ABSTRACT
Sepsis is a life-threatening organ dysfunction caused by an uncontrolled host response to infection. The mechanism of sepsis is extremely complicated and the mortality is still high. Persistent researches provide an important way to break through the "bottleneck" of clinical diagnosis and treatment of sepsis. In recent years, more and more studies have shown that gut-liver axis disorders, especially those caused by intestinal dysbiosis, intestinal barrier dysfunction, abnormal liver immune function, and bile acid metabolism disorders, play an important role in the occurrence and development of sepsis. This review describes the research progress of gut-liver axis disorders in the pathogenesis of sepsis for providing new ideas for clinical treatment.
ABSTRACT
Objective To investigate the effects of cytokines on the expression of angiotensin Ⅱ type 1 receptor (AT1R) in vascular smooth muscle cells (VSMCs) in rats. Methods Primary cultured VSMCs from SD rat thoracic aorta were cultured in serum-free DMEM for 24 h, and then in DMEM supplemented with 10% fetal bovine serum for another 12 h. The cultured VSMCs were randomly divided into 5 groups (n =6 each): control group (group C); 10% cytokine group (group L); 50% cytokine group (group N); 100% cytokine group (group H) and L-arginine methy ester (L-NAME), an inhibitor of nitric oxide synthase) group. In group C, the cellswere cultured continuously for 12 h. In L, N and H groups, 10%, 50% and 100% cytokines (IL-1β 50 ng/ml +TNF-α 100 ng/ml + IFN-γ 500 ng/ml) were added to the culture medium respectively and the cells were then incubated for 12 h. In group L-NAME, 100% cytokines + L-NAME 5 mmol/L were added to the culture medium and the cells were then incubated for 12 h. The expression of AT1R mPNA and protin was determined by RT-PCR and Western blot respectively.Results Cytokines down-regulated AT1R mRNA and protein expression in a concentration-dependent manner (P ＜ 0.05 or 0.01). L-NAME reversed cytokines-induced changes in AT1R mRNA and protein expression ( P ＜ 0.01). Conclusion Cytokines can down-regulate the expression of AT1R in rat VSMCs and the mechanism is related to the NO synthesis.
ABSTRACT
Objective To investigate the effects of antioxidant on the gene expression of ?1-adrenergic receptors (AR) during endotoxic shock. Methods Forty male SD rats weighing 200-250 g were anesthetized with intraperitoneal (i.p.) pentobarbital. The animals kept spontaneous breathing. Femoral artery and vein were cannulated for BP monitoring and drug administration. The animals were randomly divided into 5 groups ( n = 8 each) : (1) control group; (2) LPS group received IPS 15 mg?kg-1 i.v. ; (3) LPS + propofol group received at 1h after LPS a bolus of propofol 10mg?kg-1 i.v. followed by continuous infusion of propofol at 10 mg?kg-1?h-1; (4) LPS + uric acid (UA) group received uric acid 200 mg i.p. 1 h after LPS and (5) LPS + melatonin (MLT) group received MLT 10 mg?kg-1 i.p. 1h after LPS. The animals were killed at 6 h after LPS. Total RNA was extracted from the heart, aorta, vein, lung, liver and kidney. ?1A-,?1B-,?1D- AR mRNA and ?-actin mRNA were measured using reverse transcription polymerase chain reaction (RT-PCR) .Results The expression of ?1A-AR and ?1B-AR mRNA in all the organs and the ?1D-AR mRNA expression in aorta, liver, lung and kidney were strongly down-regulated in LPS group. In group 3 (LPS + propofol) the expression of ?1A-AR mRNA in the lung and kidney, the ?1B-AR mRNA expression in all of the organs and ?1D-AR mRNA expression in aorta, liver, lung and kidney were significantly increased as compared with LPS group. There was no significant difference in ?1-AR mRNA expression between LPS group and LPS + MLT group. The expression of ?1A-AR mRNA in kidney, the ?1B-AR mRNA expression in all of the organs except the lung and the ?1D-AR mRNA expression in aorta, liver, lung and kidney were significantly higher in LPS + UA group than in LPS group. Conclusion Circulatory failure induced by endotoxic shock is related to the down-regulation of ?1-AR gene expression. The therapeutic effects of antioxidant on the endotoxic shock is partly due to up-regulation of ?1-AR gene expression.