甘氨酸偶联皮质醇抗Compound 48/80刺激大鼠急性过敏反应的作用研究

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目的:观察甘氨酸偶联皮质醇(HG)对Compound 48/80(C48/80)刺激大鼠急性过敏反应的影响,以期为后期深入探讨糖皮质激素非基因组机制建立有效研究工具。方法:将60只雄性SD大鼠随机分为4组:急性过敏模型组(腹腔注射C48/80+对照溶剂,n=15)、皮质醇(GC)干预组(腹腔注射C48/80+GC,n=15)、HG干预组(腹腔注射C48/80+HG,n=15)、空白对照组(腹腔注射等量生理盐水,n=15)。造模组及各干预组分别在腹腔注射C48/80 5 min后分别给予腹腔注射对照溶剂(等量无水乙醇,为GC及HG的稀释溶剂)、GC或HG,之后每5 min监测大鼠肛温及平均动脉压(MAP),腹腔注射C48/80后30 min时处死大鼠,取大鼠咽喉组织及肺组织,多聚甲醛固定切片后观察组织形态;同时摘眼球取血,分离血清,采用酶联免疫吸附实验(ELISA)测定血清中组胺含量。结果:与空白对照组相比,造模组大鼠肛温及平均动脉压呈持续降低趋势,C48/80刺激可诱发大鼠咽喉及肺组织水肿、肺泡损坏及炎性细胞浸润,大鼠血清中组胺水平较对照组显著升高(P<0.05);较造模组各干预组均可减轻造模诱发的上述过敏反应(P<0.05),但HG干预组较GC干预组促进大鼠肛温降低恢复起效时间快、复温效率高(P<0.05),HG干预组减弱大鼠平均动脉压持续性降低趋势较GC干预组效果明显(P<0.05);HG干预组显著减轻C48/80刺激导致的咽喉及肺组织水肿、肺泡损坏及炎性细胞浸润;HG干预组能显著抑制C48/80刺激导致的血清组胺升高水平(P<0.05),但HG干预组与GC干预组抑制效果无明显差异(P>0.05)。结论:HG能够快速抑制C48/80刺激诱导的大鼠急性过敏反应;能够显著抑制肥大细胞组胺的释放;HG可能通过非基因组作用快速抑制肥大细胞的脱颗粒,抑制炎性介质组胺的释放,从而抑制免疫炎症反应,发挥抗过敏及抗炎症效应,从而为研究糖皮质激素非基因组机制提供了有效的研究工具。 AIM: To observe the effect of glycine-coupled cortisol (HG) on acute hypersensitivity in Compound 48/80 (C48 / 80) -stimulated rats, in order to establish an effective research tool for further exploration of non-genomic mechanisms of glucocorticoid in the later period. Methods: Sixty male Sprague-Dawley rats were randomly divided into 4 groups: acute allergic model group (intraperitoneal injection C48 / 80 + control solvent, n = 15), Cortisol intervention group n = 15), HG intervention group (intraperitoneal injection of C48 / 80 + HG, n = 15), blank control group (intraperitoneal injection of normal saline, n = 15). Rats in model group and each intervention group were injected intraperitoneally with control solvent (equal amount of absolute ethanol, diluted solvent of GC and HG), GC or HG respectively after intraperitoneal injection of C48 / 80 for 5 min, and rats were monitored every 5 min Rectal temperature and mean arterial pressure (MAP), 30 min after intraperitoneal injection of C48 / 80, the rats were sacrificed, the throat tissues and lungs of rats were taken, and the paraformaldehyde fixed sections were observed for histomorphology; , The serum histamine content was measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared with the blank control group, the rectal temperature and mean arterial pressure of rats in the model group continued to decrease. C48 / 80 stimulation induced throat and lung tissue edema, alveolar damage and inflammatory cell infiltration in rats. Serum (P <0.05). Compared with the control group, the levels of histamine were significantly increased (P <0.05). Compared with the intervention group, all the intervention groups could alleviate the hypersensitivity reaction induced by modeling (P <0.05) The remission rate of rectal temperature was faster and the rate of rewarming was higher (P <0.05). Compared with GC group, HG intervention group decreased the mean decrease of mean arterial pressure significantly (P <0.05); HG intervention group significantly reduced C48 (P <0.05). However, HG intervention group was significantly inhibited by C48 / 80 stimulus (P <0.05), but HG intervention group and GC intervention There was no significant difference between the two groups (P> 0.05). CONCLUSION: HG can rapidly inhibit the acute hypersensitivity reaction induced by C48 / 80 stimulation in rats and can significantly inhibit the release of histamine from mast cells. HG may inhibit the degranulation of mast cells and inhibit the release of histamine in inflammatory mediators through non-genomic effects , Thereby inhibiting the immune inflammatory response, anti-allergic and anti-inflammatory effect, thus providing an effective research tool for the study of non-genomic mechanisms of glucocorticoid.
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