Kong Lingwen, Wu Jinfeng, Lin Yanhua, Wang Genfa, Wang Jia, Liu Jiaqi, Chen Meixia, Du Xin, Sun Jing, Lin Jinpei, Dong Jingcheng
Department of integrated traditional Chinese and western medicine, Huashan Hospital, Fudan University, Shanghai, PR China; Institute of integrated traditional Chinese and western medicine of Fudan University, Shanghai, PR China.
PLoS One. 2015 Feb 6;10(2):e0116427. doi: 10.1371/journal.pone.0116427. eCollection 2015.
Dysfunction of central and skin Hypothalamic-Pituitary-Adrenal (HPA) axis play important roles in pathogenesis of atopic dermatitis (AD). Our previous studies showed that several Chinese herbs could improve HPA axis function. In this study, we evaluated the anti-inflammatory effects of BuShenYiQi granule (BSYQ), a Chinese herbs formula, in AD mice and explored the effective mechanism from regulation of HPA axis.
The ovalbumin (OVA) induced AD mice model were established and treated with BSYQ. We evaluated dermatitis score and histology analysis of dorsal skin lesions, meanwhile, serum corticosterone (CORT), adrenocorticotropic hormone (ACTH), corticotropin-releasing hormone (CRH) and inflammatory cytokines were determined by ELISA. The changes of CRH/proopiomelanocortin(POMC) axis elements, corresponding functional receptors and crucial genes of glucocorticosteroidogenesis in the skin were measured by quantitative real-time PCR and western blot, respectively.
The symptoms and pathological changes in skin of AD mice were significantly improved and several markers of inflammation and allergy descended obviously after BSYQ treatment. We found that AD mice had insufficient central HPA tone, but these conditions were markedly improved after BSYQ treatment. The AD mice also showed a disturbed expression of skin HPA. In lesion skin of AD mice, the mRNA and protein expressions of CRH decreased significantly, on the contrary, POMC and cytochrome P450 side-chain cleavage enzyme (CYP11A1) increased markedly, meanwhile, NR3C1 (mouse GR), CRHR2 and 11-hydroxylase type 1(CYP11B1) were reduced locally. Most of these tested indexes were improved after BSYQ treatment.
AD mice displayed the differential expression pattern of central and skin HPA axis and BSYQ treatment significantly alleviated the symptoms of AD mice and presented anti-inflammatory and anti-allergic effects via regulating the expression of central and skin HPA axis.
中枢和皮肤下丘脑-垂体-肾上腺（HPA）轴功能障碍在特应性皮炎（AD）的发病机制中起重要作用。我们之前的研究表明，几种中药可以改善HPA轴功能。在本研究中，我们评估了中药配方补肾益气颗粒（BSYQ）对AD小鼠的抗炎作用，并从HPA轴调节方面探讨其作用机制。
建立卵清蛋白（OVA）诱导的AD小鼠模型并用BSYQ进行治疗。我们评估了背部皮肤损伤的皮炎评分和组织学分析，同时通过酶联免疫吸附测定法（ELISA）测定血清皮质酮（CORT）、促肾上腺皮质激素（ACTH）、促肾上腺皮质激素释放激素（CRH）和炎性细胞因子。分别通过定量实时聚合酶链反应（qRT-PCR）和蛋白质免疫印迹法检测皮肤中CRH/阿黑皮素原（POMC）轴元件、相应功能受体及糖皮质激素合成关键基因的变化。
BSYQ治疗后，AD小鼠皮肤的症状和病理变化得到显著改善，炎症和过敏的几个指标明显下降。我们发现AD小鼠中枢HPA张力不足，但BSYQ治疗后这些情况得到明显改善。AD小鼠还表现出皮肤HPA表达紊乱。在AD小鼠的皮损中，CRH的mRNA和蛋白表达显著降低，相反，POMC和细胞色素P450侧链裂解酶（CYP11A1）显著增加，同时，局部NR3C1（小鼠糖皮质激素受体）、CRHR2和11-β-羟化酶1（CYP11B1）减少。BSYQ治疗后，这些检测指标大多得到改善。
AD小鼠表现出中枢和皮肤HPA轴的差异表达模式，BSYQ治疗显著减轻了AD小鼠的症状，并通过调节中枢和皮肤HPA轴的表达呈现抗炎和抗过敏作用。
