Fan Jing-Zheng, Wang Yi, Meng Yan, Li Guan-Wu, Chang Shi-Xin, Nian Hua, Liang Yong-Jie
1Department of Respiratory Medicine, East Hospital, Tongji University School of Medicine, Shanghai, China 2Department of Gastroenterology, Yueyang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China 3Department of Radiology, Yueyang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China 4Department of Pharmacy, Yueyang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Menopause. 2015 Dec;22(12):1343-50. doi: 10.1097/GME.0000000000000471.
Previous data have suggested that Panax notoginseng saponins (PNS) can prevent estrogen deficiency-induced bone loss by dual action: stimulation of new bone formation and inhibition of bone resorption. Marrow adipogenesis has been identified as a negative indicator of skeletal strength and integrity. This study assessed the effects of early PNS supplementation on bone microarchitecture preservation and marrow fat content in an ovariectomized rat model.
Forty adult female Sprague-Dawley rats were randomly assigned to four equal groups for 12 weeks of treatment: (1) sham operation (SHAM) + vehicle; (2) ovariectomy (OVX) + vehicle; (3) OVX + 17β-estradiol (25 μg/kg); (4) OVX + PNS (300 mg/kg/d, PO). Marrow fat content of the femur was determined, using fat/water magnetic resonance imaging (MRI), at baseline and 6 and 12 weeks after operation. At the end of the experiment, bone turnover, trabecular microarchitecture, and marrow adipocytes were assessed by serum biomarkers, micro-computed tomography (micro-CT), and histopathology, respectively. The effects of PNS on adipocytic differentiation were reflected by expression levels of the adipogenic genes PPARγ2 and C/EBPα, as determined by reverse transcription-polymerase chain reaction.
Ovariectomized rats experienced remarkable increases in marrow fat content across time points, which were accompanied by elevated rate of bone turnover, global volumetric bone density, and trabecular microarchitecture deterioration. These OVX-induced pathological changes are reversible in that most of them could be mostly corrected upon 17β-estradiol treatment. PNS treatment significantly reduced marrow adipogenesis (adipocyte density, -27.2%; size, -22.7%; adipocyte volume-to-tissue volume ratio, -53.3%; all P < 0.01) and adipocyte marker gene expression, and prevented bone mass loss and microarchitecture deterioration. Moreover, PNS enhanced osteoblast activity but suppressed osteoclast turnover, as evidenced by decreased levels of serum C-terminal telopeptides of type I collagen and elevated levels of alkaline phosphatase.
PNS mitigates estrogen deficiency-induced deterioration of trabecular microarchitecture and suppresses marrow adipogenesis.
先前的数据表明，三七总皂苷（PNS）可通过双重作用预防雌激素缺乏引起的骨质流失：刺激新骨形成和抑制骨吸收。骨髓脂肪生成已被确定为骨骼强度和完整性的负面指标。本研究评估了早期补充PNS对去卵巢大鼠模型骨微结构保存和骨髓脂肪含量的影响。
将40只成年雌性Sprague-Dawley大鼠随机分为四组，每组数量相等，进行为期12周的治疗：（1）假手术（SHAM）+赋形剂；（2）去卵巢（OVX）+赋形剂；（3）OVX+17β-雌二醇（25μg/kg）；（4）OVX+PNS（300mg/kg/d，口服）。在基线以及术后6周和12周时，使用脂肪/水磁共振成像（MRI）测定股骨的骨髓脂肪含量。实验结束时，分别通过血清生物标志物、显微计算机断层扫描（micro-CT）和组织病理学评估骨转换、小梁微结构和骨髓脂肪细胞。通过逆转录-聚合酶链反应测定成脂基因PPARγ2和C/EBPα的表达水平，以反映PNS对脂肪细胞分化的影响。
去卵巢大鼠在各个时间点的骨髓脂肪含量均显著增加，同时伴有骨转换率升高、整体体积骨密度增加和小梁微结构恶化。这些OVX诱导的病理变化是可逆的，因为在17β-雌二醇治疗后，大多数变化可以得到纠正。PNS治疗显著降低了骨髓脂肪生成（脂肪细胞密度，-27.2%；大小，-22.7%；脂肪细胞体积与组织体积比，-53.3%；所有P<0.01）和成脂标记基因表达，并防止了骨量流失和微结构恶化。此外，PNS增强了成骨细胞活性，但抑制了破骨细胞转换，这通过血清I型胶原C末端肽水平降低和碱性磷酸酶水平升高得以证明。
PNS减轻了雌激素缺乏引起的小梁微结构恶化，并抑制了骨髓脂肪生成。
