用超溶性姜黄素/ turmeric 治疗的 MRL-lpr/lpr 小鼠的淋巴结病、唾液腺浸润和蛋白尿显著减少：用姜黄素治疗可提高生存率。
Significantly reduced lymphadenopathy, salivary gland infiltrates and proteinuria in MRL-lpr/lpr mice treated with ultrasoluble curcumin/turmeric: increased survival with curcumin treatment.
机构信息
Department of Medicine , University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma , USA ; Oklahoma Medical Research Foundation , Arthritis & Clinical Immunology Program , Oklahoma City, Oklahoma , USA ; Department Veterans Affairs Medical Center, Oklahoma City, Oklahoma, USA.
Department of Medicine , University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma , USA ; Oklahoma Medical Research Foundation , Arthritis & Clinical Immunology Program , Oklahoma City, Oklahoma , USA.
出版信息
Lupus Sci Med. 2015 Sep 8;2(1):e000114. doi: 10.1136/lupus-2015-000114. eCollection 2015.
OBJECTIVES
Commercial curcumin (CU), derived from food spice turmeric (TU), has been widely studied as a potential therapeutic for a variety of oncological and inflammatory conditions. Lack of solubility/bioavailability has hindered curcumin's therapeutic efficacy in human diseases. We have solubilised curcumin in water applying heat/pressure, obtaining up to 35-fold increase in solubility (ultrasoluble curcumin (UsC)). We hypothesised that UsC or ultrasoluble turmeric (UsT) will ameliorate systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS)-like disease in MRL-lpr/lpr mice.
METHODS
Eighteen female MRL-lpr/lpr (6 weeks old) and 18 female MRL-MpJ mice (6 weeks old) were used. Female MRL-lpr/lpr mice develop lupus-like disease at the 10th week and die at an average age of 17 weeks. MRL-MpJ mice develop lupus-like disease around 47 weeks and typically die at 73 weeks. Six mice of each strain received autoclaved water only (lpr-water or MpJ-water group), UsC (lpr-CU or MpJ-CU group) or UsT (lpr-TU or MpJ-TU group) in the water bottle.
RESULTS
UsC or UsT ameliorates SLE in the MRL-lpr/lpr mice by significantly reducing lymphoproliferation, proteinuria, lesions (tail) and autoantibodies. lpr-CU group had a 20% survival advantage over lpr-water group. However, lpr-TU group lived an average of 16 days shorter than lpr-water group due to complications unrelated to lupus-like illness. CU/TU treatment inhibited lymphadenopathy significantly compared with lpr-water group (p=0.03 and p=0.02, respectively) by induction of apoptosis. Average lymph node weights were 2606±1147, 742±331 and 385±68 mg, respectively, for lpr-water, lpr-CU and lpr-TU mice. Transferase dUTP nick end labelling assay showed that lymphocytes in lymph nodes of lpr-CU and lpr-TU mice underwent apoptosis. Significantly reduced cellular infiltration of the salivary glands in the lpr-TU group compared with the lpr-water group, and a trend towards reduced kidney damage was observed in the lpr-CU and lpr-TU groups.
CONCLUSIONS
These studies show that UsC/UsT could prove useful as a therapeutic intervention in SLE/SS.
目的
商业姜黄素（CU）源自食品香料姜黄（TU），已被广泛研究作为治疗多种肿瘤和炎症疾病的潜在药物。溶解度/生物利用度低阻碍了姜黄素在人类疾病中的治疗效果。我们通过施加热/压使姜黄素在水中溶解，获得了高达 35 倍的溶解度增加（超溶姜黄素（UsC））。我们假设 UsC 或超溶姜黄（UsT）将改善 MRL-lpr/lpr 小鼠的系统性红斑狼疮（SLE）和干燥综合征（SS）样疾病。
方法
使用 18 只雌性 MRL-lpr/lpr（6 周龄）和 18 只雌性 MRL-MpJ 小鼠（6 周龄）。10 周龄时，雌性 MRL-lpr/lpr 小鼠出现狼疮样疾病，并在平均 17 周时死亡。MRL-MpJ 小鼠在 47 周左右出现狼疮样疾病，通常在 73 周时死亡。每组各有 6 只小鼠分别接受高压灭菌水（lpr-water 或 MpJ-water 组）、UsC（lpr-CU 或 MpJ-CU 组）或 UsT（lpr-TU 或 MpJ-TU 组）治疗。
结果
UsC 或 UsT 通过显著减少淋巴细胞增殖、蛋白尿、病变（尾巴）和自身抗体，改善 MRL-lpr/lpr 小鼠的 SLE。lpr-CU 组比 lpr-water 组的存活率提高了 20%。然而，lpr-TU 组的平均寿命比 lpr-water 组短 16 天，这是由于与狼疮样疾病无关的并发症所致。与 lpr-water 组相比，CU/TU 治疗通过诱导细胞凋亡显著抑制了淋巴结肿大（p=0.03 和 p=0.02）。lpr-water、lpr-CU 和 lpr-TU 小鼠的淋巴结重量分别为 2606±1147、742±331 和 385±68mg。末端转移酶 dUTP 缺口末端标记（TUNEL）检测显示，lpr-CU 和 lpr-TU 小鼠的淋巴结中的淋巴细胞发生了凋亡。与 lpr-water 组相比，lpr-TU 组的唾液腺细胞浸润明显减少，lpr-CU 和 lpr-TU 组的肾脏损伤有减少的趋势。
结论
这些研究表明，UsC/UsT 可能作为治疗 SLE/SS 的一种治疗干预措施很有用。
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