云南特色药物喙尾琵琶甲成骨与抗炎作用研究

Alveolar bone loss caused by periodontitis eventually leads to the loss of teeth. Osteoporosis patients are prone to fracture. Therefore, osteogenesis drugs are particularly important for the treatment of these two diseases. Due to the severe side effects and uncertain therapeutic effect of the commercialized drugs which promote bone formation, more researchers are turning to search for natural products for the prevention and treatment of diseases. In this study, 60 insect-origin drugs were isolated and screened in vitro. Four drugs with potential osteogenetic activity were found. Among these, three extracts from Blaps rynchopetera Fairmaire were selected. The osteogenesis activity and anti-inflammatory activity of Blaps rynchopetera Fairmaire extracts will be verified in rat experimental periodontitis model and mice osteoporosis model in vivo. The osteogenic and anti-inflammatory mechanisms of the extracts with distinct efficacy in vivo will be studied further in vitro. At the same time, the treatment relationship between periodontitis and osteoporosis will be explored. The new effective medicines for periodontitis and osteoporosis might be expected to be sought out from our study. More importantly, multiple drugs with osteogenesis and anti-inflammatory activity might be discovered by screening, which lays a foundation for the new drugs development possessed fully independent intellectual property rights.

牙周炎所致的牙槽骨缺损最终导致牙齿丧失，骨质疏松症患者容易发生骨折，临床上对治疗上述两种疾病的成骨药物的需求尤为迫切。目前商品化的药物如促进骨形成的产品由于严重的副作用和不确定的治疗效果，使更多的研究者转而寻找天然药物进行疾病的预防和治疗。我们的前期工作从云南地区昆虫中分离获得的60个虫源性药物中筛选出4个具有潜在体外成骨活性药物，其中3个为喙尾琵琶甲提取物。本课题拟进一步研究喙尾琵琶甲提取物对实验性牙周炎大鼠以及骨质疏松症小鼠的药效学作用，以验证喙尾琵琶甲提取物的体内成骨活性及抗炎效果。在体内实验验证有良好药效的药物将通过体外实验以阐明其成骨和抗炎机制，并探究牙周炎与骨质疏松症在药物治疗上的关系。本研究有望为临床治疗牙周炎、骨质疏松症患者提供新的有效药物。更为重要的是，预期本项目将可能筛选到多个具有成骨及抗炎活性的药物，为研发有完全自主知识产权的促成骨及抗炎新药奠定基础。

牙周炎和骨质疏松症都是以骨代谢平衡紊乱、骨吸收强于骨形成为特征。牙周炎所致的牙槽骨缺损最终导致牙齿丧失，骨质疏松症患者容易发生骨折。目前商品化的药物由于严重的副作用和不确定的治疗效果，使更多的研究者转而寻找天然药物。我们的前期工作从云南地区昆虫中分离获得的60个虫源性药物中筛选出4个具有潜在体外成骨活性药物，其中3个为喙尾琵琶甲来源（分别是喙尾琵琶甲总提取物，喙尾琵琶甲活性部位和单体B），同时也发现柚皮苷可促进小鼠类成骨细胞和骨髓间充质干细胞成骨相关基因的表达。本研究首先从喙尾琵琶甲虫体获得喙尾琵琶甲总提取物和活性部位，优化和制备了相应的口腔膜剂，建立大鼠实验性牙周炎模型，观察含药膜剂对炎症反应的抑制和对牙周组织缺损的再生效果。结果表明所制备的含药口腔膜剂能够初步满足实验性牙周炎大鼠药理药效实验的应用；对大鼠实验性牙周炎模型的牙周组织有一定的抗炎作用，并对缺损的牙周组织有一定的成骨作用。另一方面，对柚皮苷、雌激素和维生素D进行了生信分析，并采用去卵巢法建立绝经后骨质疏松症大鼠模型，探究喙尾琵琶甲总提取物和柚皮苷对骨质疏松症大鼠的药效学作用。结果显示，绝经后骨质疏松症大鼠给予柚皮苷后，血清碱性磷酸酶和尿液脱氧吡啶啉含量降低，血清雌二醇含量升高；骨密度、骨小梁体积分数、骨小梁厚度升高，其他骨微结构参数和股骨骨小梁显微结构明显改善，柚皮苷对绝经后骨质疏松症大鼠有成骨作用。喙尾琵琶甲总提取物及阳性对照雌二醇对绝经后骨质疏松症大鼠的药效作用未能显示，需进一步分析原因调整实验。单体B经结构鉴定为3, 4-二羟基苯乙酸，对其进行了生信分析，制备口腔膜剂，以探究单体B口腔膜剂对大鼠实验性牙周炎的药效作用，拟探究单体B对大鼠口腔菌群的影响及对牙周组织转录组的影响。研究为筛选具有成骨及抗炎活性的药物，为研发有完全自主知识产权的促成骨及抗炎新药奠定一定基础。