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Sepsis has the characteristics of high morbidity and high mortality, which is the main cause of death in critically ill patients. Peripheral 5-hydroxytryptamine (5-HT) is mainly synthesized and secreted by enterochromaffin cells and plays a role in the development and progression of inflammation. This article focuses on 5-HT, 5-HT transporter (SERT) and selective serotonin reuptake inhibitors (SSRIs) in immune response, inflammatory factor release, oxidative stress, intestinal bacterial translocation and microcirculation of sepsis. The role of the review is to find new ideas for the clinical treatment of sepsis.
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Background:Cerebellar fastigial nucleus (FN)is involved in regulation of visceral activities such as cardiovascular, ingestion,respiratory,and acute gastric mucosal injury,yet it is unclear whether it participates in the regulation of visceral hypersensitivity and what is the possible mechanism. Aims:To investigate the effect and possible mechanism of glutamic acid (Glu ) injection into cerebellar FN on chronic visceral hypersensitivity in rats. Methods: Chronic visceral hypersensitivity rat model was established by neonatal colorectal distension (CRD). After 8 weeks,the rats were divided into CRD group,solvent group (0. 2 μL 0. 9% NaCl solution injection into cerebellar FN),high-,medium-,low-dose Glu groups (12,6,3 μg Glu injection into cerebellar FN,respectively),3-MPA +Glu group (12 μg Glu injection after glutamate decarboxylase inhibitor 3-MPA injection into cerebellar FN),Bic + Glu group (12 μg Glu injection into cerebellar FN after GABAAreceptor blocker Bic injection into lateral hypothalamic area). Pain threshold,abdominal withdrawal reflex (AWR)score and abdominal external oblique muscle electromyography (EMG)were used to detect visceral sensitivity,and malondialdehyde (MDA)content and superoxide dismutase (SOD)activity were measured. Results:Chronic visceral hypersensitivity rat model was successfully established. Compared with CRD group,pain threshold was significantly increased (P＜0. 05),AWR score,EMG amplitude,MDA content were significantly decreased (P＜0. 05 ),and SOD activity was significantly increased in a dose-dependent manner in Glu group (P ＜0. 05 ). Compared with 12 μg Glu group,pain threshold was significantly decreased (P＜0. 05),AWR score,EMG amplitude, MDA content were significantly increased (P ＜0. 05),and SOD activity was significantly decreased in 3-MPA +Glu group,Bic+Glu group (P＜0. 05). Conclusions:Glu injection into cerebellar FN can significantly reduce the visceral sensitivity in rats. The mechanism may be that Glu in cerebellar FN produces GABA via glutamate decarboxylase,and then binding GABAAreceptor in lateral hypothalamic area,resulting in increased intestinal mucosal antioxidant capacity, thereby reducing visceral hypersensitivity.
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Objective To explore the protective effects of short-acting β31 receptor blocker esmolol on lung injury in septic rats and explore its mechanism.Methods Fifty-four male SpragueDawley rats were randomly(random number) divided into three groups (n=18 in each),namely sham operation group(Sham),sepsis group(Spesis),esmolol group(ES).Each group were further divided into three subgroups of 6 h,12 h and 24 h(n=6 in each subgroup).The sepsis models were established with cecal ligation and puncture (CLP) in rats of Sepsis group and ES group,while rats of SH group were treated with laparotomy without CLP.Dwelled cannulation in the left internal jugular vein was performed after the model establishment.Saline in the rate of 1 mL/h was continuously pumped intravenously into the rats of SH group and Sepsis group by micro pump for 6 h,and esmolol solution in the rate of 1 mL/h [15 mg/(kg·h)]was continuously pumped into the rats of ES group for 6h.Rats in each subgroup were sacrificed at 6h,12h and 24 h after modeling,separately.The levels of catecholamine (CA) in plasma and levels of NF-κB in lung tissue were measured by ELISA.The protein levels of TLR4 and NF-κB in lung tissue were detected by Western Blot.The protein content of alveolar lavage fluid,wet/dry weight ratio(W/D) of lung tissue,lung coefficient and lung water content were measured.The pathological changes of lung tissues were observed under an optical microscope.Results (①) The levels of CA in plasma in Sepsis and ES groups at 6 h after modeling was significantly increased compared with Sham group (P＜0.05),and the level of CA in plasma increased significantly in ES group compared with Sham and Sepsis groups (P＜0.05).At 12 h after modeling,level of CA in plasma was still significantly increased in ES group compared with SH group (P＜0.05);At 24 h after modeling,level of CA in plasma was increased significantly in ES group compared with Sepsis group (P＜0.05).(②) At 6 h,12 h and 24 h after modeling,levels ofNF-κ B in lung tissue were significantly increased in Sepsis group and ES group compared with SH group (P＜0.05),and levels of NFκ B in lung tissue in ES group were also significantly lower than those in Sepsis group at given intervals (P＜0.05).③ At 6 h,12 h and 24 h after modeling,protein content of alveolar lavage fluid,wet/dry weight ratio (W/D) in lung tissue,lung coefficient and lung water content in Sepsis group and ES group were significantly increased compared with SH group (P＜0.05),and protein content of alveolar lavage fluid,wet/ dry weight ratio (W/D) in lung tissue,lung coefficient and lung water content in ES group also significantly lower than those in Sepsis group at given intervals (P＜0.05).④ Western Blot revealed at 6 h,12 h and 24 h after modeling,the protein levels of TLR4 and NF-κ B in lung tissue in Sepsis group and ES group were significantly increased compared with SH group (P＜0.05),and the protein levels of TLR4 and NF-κ B in lung tissue of ES group were also significantly lower than those in Sepsis group at all given intervals (P＜0.05).⑤ The lightest degree of pathological change was observed in SH group,the most serious degree of pathological change was found in Sepsis group,and the pathological change was significantly alleviated in ES group compared with Sepsis group whereas the pathological change was significantly increased compared with SH group at all given intervals.Conclusions Esmolol can promote the secretion of catecholamine,inhibit the release of inflammatory cytokines,reduce lung permeability,reduce pulmonary edema,and thus play an important role in protecting the lungs.The mechanism may be that esmolol improves the responsiveness of β-adrenergic receptor to catecholamine,and regulates the level of inflammatory cytokines by inhibiting TLR4-NF-κB-TNF-α signaling pathways,thus exerting protective effect on the lungs.