麦冬地芍汤对NOD小鼠血清及颌下腺中VIP及Th1/Th2,Th17/Treg免疫平衡的影响

Effects of Maidong Dishao Decoction on VIP and Immune Balance of Th1/Th2,Th17/Treg in Serum and Submandibular Glands of NOD Mice with Sj?gren’s Syndrome

目的:观察麦冬地芍汤对干燥综合征模型(NOD)小鼠血清及颌下腺中血管活性肠肽(VIP)、γ-干扰素(IFN-γ)、白细胞介素-10(IL-10)、白细胞介素-17A(IL-17A)的表达及Th1/Th2,Th17/Treg免疫平衡的影响,探讨其作用机制。方法:33只雌性NOD小鼠随机分为模型组、羟氯喹组、中药组3组,8只美国癌症研究所(ICR)小鼠为空白组。适应性喂养1周后,羟氯喹组、中药组分别灌服羟氯喹溶液及麦冬地芍汤,空白组、模型组生理盐水灌胃。观察小鼠10、13、16周龄唾液流率的变化和18周龄时血清及颌下腺中VIP及细胞因子IFN-γ,IL-10,IL-17A的含量。对颌下腺进行HE染色,观察淋巴细胞浸润度。结果:与模型组相比,中药组小鼠16周龄时唾液流率明显改善(P<0.01),18周龄时血清及颌下腺中VIP浓度明显升高(P<0.05),Th1/Th2,Th17/Treg明显降低(P<0.01)。18周龄时,麦冬地芍汤组组织学评分低于模型组(P<0.05)。结论:麦冬地芍汤能显著改善NOD小鼠的干燥症状。机制可能与其上调VIP的表达,调节Th1/Th2,Th17/Treg免疫平衡相关。

Objectives:To observe the effect of Maidong Dishao Decoction(MDDSD) on the expression of vasoactive intestinal peptide(VIP),interferon-γ(IFN-γ),interleukin-10(IL-10),interleukin-17 A(IL-17 A) and immune balance of Th1/Th2,Th17/Treg in serum and submandibular glands(SMGs) of non-obese diabetic(NOD) mice with Sjogren’s syndrome(SS),and to explore its mechanisms. Methods:Thirty-three female NOD mice were randomly and equally divided into3 groups:the model group,the hydroxychloroquine(HCQ) group,and the MDDSD group. Eight Institute of Cancer Research(ICR) mice served as the normal group. After 1-week acclimation,the HCQ and MDDSD groups were intragastrically administered with HCQ and MDDSD respectively,and the normal and model groups were administered with normal saline. Changes in the salivary flow rate were observed.Mice from all 4 groups were sacrificed at the age of 18 weeks. The serum and SMGs were collected.Serum cytokines interferon-γ(IFN-γ),interleukin-10(IL-10),interleukin-17 A(IL-17 A) and vasoactive intestinal peptide(VIP) were detected by enzyme-linked immunosorbent assay. The SMGs were collected. Histological changes in the SMGs were examined by hematoxylin and eosin(HE) staining,the infiltration of lymphocytes was observed. Results:Compared with the model group,the salivary flow of the MDDSD group increased significantly(P<0.01),and the ratio of Th1/Th2,Th17/Treg was lower than that of the model group(P<0.01). Besides,the VIP was up-regulated in the MDDSD-treated mice(P<0.05),and histological score of the MDDSD group decreased significantly(P<0.05). Conclusions:MDDSD is beneficial in protecting structure of NOD mice. The mechanism may be associated with the correction of the Th1/Th2 and Th17/Treg cytokine imbalance,and with the prevention of a progressive decline of the VIP level.