Institute of Molecular Technology for Drug Discovery and Synthesis, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, People's Republic of China.
Menopause. 2010 Nov-Dec;17(6):1174-81. doi: 10.1097/gme.0b013e3181e39a2b.
The present study was designed to determine whether Fructus Ligustri Lucidi (FLL) ethanol extract can directly regulate vitamin D metabolism both in vivo and in vitro.
Eleven-month-old, aged Sprague-Dawley sham-operated and ovariectomized (OVX) female rats were fed a normal-calcium (Ca) diet (0.6% Ca, 0.65% phosphorus) and received either FLL (700 mg/kg) or vehicle daily for 12 weeks. The in vitro effects of FLL on vitamin D metabolism were studied using primary cultures of the rat renal proximal tubules. mRNA and protein expressions of 25-hydroxyvitamin D-1α hydroxylase (1-OHase) and vitamin D receptor (VDR) in the kidney and proximal tubule were measured using real-time polymerase chain reaction and Western blotting, respectively. The concentrations of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) synthesized by renal 1-OHase were measured by a competitive enzyme immunoassay.
FLL treatment significantly increased serum 1,25(OH)2D3 levels in both sham (P < 0.01) and OVX (P < 0.05) rats. FLL increased renal 1-OHase and VDR protein and mRNA expressions in sham rats. Protein expression of renal 1-OHase, but not VDR, was also up-regulated in OVX rats during FLL treatment. 1-OHase mRNA and 1-OHase activity were increased by FLL treatment in primary cultures of renal proximal tubule cells.
FLL could increase the circulating levels of 1,25(OH)2D3 in vivo in aged female rats by directly stimulating 1-OHase activity. Thus, it might be an ideal oral agent that can help to improve the ability to induce 1,25(OH)2D3 synthesis and Ca balance in postmenopausal women who are of high risk of developing osteoporosis.
本研究旨在确定女贞子乙醇提取物是否可以在体内和体外直接调节维生素 D 代谢。
11 月龄、老龄 Sprague-Dawley 假手术和去卵巢（OVX）雌性大鼠给予正常钙（Ca）饮食（0.6% Ca，0.65%磷），并每日给予女贞子（700 mg/kg）或载体 12 周。使用大鼠肾近端小管的原代培养物研究女贞子对维生素 D 代谢的体外影响。使用实时聚合酶链反应和 Western 印迹分别测量肾脏和近端小管中 25-羟维生素 D-1α羟化酶（1-OHase）和维生素 D 受体（VDR）的 mRNA 和蛋白表达。通过竞争性酶免疫测定测量肾 1-OHase 合成的 1,25-二羟维生素 D3（1,25（OH）2D3）的浓度。
女贞子治疗可显著增加假手术（P < 0.01）和 OVX （P < 0.05）大鼠的血清 1,25（OH）2D3 水平。女贞子增加了 sham 大鼠的肾 1-OHase 和 VDR 蛋白和 mRNA 表达。在 FLL 治疗期间，OVX 大鼠的肾 1-OHase 蛋白表达也上调，但 VDR 蛋白表达没有上调。女贞子治疗可增加原代培养的肾近端小管细胞中 1-OHase mRNA 和 1-OHase 活性。
女贞子可通过直接刺激 1-OHase 活性，增加老龄雌性大鼠体内 1,25（OH）2D3 的循环水平。因此，它可能是一种理想的口服药物，可以帮助提高患有骨质疏松症高风险的绝经后妇女诱导 1,25（OH）2D3 合成和 Ca 平衡的能力。
