Abstract: OBJECTIVE: To investigate the influence of spleen deficiency on the epithelial barrier of jejunum and lungs in a rat model of spleen-deficiency and the effect and potential specialized pro-resolving mediators(SPMs) mechanism of chiropractic manipulation.METHODS: Three-week-old male Sprague-Dawley rats were divided randomly into normal control group(n = 6), spleen-deficiency group(n = 5) and chiropractic group(n = 6).Spleen-deficiency model was induced in spleen-deficiency group and chiropractic group.Moreover, chiropractic manipulation was performed in chiropractic group.Four weeks later, systemic Th1/Th2 balance was evaluated by the ratio of plasma interferon(IFN)-γ/interleukin(IL)-4 levels by enzyme-linked immunosorbent assay(ELISA).Epithelial barrier integrity were assessed by the observation of morphological changes by hematoxylin-eosin staining and zonula occludens(ZO)-1 gene expressions by quantitative real time polymerase chain reaction in jejunum and lungs.Plasma resolvin D1(RvD1) and lipoxin A4(LXA4) levels were measures by ELISA for endogenous SPMs production.The levels of docosahexaenoic acid(DHA) and arachidonic acid(AA) in jejunum and lungs were also measured by HPLC-MS/MS.RESULTS: Comparing with normal control group,spleen-deficiency group showed disrupted mucosa in jejunum, inflammatory condition in lungs, significantly decreased ratio of plasma IFN-γ/IL-4 levels and lower expressions of ZO-1 m RNA in both jejunum and lung tissues.Comparing with spleen-deficiency group, chiropractic group had less disrupted mucosa in jejunum and inflammatory condition in lungs, significantly increased systemic ratio of IFN-γ/IL-4 and expressions of ZO-1 m RNA in both jejunum and lung tissues.Chiropractic group had significantly enhanced plasma levels of RvD1 and LXA4, but had no significantly higher levels of DHA and AA in jejunum and lungs when comparing with spleen-deficiency group.CONCLUSION: Spleen deficiency caused systemic Th1/Th2 imbalance towards Th2 polarization and epithelial barrier disruption in jejunum and lungs.Chiropractic manipulation helped enhance endogenous SPMs production, which might be one of the action mechanism of chiropractic manipulation on the improvement of epithelial barrier disruption.

Key words: Manipulation,chiropractic, Th1-Th2 balance, Epithelial barrier, Specialized pro-resolving mediators, Spleen deficiency