益生菌Lactobacillus casei Shirota合併gamma-胺基丁酸對乾癬小鼠之影響

Abstract

乾癬為一種免疫失調所引發的皮膚發炎疾病，全球約有2-3 % 的人罹患此疾病。已知gamma-aminobutyric acid (GABA) 為抑制性神經傳遞物質，且具抗發炎作用。本研究室先前研究以imiquimod (IMQ) 誘發乾癬小鼠模式，分別測得補充GABA可降低小鼠皮膚IL-17量，改善皮膚表皮層增厚，以及補充代田菌Lactobacillus casei Shirota (LcS) 減少乾癬小鼠脾臟細胞IL-17分泌，降低小鼠皮膚IL-22、IL-6量，改善小鼠皮屑的產生。因此，本研究欲探討同時補充LcS和GABA是否能改善乾癬小鼠皮膚的病徵。實驗方法為將C57BL/6小鼠分為控制組 (Ctrl)、IMQ誘發組 (IMQ)、補充代田菌和GABA組 (LcS+GABA/IMQ)、及類固醇藥物dexamethasone的正控制組 (IMQ/Dex)。餵飼LcS+GABA/IMQ組小鼠含GABA的飼料並每天管餵LcS，4週後進行連續5天塗抹IMQ誘發乾癬，Ctrl組塗抹凡士林，於第6天犧牲取皮膚和脾臟等組織分析。結果顯示補充LcS和GABA組乾癬小鼠的皮膚紅斑及厚度和皮膚表皮層厚度顯著低於IMQ組，皮膚促發炎細胞激素IL-17、IL-22、TNF-α、IL-6、IL-1β、IFN-γ分泌量、脾臟IL-17分泌量顯著低於IMQ組。LcS+GABA/IMQ組MLN細胞TNF-α、IL-6分泌量顯著低於IMQ組。以上結果顯示，補充LcS及GABA能有效減緩乾癬皮膚病徵及改善發炎現象，具有減緩病情發展的潛力。

Psoriasis is a chronic autoimmune skin disorder that affects approximately 2-3% of the global population. Our previous study has shown that gamma-aminobutyric acid (GABA) and Lactobacillus casei Shirota (LcS) have immunomodulating effects. Therefore, this study aims to investigate whether supplementing with both GABA and LcS might have a more effective outcome on skin symptoms and inflammation in an imiquimod (IMQ)-induced psoriasis-like murine model. The experimental procedures were to divide C57BL/6 mice into a control group (Ctrl), an IMQ-induced group (IMQ), a combined LcS and GABA supplemented group (LcS+GABA/IMQ), and a dexamethasone (Dex)-treated positive control group (IMQ/Dex). The LcS+GABA/IMQ group fed a diet containing GABA and daily tube-feeding with LcS for 4 weeks before IMQ induction. Then, mice were treated with IMQ or vaseline (Ctrl) for 5 consecutive days, and all groups were sacrificed on the 6th day. The results demonstrated that the LcS+GABA/IMQ group showed significantly decreased erythema and skin thickness compared to the IMQ group in IMQ-induced psoriasis mice. Furthermore, the LcS+GABA/IMQ group showed significantly lower secretion of IL-17, IL-22, TNF-α, IL-6, IL-1β and IFN-γ in the skin and IL-17 in the spleen, compared to the IMQ group. Additionally, the LcS+GABA/IMQ group showed significantly lower secretion of TNF-α and IL-6 in MLN cells compared to the IMQ group. These results demonstrated that supplementation with LcS and GABA alleviated psoriatic-like skin symptoms and inflammation, suggesting its potential effect for alleviating the severity of psoriasis.