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Pyroptosis is a newly discovered programmed cell death that can lead to inflammatory response, its occurrence depends on the sequential activation of inflammatory bodies and caspase, and then the pore-forming generated by the fragmentation of gasdermin D and its cell membrane polymerization. Pyroptosis is mainly comprised of the pathway that depends on caspase-1 activated by flammasomes and the non-classical pathway that depends on caspase-4/5/11 activated by cytoplasmic lipopolysaccharide. As an important mechanism mediating the inflammatory response of the body, pyroptosis plays an irreplaceable role in the body's response to noxious stimuli, which is closely related to many diseases such as nervous system diseases, cardiovascular system diseases and tumors. Recent studies have found that pyroptosis also plays a key role in the occurrence of intestinal ischemia-reperfusion (II/RI). This paper reviews the molecular characteristics, mechanism of pyroptosis and its relationship with II/RI in recent years, in order to provide theoretical basis for the prevention and treatment of II/RI.
RESUMO
Objective:To evaluate the effect of astaxanthin on neuropathic pain in rats and the role of spinal heme oxygenase-1 (HO-1).Methods:Seventy-two SPF-grade healthy adult male Sprague-Dawley rats, weighing 200-250 g, in which intrathecal catheters were successfully implanted, were divided into 6 groups ( n=12 each) by a random number table method: blank control group (group C), sham operation group (Sham group), neuropathic pain (NP) group, NP plus dimethyl sulfoxide (DMSO) group (NP + DMSO group), NP plus astaxanthin group (NP + AST group) and NP plus zinc protoporphyrin plus astaxanthin group (NP+ ZnPP+ AST group). NP was induced by chronic constriction injury in anesthetized rats.In Sham group, the sciatic nerve was only isolated without ligation.At 5 days after establishing the model, 0.5% DMSO 10 μl was intrathecally injected in NP+ DMSO group, astaxanthin 1 μg (dissolved in 10 μl DMSO) was intrathecally injected in NP+ AST group, HO-1 inhibitor zinc protoporphyrin 24 μg (dissolved in 10 μl DMSO) was intrathecally injected, and 3 h later astaxanthin 1 μg (dissolved in 10 μl DMSO) was intrathecally injected in NP+ ZnPP+ AST group.Injection was given once a day for 10 consecutive days in the 3 groups mentioned above.The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 1 day before establishing the model and 3, 7 and 14 days after establishing the model.The rats were sacrificed at 14 days after establishing the model, and the L 4-6 lumbar segments of the spinal cord were removed for determination of the contents of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), superoxide dismutase (SOD) and glutathione peroxidase (GHS-PX)(by enzyme-linked immunosorbent assay) and expression of HO-1 (by Western blot). Results:Compared with group C and group Sham, the MWT was significantly decreased and TWL was shortened at each time point after establishing the model, the contents of TNF-α and IL-1β were increased, and the expression of HO-1 was up-regulated in the other four groups, the SOD and GSH-PX contents were significantly decreased in NP group, NP+ DMSO group and NP+ ZnPP+ AST group, and the SOD and GSH-PX contents were significantly increased in NP+ AST group ( P<0.05). Compared with NP group, the MWT was significantly increased and TWL was prolonged at 7 and 14 days after establishing the model, the contents of TNF-α and IL-1β were decreased, and the expression of HO-1 was up-regulated in NP+ AST group, the expression of HO-1 was down-regulated in NP+ ZnPP+ AST group ( P<0.05), and no significant change was found in the parameters mentioned above in NP+ DMSO group ( P>0.05). Compared with NP+ AST group, the MWT was significantly decreased and TWL was shortened at 7 and 14 days after establishing the model, the contents of SOD and GSH-PX were decreased, the contents of TNF-α and IL-1β were increased, and the expression of HO-1 was down-regulated in NP+ ZnPP+ AST group ( P<0.05). Conclusion:Astaxanthin can reduce NP in rats, and the mechanism is related to up-regulating the expression of HO-1 in the spinal cord and inhibiting oxidative stress and inflammatory responses.