Project description:Ischemia-reperfusion (I/R) injury refers to a new injury caused by reperfusion after the restoration of ischemic tissue or organ blood supply. Salvianic acid A (danshensu) is a primary active ingredient extracted from Salvia miltiorrhiza. It has a protective function against I/R injury in the cardiovascular system, brain, liver, kidney, gastrointestinal tract, and other organs. This article reviews evidence of the protective effects of Salvianic acid A and its potential mechanisms of action in organ I/R injury protection. The aim of this review is to investigate the role of Salvianic acid A in the treatment of I/R injury, providing a reference resource that could facilitate subsequent studies.
Project description:This study was designed to investigate the protective effect and mechanism of Sufentanil on acute lung injury in septic mice based on network pharmacology and animal experiments, and to provide new ideas for clinical treatment. To this end, a protein-protein interaction (PPI) network for common targets was first constructed with Swiss Target Prediction Database, GeneCards Database, Draw Venn Diagram Software, STRING 11.5 Database, Cytoscape 3.10.0 Software and Metascape Database, and then key targets were subject to enrichment analysis by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) to obtain the key targets of Sufentanil for the treatment of pulmonary sepsis, and then verified by animal experiments. A sepsis model was constructed by cecal ligation and puncture (CLP) in this study, and lung tissues and bronchoalveolar lavage fluid (BALF) were taken from each group of mice. The morphological changes of lung tissues and apoptosis were observed by HE and TUNEL staining, the content of inflammatory factors in the lung tissues was detected by ELISA, and the expression of proteins, such as p-JAK2 and p-STAT3, was detected in the lung tissues by Western blotting. According to the results of network pharmacology, a total of 40 common targets of were screened out for Sufentanil and pulmonary sepsis, and GO enrichment analysis involved 1,483 biological processes (BPs), 84 cellular components (CCs) and 125 molecular functions (MFs); KEGG enrichment analysis identified 137 signaling pathways with p < 0.05 such as JAK-STAT. According to the results of animal experiments, compared with the control group, mice in the model group had severe lung tissue injury and elevated expression of relevant inflammatory factors in lung tissue. Compared with the model group, CLP + Sufentanil group showed reduced pathomorphologic lesions, lower expression of inflammatory factors and apoptosis level, as well as lower expression of p-JAK2 and p-STAT3 proteins in lung tissue. The results of animal experiments were consistent with network pharmacology. In summary, Sufentanil may improve lung injury in septic mice by inhibiting the JAK2-STAT3 signaling pathway, which provides a basis for research on the mechanism of Sufentanil on pulmonary sepsis and clinical treatment.
Project description:BackgroundAlthough many sepsis treatments have shown efficacy in acute animal models, at present only activated protein C is effective in humans. The likely reason for this discrepancy is that most of the animal models used for preclinical testing do not accurately replicate the complex pathogenesis of human sepsis. Our objective in this study was to develop a clinically applicable model of severe sepsis and gut ischemia/reperfusion (I/R) that would cause multiple organ injury over a period of 48 h.Materials and methodsAnesthetized, instrumented, and ventilated pigs were subjected to a "two-hit" injury by placement of a fecal clot through a laparotomy and by clamping the superior mesenteric artery (SMA) for 30 min. The animals were monitored for 48 h. Wide spectrum antibiotics and intravenous fluids were given to maintain hemodynamic status. FiO(2) was increased in response to oxygen desaturation. Twelve hours following injury, a drain was placed in the laparotomy wound. Extensive hemodynamic, lung, kidney, liver, and renal function measurements and serial measurements of arterial and mixed venous blood gases were made. Bladder pressure was measured as a surrogate for intra-peritoneal pressure to identify the development of the abdominal compartment syndrome (ACS). Plasma and peritoneal ascites cytokine concentration were measured at regular intervals. Tissues were harvested and fixed at necropsy for detailed morphometric analysis.ResultsPolymicrobial sepsis developed in all animals. There was a progressive deterioration of organ function over the 48 h. The lung, kidney, liver, and intestine all demonstrated clinical and histopathologic injury. Acute lung injury (ALI) and ACS developed by consensus definitions. Increases in multiple cytokines in serum and peritoneal fluid paralleled the dysfunction found in major organs.ConclusionThis animal model of Sepsis+I/R replicates the systemic inflammation and dysfunction of the major organ systems that is typically seen in human sepsis and trauma patients. The model should be useful in deciphering the complex pathophysiology of septic shock as it transitions to end-organ injury thus allowing sophisticated preclinical studies on potential treatments.
