ABSTRACT
Chronic atrophic gastritis （CAG） is a common and intractable disease in the digestive system characterized by the reduction or disappearance of gastric mucosal glands. The intestinal metaplasia or dysplasia in CAG is called precancerous lesion， which greatly increases the risk of cancerization. Dysactivation of nucleotide-binding oligomerization domain-like receptor protein 3 （NLRP3） inflammatory corpuscles can release a large number of inflammatory factors， induce inflammatory cascade reactions， and participate in the process of many diseases. As reported， the dysactivation of NLRP3 inflammatory corpuscles can cause long-term chronic inflammatory infiltration of gastric mucosa and induce the development of CAG. Mitochondrial dysfunction plays an important role in the activation of NLRP3 inflammatory corpuscles. The accumulation of reactive oxygen species （ROS） produced by mitochondrial dysfunction is the key to activating NLRP3 inflammatory corpuscles. Professor LIU Youzhang put forward the theory of "spleen-mitochondrion correlation"， which holds that the spleen mainly transports water and grains， generates qi and blood， transports nutrients to the whole body， and supplies energy and materials needed by the body. Adenosine triphosphate （ATP） generated by mitochondria through the circulation of tricarboxylic acid is the main energy source of the human body. The view that both of them serve as human energy processing plants coincides in terms of physiology. Pathologically， spleen deficiency is associated with mitochondrial oxidative phosphorylation dysfunction. Pathological products such as dampness， turbidity， phlegm， and blood stasis due to failure in transportation because of spleen deficiency are consistent with metabolites generated by mitochondrial dysfunction. Based on the theory of "spleen-mitochondrion correlation"， this study discussed the pathogenesis of CAG in traditional Chinese medicine （TCM）， analyzed the relationship between NLRP3 inflammatory corpuscles and the pathogenesis of CAG， and proposed that the activation of NLRP3 inflammatory corpuscles by mitochondrial dysfunction was the modern biological basis of the pathogenesis of spleen deficiency in CAG. The spleen-strengthening method may be related to improving the mitochondrial function and inflammatory response of patients with CAG and alleviating the damage of gastric mucosa， providing a new idea for TCM in the prevention and treatment of CAG.
ABSTRACT
OBJECTIVE@#To observe the effect of acupuncture at "Baihui" (GV 20) through "Qubin" (GB 7) on NLRP3 inflammatory corpuscle in rats with intracerebral hemorrhage (ICH), and to explore the action mechanism of acupuncture on promoting the recovery of neural function in rats with ICH.@*METHODS@#Forty SPF six-week-old male SD rats were randomly divided into a sham operation group, a model group, a non-acupoint group and an acupuncture group, 10 rats in each group. The rats in the model group, non-acupoint group and acupuncture group were intervened with autologous blood injection to prepare ICH model, while the rats in the sham operation group were only intervened with operation but not injection with autologous blood. About 3 hours after the establishment of the model, the rats in the acupuncture group were intervened with acupuncture at "Baihui" (GV 20) through "Qubin" (GB 7), once every 12 hours, for 7 days; the rats in the non-acupoint group were intervened with acupuncture at the non-acupoint [parallel to the "Baihui" (GV 20), 1 cm next to the midline] on the affected side, and other treatment was the same as the acupuncture group. At the end of the intervention, the composite nerve function score of each group was evaluated; the histomorphology of the hemorrhage penumbra was observed by HE staining; the expression of NLRP3 inflammatory corpuscle in the brain was detected by immunohistochemistry; the relative protein expression levels of NLRP3, interleukin-1β (IL-1β) and interleukin-18 (IL-18) in brain were detected by the method of Western blot.@*RESULTS@#Seven days into intervention, compared with the sham operation group, each item score and total score of composite nerve function in the model group were significantly reduced (<0.01, <0.05). There was edema and karyopyknosis in brain neuron as well as necrocytosis and inflammatory cell infiltration in the model group. Compared with the model group and the non-acupoint group, the total score of composite nerve function and the scores of symmetrical movement of limbs (LS) and proprioception of tentacles (VP) in the acupuncture group were increased (<0.01, <0.05), and the cell necrosis and inflammatory cell infiltration were relieved. Compared with the sham operation group, NLRP3 inflammatory corpuscle expression and the relative protein expression levels of NLRP3, IL-1β and IL-18 in brain tissue in the model group were increased (<0.01); compared with the model group and the non-acupoint group, NLRP3 inflammatory corpuscle expression and the relative protein expression levels of NLRP3, IL-1β and IL-18 in brain tissue in the acupuncture group were reduced (<0.01).@*CONCLUSION@#Acupuncture at "Baihui" (GV 20) through "Qubin" (GB 7) could downregulate the expression of NLRP3, IL-1β and IL-18 in the brain tissue of ICH rats, inhibit the inflammatory response, and promote the recovery of neural function.
