiltration of immune cells. Immunohistochemistry was performed to detect the expression of tight junctions related proteins and oxidative stress-related proteins. The results showed that TMP treatment for 14 days significantly decreased the weight loss and increased the survival rate of the septic rats significantly. TMP decreased the infiltration of inflammatory cells and alleviated the sepsis-induced damage in both the lung and brain tissues. The inflammatory cytokines TNF-α, IL-1β, and IL-6, were significantly decreased post-TMP treatment. Histopathological analysis with sodium fluorescein staining density showed that TMP had a protective effect on the basal lamina and cerebral cortex. Also, TMP significantly increased expression of the tight junction-related proteins claudin-5 and occludin in the brain tissue and increased the expression of the ZO-1, Occludin, and Claudin-5 genes, indicating alleviated the degree of blood–brain barrier destruction. Furthermore, immunohistochemistry (IHC) and immunoblotting confirmed that TMP could inhibit the indicators of the nitrous oxide system, iNOS and eNOS; in addition, TMP significantly decreased the levels of MDA and NO. The findings showed that TMP treatment during sepsis was associated with the protection of the blood–brain barrier and the suppression of inflammatory reactions and the nitrous oxide system. This study reveals a promising protective role of TMP in septic encephalopathy and may suggest a therapeutic approach for fighting the deadly disease of sepsis in the clinic.
Highlights
Sepsis, a systemic inflammatory response syndrome (SIRS), is caused by infection due to the presence of bacteria (Sursal et al, 2013)
The present study aimed to investigate the effects of TMP on LPS-induced sepsis in the sepsis rat model and to explore the underlying mechanism related to the blood–brain barrier, inflammation, and nitrous oxide systems
Based on calculations of the survival rate of the rats, the mortality of the LPS group significantly increased within 14 days (P0.01), reaching 50%, while the rats injected with TMP did not die within 14 days, which may indicate that TMP can rescue LPS-induced sepsis in rats to some extent and that TMP has an evident protective effect on sepsis
Summary
A systemic inflammatory response syndrome (SIRS), is caused by infection due to the presence of bacteria (Sursal et al, 2013). Sepsis is mainly associated with bacterial lipopolysaccharides (LPS) and is called endotoxemia (Lykkesfeldt et al, 2014; Xu et al, 2018). As a severe problem in the field of critical illness, sepsis is increasingly attracting the attention of clinicians and researchers. According to a large amount of clinical and experimental research, the data on sepsis treatment and new drug development did not seem to be promising (Fuchs et al, 2019; Zhang et al, 2019). Bacterial infection or bacterial LPS can be used to induce sepsis animal models (Sterns et al, 2005; Xu et al, 2018). LPS injection was shown to be an ideal and consistent protocol for establishing a sepsis model
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