Project description:BackgroundThis study aims to evaluate the inhibitory effect of curcumin (Cur) on the progression of septic acute kidney injury (SAKI), in order to improve the survival rate in this patient population.MethodsAcute kidney injury (AKI) was induced by cecal ligation perforation (CLP) in Sprague-Dawley (SD) rats. Using this AKI animal model, the survival rate of the rats was evaluated at different time points after Cur treatment to explore whether Cur can improve survival in an animal model of AKI. The expression levels of inflammatory factors (NF-κB, TNF-α, and IL-10), organ injury markers [urea nitrogen (UN), creatinine (Cr), alanine aminotransferase (ALT), aspartate aminotransferase (AST), amylase, creatine kinase (CK), and lactate dehydrogenase (LDH)], and disease progression markers [neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and cystatin-C (CysC)] were determined using an enzyme-linked immunosorbent assay (ELISA).ResultsThe serum levels of UN, Cr, NF-κB, ALT, AST, amylase, CK, LDH, inflammatory factors TNF-α and IL-10, and markers of early diagnosis of SAKI (NGAL, CysC, KIM-1) were significantly lower in the curcumin group than those in the placebo group (P<0.05). In addition, serum levels of TLR9 and its downstream molecules MyD88, IRF5, and IRF7 in the curcumin group were significantly lower than those in the placebo group (P<0.05). The application of TLR9-specific inhibitors to experimental rats led to similar results as those obtained in the curcumin group, whose detection indexes were significantly lower than those in the placebo treatment group (P<0.05).ConclusionsGiven the excellent performance of Cur in anti-tumor, anti-oxidation, anti-inflammatory, and other clinical trials, it is very likely to be further developed as a potential drug for the clinical treatment of AKI.
Project description:1 We examined whether edaravone (Eda), a clinically available radical scavenger, directly protects cardiomyocytes from ischemia/reperfusion (I/R) injury, and whether the timing of its application is critical for protection. 2 Cardioprotective effects of edaravone were tested in the modified cell-pelleting model of ischemia and under exogenous oxidative stress (hydrogen peroxide: H2O2) in isolated adult rabbit ventricular cells. Cell death and reactive oxygen species (ROS) generation were detected using propidium iodide (PI) and DCFH-DA, respectively. These parameters were evaluated objectively using flow cytometory. 3 Hypoxia and reoxygenation aggravated the proportion of dead cells from 32.2+/-1.8% (Baseline) to 51.3+/-2.7% (Control). When 15 microm edaravone was applied either throughout the entire experiment (Through) or only at reoxygenation (Reox), cell death was significantly reduced to 39.9+/-1.8% (P<0.01 vs Control) and 43.3+/-2.5% (P<0.05 vs Control), respectively. In contrast, when edaravone was applied 10 min after reoxygenation, its protective effect disappeared. Cardioprotection by edaravone was more remarkable than that afforded by other free radical scavengers, such as ascorbate and superoxide dismutase (SOD). There is a positive correlation between the cardioprotective effect of edaravone and the extent of ROS reduction. 4 Edaravone blunted the H2O2-induced changes in electrical properties, and significantly prolonged the time to contracture induced by H2O2 in single ventricular myocytes. 5 Taken together, edaravone directly protects cardiomyocytes from I/R injury by attenuating ROS production, even when applied at the time of reoxygenation, suggesting that edaravone could be a potent cardioprotective therapeutic agent against hypoxia-reoxygenation injury.