ABSTRACT
Gut microbiota dysbiosis is an avenue for the promotion of atherosclerosis (AS) and this effect is mediated partly via the circulating microbial metabolites. More microbial metabolites related to AS vascular inflammation, and the mechanisms involved need to be clarified urgently. Paeonol (Pae) is an active compound isolated from Paeonia suffruticoas Andr. with anti-AS inflammation effect. However, considering the low oral bioavailability of Pae, it is worth exploring the mechanism by which Pae reduces the harmful metabolites of the gut microbiota to alleviate AS. In this study, ApoE-/- mice were fed a high-fat diet (HFD) to establish an AS model. AS mice were administrated with Pae (200 or 400 mg·kg-1) by oral gavage and fecal microbiota transplantation (FMT) was conducted. 16S rDNA sequencing was performed to investigate the composition of the gut microbiota, while metabolomics analysis was used to identify the metabolites in serum and cecal contents. The results indicated that Pae significantly improved AS by regulating gut microbiota composition and microbiota metabolic profile in AS mice. We also identified α-hydroxyisobutyric acid (HIBA) as a harmful microbial metabolite reduced by Pae. HIBA supplementation in drinking water promoted AS inflammation in AS mice. Furthermore, vascular endothelial cells (VECs) were cultured and stimulated by HIBA. We verified that HIBA stimulation increased intracellular ROS levels, thereby inducing VEC inflammation via the TXNIP/NLRP3 pathway. In sum, Pae reduces the production of the microbial metabolite HIBA, thus alleviating the ROS/TXNIP/NLRP3 pathway-mediated endothelial inflammation in AS. Our study innovatively confirms the mechanism by which Pae reduces the harmful metabolites of gut microbiota to alleviate AS and proposes HIBA as a potential biomarker for AS clinical judgment.
Subject(s)
Animals , Mice , Atherosclerosis/drug therapy , Diet, High-Fat , Endothelial Cells , Inflammation/drug therapy , Mice, Inbred C57BL , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Reactive Oxygen SpeciesABSTRACT
Objective To evaluate the effect of minimally invasive therapy for treating intraventricular hemorrhage.Methods The minimally invasive therapy with unilateral or bilateral drainage were received according to quantity and shape of intraventricular hemorrhage.Results It was operated 22 cases with unilateral drainage and 28 cases with bilateral drainage in the 50 cases intraventricular hemorrhage.Death was 3 cases and mortality rate was 6% in the minimally invasive therapy.ADL1 15 cases(30%),ADL2 18 CRSeS(36%),ADL3 8 cases(16%),ADLA4 cases(8%),ADL5 2 cases(4%)in leave hospital.Conclusion Minimal invasive therapy of intraventrieular hemorrhage has great superiority,such as it can operate simple,trauma mild,decrease complications and enhance curative effect.It can generalize in the basic hospital.
ABSTRACT
Objective - To analyze the relation between classes and prognosis of the brain.stem hemorrhage.Methods 37 patients with spontaneous brainstem hemorrhage were divided into three groups according to con-sciousness and breathing function: Ⅰ group 13 cases with consciousness; Ⅱ group 11 cases without consciousness; Ⅲgroup 13 cases without consciousness and respiration, according to the classes, using different ways and means. Re-suits Ⅰ group 13 cases survival in 13 cases; Ⅱ group 10 cases survival and 1 case death in 11 cases; Ⅲ group 1 case survival and 12 cases death in 13 eases. Conclusion The classes of the brain.stem hemorrhage is propitious to select therapeutic measure and prognostic estimate. The intensive care and the surgery can reduce mortality rate.