Effects of rhubarb on the expression of glucocorticoids receptor and regulation of cellular immunity in burn-induced septic rats
Effects of rhubarb on the expression of glucocorticoids receptor and regulation of cellular immunity in burn-induced septic rats
复制标题
大黄对烧伤脓毒症大鼠糖皮质激素受体表达及细胞免疫调节的影响
DOI：
10.1097/cm9.0000000000000201
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发表时间：
2019-05-20
影响因子：
6.1
通讯作者：
Chen, De-Chang
中科院分区：
文献类型：
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作者：
Liu, Jiao;Li, Guang;Chen, De-Chang
背景资料：在脓毒症发生发展过程中，调节肿瘤组织糖皮质激素受体（GR）的表达，维持机体免疫稳态具有重要意义。已显示出大黄素对抗炎和免疫调节具有潜在作用。本研究旨在探讨大黄对烧伤脓毒症大鼠糖皮质激素受体表达及细胞免疫功能的影响。方法：66只健康雄性Sprague道利（SD）大鼠随机分为脓毒症组（n = 24）、大黄组（n = 24）和对照组（n = 18），每组再根据不同时间点随机分为12、24和72 h亚组。 在脓毒症模型建立时，大黄组大鼠经胃管给予50 mg/kg大黄粉溶于1 mL生理盐水中，脓毒症组和对照组给予生理盐水。采用放射配体结合法测定肝细胞胞浆GR结合活性和外周血白细胞GR结合量。采用流式细胞仪检测外周血淋巴细胞中CD 4+、CD 8+、CD 4 + CD 25 +T细胞、CD 19 +B细胞和自然杀伤（NK）细胞的百分比。为了评估组间差异，采用单因素方差分析（ANOVA）和Scheffe多重比较技术。每组内基于时间的测量之间的比较采用ANOVA重复测量进行。结果如下：脓毒症组肝胞液GR结合活性和外周血白细胞GR结合容量均呈时间依赖性下降（分别为t = 23.045，P < 0.01; t = 24.395，P < 0.05），大黄治疗后呈时间依赖性上升（分别为t = 19.965，P < 0.05; t = 17.140，P < 0.05）。脓毒症后12 h，脓毒症组外周血中CD 4 + T细胞百分比、CD 4 +/CD 25 + T细胞比率和CD 19 + B细胞显著增加（分别与对照组小鼠相比，t=-3.395，P <0.01; t = 2.568，P <0.05; t = 2.993，P <0.05）。 然而，在脓毒症组中，外周血中NK细胞的百分比显著降低（t =-2.022，P <0.05，与对照小鼠相比）。 脓毒症后12 h，脓毒症组外周血中CD 8 + T细胞百分比显著降低（t =-2.191，P <0.05，与对照组小鼠相比），大黄组显著升高（t = 2.953，P <0.05，与脓毒症小鼠相比）。 脓毒症后72 h，脓毒症组外周血CD 4 +/CD 25 + T细胞比值显著升高（t = 2.508，P <0.05），大黄组显著降低（t = 3.378，P <0.05）。 与脓毒症组相比，大黄组72 h时外周血CD 19 + B细胞百分比显著降低（t = 2.041，P <0.05）。 结论：RxD在脓毒症的发生发展过程中可能具有潜在的抗炎和免疫调节作用。
Background: It is important to modulate the expression of glucocorticoids receptor (GR) in tress and maintain the immunity homeostasis in sepsis process. Rhubarb have been shown to have potential effects on anti-inflammatory and immune modulation. The present study was designed to investigate the effects of rhubarb on the expression of GR and cellular immunity in burn-induced septic rats. Methods: Sixty-six healthy male Sprague Dawley (SD) rats were randomized into sepsis group (n = 24), rhubarb group (n = 24), and control group (n = 18); each group were further randomized into 12, 24, and 72 h subgroups according to different time points. During onset of the sepsis model, the rats in the rhubarb group were infused with 50 mg/kg rhubarb powder dissolved into 1 mL saline through gastric tube, while sepsis and control groups were treated with saline. The binding activity of GR in liver cytosol and binding capacity of GR in peripheral blood leucocyte were analyzed by radiation ligands binding assay. The percentages of CD4+,CD8+,CD4+CD25+T cells, CD19+B cells as well as natural killer (NK) cells in the lymphocytes in peripheral blood were detected by flow cytometer. For assessing the differences among groups, one-way analysis of variance (ANOVA) with Scheffe multi-comparison techniques were employed. Comparisons between time-based measurements within each group were performed with ANOVA repeated measurement. Results: The binding activity of GR in liver cytosol and binding capacity of GR in peripheral blood leucocyte were significantly decreased in a time-dependent manner in sepsis group (t = 23.045, P < 0.01; t = 24.395, P < 0.05, respectively), which were increased in a time-dependent manner after rhubarb administration (t = 19.965, P < 0.05; t = 17.140, P < 0.05, respectively). Twelve hours after sepsis, the percentages of CD4+ T cells, CD4+/CD25+ T cell ratio, and CD19+ B cells in the peripheral blood were significantly increased in the sepsis group (t = −3.395, P < 0.01; t = 2.568, P < 0.05; t = 2.993, P < 0.05, vs. control mice, respectively). However, the percentage of NK cells in the peripheral blood were significantly decreased in the sepsis group (t = −2.022, P < 0.05, vs. control mice). Twelve hours after sepsis, the percentage of CD8+ T cells were significantly decreased in the peripheral blood in the sepsis group (t = −2.191, P < 0.05, vs. control mice) and were significantly increased in the rhubarb group (t = 2.953, P < 0.05, vs. sepsis mice). Seventy-two hours after sepsis, the ratio of CD4+/CD25+ T cell in peripheral blood were significantly increased in the sepsis group (t = 2.508, P < 0.05, vs. control mice) while were significantly decreased in the rhubarb group (t = 3.378, P < 0.05, vs. control mice). Furthermore, the percentages of CD19+ B cell in peripheral blood were significantly decreased at 72 h in the rhubarb group (t = 2.041, P < 0.05 vs. sepsis group). Conclusions: Rhubarb might play potential anti-inflammatory and immunomodulatory roles in the sepsis processes.