RESUMO
Background: Sepsis is a common complication of severe trauma, burns, infection, or major surgery. This disease-related end-organ dysfunction results from systemic inflammatory response syndrome (SIRS). Acute kidney damage (AKI), also known as acute renal failure, is one of the most frequent and serious sequelae of sepsis. Nuclear transcription factor-κB (NF-κB) regulates the transcription of inflammation-related genes and operates as a mediator in the immune system. While parthenolide (PTL) has been reported to prevent harmful inflammatory reactions, its effects on sepsis-associated AKI are unknown. The current study investigates the effects of PTL in sepsis-associated AKI using cell and cecal ligation and puncture (CLP) models. Methods: Lipopolysaccharide (LPS)-stimulated rat glomerular mesangial cells were treated with 10 µM PTL. Inflammatory mediators, including TNF-α, IL-6, and IL-1ß, in the culture supernatants were measured by ELISA, and NF-κB levels were assessed by qPCR. After the generation of the septic CLP model, rats were intraperitoneally injected with 500 g/kg PTL and were euthanized after 72 h. Serum and kidney samples were analyzed. Results: TNF-α, IL-1ß, and IL-6 levels were elevated after LPS treatment of rat glomerular mesangial cells (p=0.004, p=0.002, and p=0.004, respectively) but were significantly reduced in the PTL treatment group (p ≤ 0.001, p=0.01, and p ≤ 0.001). NF-κB p65 levels were also increased after LPS treatment in this group and were reduced in the PTL treatment group. PTL treatment also reduced kidney damage after CLP induction, as shown by histological analysis and reductions in the levels of BUN, Cre, KIM-1, and NAGL. CLP-induced kidney inflammation together with increased levels of proinflammatory cytokines and inflammatory-related proteins. The elevated levels of renal TNF-α, IL-6, and IL-1ß were downregulated after PTL treatment. The PTL treatment also reduced the CLP-induced activation of NF-κB p65 in the damaged kidneys. Conclusion: PTL reduced inflammation induced by CLP-induced AKI in rat models and LPS-induced damage to glomerular mesangial cells by suppressing NF-κB signaling.
RESUMO
Background: Sepsis is defined as a host inflammatory response to infection that can result in end-organ dysfunction. One of the most common consequences of sepsis is acute kidney injury (AKI). Panax notoginseng powder (PNP) has been previously reported to protect against overactive inflammation process. However, the potential effect of PNP on septic AKI is poorly described. The current study was conducted to investigate the protective effects of PNP in septic AKI rats. Methods: A model of septic AKI was established on male SD rats by using the cecal ligation and puncture procedure. PNP was administrated by gavage after the cecal ligation and puncture (CLP) procedure, and the mice were sacrificed at 6, 12, and 72 h after induction of sepsis. The serum and kidney samples were collected and assayed for biochemical tests, histopathological staining, inflammation, and apoptosis-related gene/protein expression. In addition, 15 rats in each group were used to calculate the 7-day survival rate. Results: CLP-induced kidney injury was observed by the histopathological score, which markedly was attenuated by PNP treatment. Consistently, PNP intervention significantly alleviated the elevated levels of serum creatinine and blood urea nitrogen in CLP-induced sepsis rats. The CLP procedure also triggered proinflammatory cytokine production and increased the expression of various inflammation-related proteins in the kidneys. However, PNP inhibited the renal expression of IL-18, IL-1ß, TNF-α, and IL-6 to substantially improve inflammatory response. Mechanistically, CLP induced the increase of the NF-κB p65 level in the injured kidneys, while PNP notably inhibited the corresponding protein expression. Conclusion: PNP attenuated kidney inflammation to protect against CLP-induced septic AKI in rats via inhibiting the NF-κB signaling pathway.
RESUMO
OBJECTIVE: To evaluate the effect of venlafaxine on the cognitive impairment of learning and memory in rats with post-stroke depression (PSD) and to investigate its relationship with the expression of brain-derived neurotrophic factor (BDNF) in hippocampus. METHODS: Fifty male adult SD rats were randomly divided into control group, model group and three treatment groups (5,10, 20 mg*kg(-1) venlafaxine) with ten in each group. After the procedure of selective cerebral right middle artery embolism, a paradigm of continuous 3-week chronic unpredictable mild stress (CUMS) was used to induce PSD. Along with the course of CUMS the peritoneal injection at different dose levels of venlafaxine were performed once a day in PSD rats in a fixed time interval. Morris water maze test was applied to assess the spatial learning and memory function and immunohistochemical staining was used to detect the change of BDNF expression. RESULTS: The learning function decreased significantly in PSD rats compared with the control (P<0.05), as well as in spatial exploring time (14.2 s ± 4.8 s Compared with 45.9 s ± 4.5 s) and frequency of spanning platform (1.3 ± 0.3 Compared with 8.3 ± 1.1). Moreover,very fewer BDNF positive cells were found in CA3 area of hippocampus in model group in comparison with the control group (9.8 ± 3.2 Compared with 18.5 ± 4.7). After different dosage of venlafaxine treatment, the BDNF expression and cognition increased markedly. CONCLUSION: Venlafaxine can improve PSD-induced learning and memory dysfunction, possibly through the enhancement of the BDNF level in the CA3 area of hippocampus.
