Cheng F L, Qi X P, Zhao C Q, An Y F, Ren J J, Li C
Department of Otorhinolaryngology Head and Neck Surgery, Shanxi Medical University affiliated Second Hospital, Taiyuan 030001, China.
Department of Otorhinolaryngology Head and Neck Surgery, Ningbo City Medical Treatment Center Lihuili Hospital, Ningbo 315041, China.
Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2018 Oct 7;53(10):757-764. doi: 10.3760/cma.j.issn.1673-0860.2018.10.008.
To study the effect of dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis on the pathogenesis of allergic rhinitis (AR) by the mouse model of decreased endogenous glucocorticoid (GC) after adrenalectomy, and further explore the mechanism of neural-endocrine regulation. According to literatures, adrenalectomized (ADX) mice and AR model were established. Eighty mice were randomly divided into four groups (=20 per group) including control group, AR group of normal mice (AR group), AR group of bilateral ADX (bilateral ADX/AR group) and AR group of unilateral ADX (unilateral ADX/AR group). In order to assess the model of ADX, adrenal gland tissue was assayed by HE staining and the plasma adrenocorticotropic hormone (ACTH) and cortisol (CORT) concentrations were measured by enzyme-linked immunosorbent assay (ELISA). The behavioral observation, OVA-sIgE assessments and count of eosinophils/mast cells by the HE/Toluidine Blue staining of nasal septum mucosa tissue were performed to evaluate the AR model. The expression of peripheral blood CD4(+) IL4(+) T cells (Th2 cells) and CD4(+) IFN-γ(+) T cells (Th1 cells), splenocytes of CD4(+) CD25(+) Treg cells (Treg cells) were measured by flow cytometry to study the influence of endogenous GC on immunological indexes in different groups of mice. SPSS 16.0 software was used to analyze the data. The concentrations of OVA-sIgE in control group, AR group, bilateral ADX/AR group and unilateral ADX/AR group mice were (28.86±3.62) ng/ml, (76.27±16.47) ng/ml, (48.37±8.89) ng/ml, (49.86±7.19) ng/ml, respectively. There was statistically significant difference between control group and AR group (=7.09, <0.05), AR group and bilateral ADX/AR group (=4.81, <0.05), AR group and unilateral ADX/AR group (=5.21, <0.05). The level of Th2 cells in different four groups were (0.71±0.24)%, (7.03±1.95)%, (2.44±2.06)%, (3.20±1.21)%, respectively. There was statistically significant difference between control group and AR group (=-2.93, <0.05), AR group and bilateral ADX/AR group (=-4.67, <0.05), AR group and unilateral ADX/AR group (=-3.61, <0.05). The expression of Th2 in bilateral ADX/AR group is lower than that in unilateral ADX/AR group without significant difference (=4.39, >0.05). Meanwhile, the level of Th1 cells in different four groups was (0.58±0.76)%, (0.57±0.59)%, (0.72±0.34)%, (1.03±0.32)%, respectively, with no significant difference among these groups. The proportion of Treg cells was (11.10±2.18)%, (4.10±1.07)%, (7.15±0.92)%, (4.58±1.05)%, respectively, with significant difference between control and other groups ( value was -7.171, -8.273, -8.360, respectively, all <0.05). Compared with AR group, Treg cells increased significantly in bilateral ADX/AR group (=-2.607, <0.05). In addition, lower expression of eosinophil and mast cell were detected in the local nasal tissue of bilateral ADX/AR group, and mast cell degranulation wasn't be observed. Unilateral or bilateral ADX leads to HPA axis dysfunction and endogenous GC deprivation, possibly regulating the mechanism of AR through Th1/Th2 immune bias and Tregs cell' activity.
通过肾上腺切除术后内源性糖皮质激素（GC）降低的小鼠模型，研究下丘脑 - 垂体 - 肾上腺（HPA）轴功能障碍对变应性鼻炎（AR）发病机制的影响，并进一步探讨神经 - 内分泌调节机制。根据文献，建立肾上腺切除（ADX）小鼠和AR模型。80只小鼠随机分为四组（每组n = 20），包括对照组、正常小鼠AR组（AR组）、双侧ADX的AR组（双侧ADX/AR组）和单侧ADX的AR组（单侧ADX/AR组）。为评估ADX模型，采用HE染色检测肾上腺组织，并通过酶联免疫吸附测定（ELISA）测量血浆促肾上腺皮质激素（ACTH）和皮质醇（CORT）浓度。通过行为观察、OVA - sIgE评估以及鼻中隔黏膜组织的HE/甲苯胺蓝染色对嗜酸性粒细胞/肥大细胞计数来评估AR模型。采用流式细胞术检测外周血CD4(+)IL4(+)T细胞（Th2细胞）、CD4(+)IFN - γ(+)T细胞（Th1细胞）以及脾细胞中CD4(+)CD25(+)调节性T细胞（Treg细胞）的表达，以研究内源性GC对不同组小鼠免疫指标的影响。使用SPSS 16.0软件分析数据。对照组、AR组、双侧ADX/AR组和单侧ADX/AR组小鼠的OVA - sIgE浓度分别为(28.86±3.62) ng/ml、(76.27±16.47) ng/ml、(48.37±8.89) ng/ml、(49.86±7.19) ng/ml。对照组与AR组之间差异有统计学意义（t = 7.09，P < 0.05），AR组与双侧ADX/AR组之间差异有统计学意义（t = 4.81，P < 0.05），AR组与单侧ADX/AR组之间差异有统计学意义（t = 5.21，P < 0.05）。四组中Th2细胞水平分别为(0.71±0.24)%、(7.03±1.95)%、(2.44±2.06)%、(3.20±1.21)%。对照组与AR组之间差异有统计学意义（t = - 2.93，P < 0.05），AR组与双侧ADX/AR组之间差异有统计学意义（t = - 4.67，P < 0.05），AR组与单侧ADX/AR组之间差异有统计学意义（t = - 3.61，P < 0.05）。双侧ADX/AR组中Th2的表达低于单侧ADX/AR组，但差异无统计学意义（t = 4.39，P > 0.05）。同时，四组中Th1细胞水平分别为(0.58±0.76)%、(0.57±0.59)%、(0.72±0.34)%、(1.03±0.32)%，各组之间差异无统计学意义。Treg细胞比例分别为(11.10±2.18)%、(4.10±1.07)%、(7.15±0.92)%、(4.58±1.05)%，对照组与其他组之间差异有统计学意义（t值分别为 - 7.171、 - 8.273、 - 8.360，均P < 0.05）。与AR组相比，双侧ADX/AR组中Treg细胞显著增加（t = - 2.607，P < 0.05）。此外，在双侧ADX/AR组的局部鼻组织中检测到嗜酸性粒细胞和肥大细胞的表达较低，且未观察到肥大细胞脱颗粒现象。单侧或双侧ADX导致HPA轴功能障碍和内源性GC缺乏，可能通过Th1/Th2免疫偏移和Tregs细胞活性调节AR的发病机制。