Subject(s)
Animals , Male , Rats , Acupuncture Points , Acupuncture Therapy , Brain , Cerebral Hemorrhage , Metabolism , Therapeutics , Interleukin-18 , Metabolism , Interleukin-1beta , Metabolism , NLR Family, Pyrin Domain-Containing 3 Protein , Metabolism , Rats, Sprague-DawleyABSTRACT
AIM: To study the mechanism of minocycline (Mino) in inhibiting inflammatory corpuscle NLRP3-mediated pyroptosis and improving cognitive ability in Alzheimer's disease. METHODS: Lipopolysaccharide (LPS) was used to induce PC12 to construct a model of neuronal pyroptosis. The cells were divided into control group, LPS group and LPS+Mino group. CCK-8 assay was used to detect cell viability, flow cytometry was used to detect apoptotic level, and Western blot was used to detect the levels of key proteins NLRP3, ASC, Caspase-1 and pro-Caspase-1 in NLRP3 corpuscles, as well as the levels of GSDMD and p30-GSDMD. Enzyme-linked immunosorbent assay was used to detect the expression of interleukin-1β, interleukin-18 and tumor necrosis factor-α in culture medium. APP-PS1 mice were randomly divided into control group and experimental group. The experimental group was given intragastric administration of minocycline 50 μg. The cognitive and memory abilities of mice were tested by Morris test before and 3 weeks after administration. The expressions of NLRP3, ASC, Caspase-1 and pro-Caspase-1 in hippocampal CA3 region were detected after execution, and the expressions of inflammatory factors such as IL-1β, IL-18 and TNF-α were detected. RESULTS: Minocycline could inhibit LPS-induced pyroptosis. Cell viability in LPS+Mino group was significantly higher than that in LPS group, and the apoptotic rate was significantly lower than that in LPS group (P<0.05). The expression of NLRP3, ASC and Caspase-1 in LPS+Mino group was lower than that in LPS group, while the expression of p30-GSDMD was lower than that in LPS group, and GSDMD was higher than that in LPS group. The levels of IL-1β, IL-18 and TNF-α in culture medium were lower than those in LPS group, with significant difference (P<0.05). In animal experiments, minocycline could significantly improve the cognitive ability of mice. In Morris experiment, the latency of mice was shortened, which had statistical significance compared with the control group (P<0.05). At the same time, the number of times of mice crossing the platform increased significantly compared with the control group (P<0.05). The expression of key proteins NLRP3, ASC and Caspase-1 in NLRP3 corpuscle of mice in experimental group was lower than that in control group, while the expression of pyroptosis executive protein p30-GSDMD was lower than that in control group, GSDMD was higher than that in control group, and the levels of inflammatory factors IL-1β, IL-18 and TNF-α were lower than that in control group (P<0.05). CONCLUSION: Minocycline can inhibit the activation of NLRP3 corpuscle and the occurrence of neuronal pyroptosis, and improve the cognitive ability of mice with Alzheimer's disease.
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Objective@#To investigate the expression and significance of NLRP3/IL-1β/TGF-β1 signal axis in a rat model of silicosis and pulmonary fibrosis.@*Methods@#Eighty healthy Wistar male rats of SPF grade were randomly divided into 4 groups: high (100 mg/ml) , medium (50 mg/ml) , low (25 mg/ml) concentration SiO2 dusting group and normal negative control. Group, 20 in each group. Five rats were sacrificed at 7 d, 14 d, 28 d and 56 d after SiO2 dusting. The degree of alveolitis and the degree of pulmonary fibrosis were observed. The enzyme-linked immunosorbent assay (ELISA) was used to detect IL-1β in lung tissue. The expressions of NLRP3 and Caspase-1 in lung tissue of rats were detected by Western Blot.@*Results@#The alveolitis score and fibrosis degree of the rats in the dust-receiving group were significantly higher than those in the control group at 7 d, 14 d, 28 d and 56 d, and the difference was statistically significant (P<0.01) . The concentrations of IL-1β, IL-18 and TGF-β1 in 14 d, 28 d and 56 d were significantly higher than those in the control group (P<0.01) . The expressions of NLRP3 and Caspase-1 in lung tissue of rats exposed to dust were 7 d and 14 d, 28 d, 56d were higher than the control group (P<0.01) ; the expression levels of NLRP3, Caspase-1, IL-1β, IL-18 and TGF-β1 in the low, medium and high concentration SiO2 dusting group were 7 d, 14 d and The difference between the two groups was statistically significant (P<0.05) , and both showed a time-effect relationship with the increase of dusting time.@*Conclusion@#NLRP3 and its downstream factors Caspase-1, IL-1β, IL-18 and TGF-β1 are highly expressed in the lung tissue of rats with silicosis and pulmonary fibrosis, suggesting that the NLRP3/IL-1β/TGF-β1 signal axis may be associated with silicosis. Pulmonary fibrosis has a close relationship and plays a role in the formation of silicosis.