| Background:Apoptosis is mediated by the presence of self-destruct mechanism in cells, helping the body to remove aging and abnormal cells, and playing an important role in the maintenance of a variety of cellular functions. It can be in nature, also can be caused by chemotherapy and radiotherapy-induced.Inflammasome is composed of a variety of protein complexes, which molecular weight is about 700 KDa. Inflammasome can regulate the activation of caspase-1 and promote maturity of pro-IL-1β, and pro-IL-18 in the process of natural immune defense, also regulate caspase-1-dependent form of programmed cell death, cell death induced stress in inflammatory and pathological conditions. Thus, inflammatory bodies play an important role in the apoptotic process in inflammation.Cysteinyl aspartate specific proteinase is a group of protease with similar structure which exists in the cytoplasm. Also closely related to the apoptosis of nucleated cells, and participate in the regulation of cell growth and differentiation. Caspase-1 is one of the earliest apoptosis protease to be found, mainly involved in the regulation of the activation process. Caspase-1 can be directly involved in cascade, with circulation amplification effect, is important in Fas-mediated apoptosis cascade, other factors can be activated as the active enzyme hydrolyzed form, and then ADP-ribose polymerase cleavage, resulting in DNA fragmentation and apoptosis.Interleukin is produced by a variety of cells and can work in many cells, a class of cytokines involved in regulating a variety of cellular behavior. IL-1β is also known as former inflammation cytokines, mainly secrete by mononuclear macrophages, can stimulate degranulation of monocytes. IL-1β plays an important role in inflammation-associated periodic syndrome, genetic diseases, and autoimmune diseases related on multiple genes, some anti-IL-1β disease have been well controlled. In other studies, caspase-1 and IL-1β may jointly participate in inflammation and apoptosis in a variety of organs and tissues.Objective:To investigate the protective effect and mechanism of lidocaine associated lipopolysaccharide-induced inflammation in the process.Methods:Monolayer cultured mouse macrophages (raw264.7) in six-well plates were randomly divided into four groups:control group (group C), lidocaine group (group L), lipopolysaccharide (LPS) group (group LPS), lidocaine+lipopolysaccharide group (group L + LPS). Apoptosis rates were measured by lactate dehydrogenase cytotoxicity assay kit. The expressions of mRNA in caspase-1, IL-1β were measured by Realtime PCR (RT-PCR) assay cell. The expressions of protein of caspase-1, IL-1 were measured by enzyme-linked immunosorbent assay (ELISA).Results:1. Compared with group C, the apoptosis rate, mRNA expression and protein expression of caspase-1, IL-1β of group L were no significant difference;2. Compared with group C, apoptosis rate, mRNA expression levels and protein expression levels of caspase-1, IL-1β of group LPS were significantly increased (P <0.05);3. Compared with the LPS group, apoptosis rate of group L+LPS was significantly reduced (P<0.05), mRNA and protein expression levels of caspase-1, IL-1β expression levels were significantly lower (P<0.05).Conclusion:Lidocaine can reduce apoptosis in LPS-induced inflammatory response of murine macrophages. Protective effects of lidocaine on tissue inflammation may be related to inhibition of caspase-1, IL-1β such as overexpression.Significance:This study examined the effects of lidocaine on the immune system, verifies the anti-inflammatory effects of lidocaine, provides a theoretical basis for the clinical application of lidocaine. The protective effect of lidocaine on immune function may be related to inhibition of immune cell apoptosis, reduction of inflammatory cytokine release related assumptions. It provides a new way for clinical anti-inflammatory treatment, but the exact mechanism of this hypothesis is not yet clear, it will be further studied. |
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