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Liver injury caused by acetaminophen (AP) overdose is a leading public health problem. Although AP-induced liver injury is well recognized as the formation of N-acetyl-p-benzoquinone (NAPQI), a toxic metabolite of AP, resulting in cell damage, emerging evidence indicates that AP-induced liver injury is also associated with gut microbiota. However, the gut microbiota-involved mechanism remains largely unknown. In our study, we found that vancomycin (Vac) pretreatment (100 mg/kg, twice a day for 4 days) attenuated AP-induced liver injury, altered the composition of gut microbiota, and changed serum metabolic profile. Moreover, we identified Vac pretreatment elevated cecum and serum 2-hydroxybutyric acid (2-HB), which ameliorated AP-induced cell damage and liver injury in mice by reducing AP bioavailability and elevating GSH levels. Our current results revealed the novel role of 2-HB in protecting AP-induced liver injury and add new evidence for gut microbiota in affecting AP toxicity.
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Objective To evaluate the effects of hyperbaric oxygen post-conditioning on the expression of P2X4 receptors in the spinal dorsal horn and hippocampus of rats with neuropathic pain (NP).Methods Seventytwo male Sprague-Dawley rats,aged 8-10 weeks,weighing 300-350 g,were randomly divided into 3 groups (n =24 each) using a random number table:sham operation group (group S),NP group and hyperbaric oxygen postconditioning group (group H).NP was induced by chronic constrictive injury.The rats in group H underwent hyperbaric oxygen treatment once a day for 7 consecutive days starting from 1 day after NP was successfully induced.After the rats were placed in the hyperbaric oxygen chamber,the pressure was increased at a rate of 10 kPa/min until the hyperbaric oxygen was at 2.0 atmosphere absolute,and maintained at this level for 60 min,and then the pressure was decreased at a rate of 10 kPa/min until the normal pressure was reached.The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 1 day before NP was induced and 1,3,7 and 14 days after NP was induced.After the end of measurement,6 rats were randomly chosen from each group and then sacrificed and the L4-6 segments of the spinal cord and hippocampal tissues were removed for determination of the expression of P2X4 receptors (by immunohistochemistry).Results Compared with group S,the MWT was significantly decreased,TWL was shortened,and P2X4 receptor expression in the spinal dorsal horn and hippocampus was up-regulated in NP and H groups.Compared with group NP,the MWT was significantly increased and TWL was prolonged,and P2X4 receptor expression in the spinal dorsal horn and hippocampus was down-regulated in group H.Conclusion Hyperbaric oxygen post-conditioning mitigates NP by down-regulating the expression of P2X4 receptors in the spinal dorsal horn and hippocampus of rats.
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AIM: To decide the effect that selected siRNA degrades mRNA of IL-1? specifically and suppression of its expression after connected with target site with homology complementary sequence. METHODS: Synthesized DNA expression box aimed directly at target site through PCR reaction in vivo was purified, and transfected into lymphocytes stimulated by LPS. siRNA was transcribed by cellular endogenous RNA polymerase Ⅲ and then evoke the degradation of target mRNA. After 48 hours of transfection, the cell culture supernatant was collected and the concentration of IL-1? was assayed using ELISA. RESULTS: Compared with blank-control and negative-control, selected sequence decreased the expression of IL-1?. Rate of the suppression was about 15%. CONCLUSION: RNAi technology produces specific interference effect in mouse spleen lymphocytes in original culture and inhibits the excretion of IL-1?.