【作者】 师彬；

【导师】 李刚；

【作者基本信息】 天津大学 ， 生物医学工程， 2009， 博士

【摘要】 [工作目的]研制一种创新型治疗股骨头坏死(Avascular Necrisis of the Femoral Head, ANFH)的新药-仙鹿活骨丸,并从细胞学角度探索其治疗股骨头坏死的机制。[研究方法]在本研究中,我们在临床经验方的基础上制成了治疗股骨头坏死的有效方剂-仙鹿活骨丸,其处方提出了益肾健骨、活血化瘀、通经活络止痛治疗股骨头坏死的新思路及重用动物类药的用药方法。处方将虫类药制成破壁微粉,植物药进行有效成分提取成浓缩剂,混合制成水丸。使用维甲酸型和激素型大鼠股骨头坏死两种最新的动物模型,从细胞水平上对仙鹿活骨丸激活成骨细胞功能、减少成骨细胞凋亡机制进行探讨。[研究结果]仙鹿活骨丸可以有效改善维甲酸所致股骨头缺血后骨密度降低,增强股骨头和股骨窝部位的骨密度水平,在微观的组织学方面,能够改善软骨表面凹陷,降低骨细胞变性坏死度;仙鹿活骨丸还可明显改善注射醋酸强的松龙后股骨头坏死大鼠体重下降等症状,改善血流变指标,增加HOM /HOP比值,流氏细胞仪检测和电镜观察表明其可以有效改善激素引起的骨细胞坏死。对大鼠成骨细胞(OB)进行分离和培养,MTT比色实验表明仙鹿活骨丸可以提高OB的增值能力,增强ALP表达,促进OB由G0/G1期进入S期,促进OB有丝分裂,促进成骨细胞再生。基因检测提示仙鹿活骨丸可以抑制OB凋亡过程中Bcl-2表达的下降及Bax表达的上升,从而抑制OB凋亡,阻止股骨头坏死恶化。急性毒性和长期毒性实验结果表明仙鹿活骨丸低毒、安全,可以在临床上使用。[研究结论]仙鹿活骨丸作为一种新药,成本低、副作用小、能够长期服用。其制备工艺先进,对激素型和维甲酸型大鼠股骨头坏死有较好治疗作用,还可以有效保护成骨细胞功能,治疗股骨头坏死,值得推广和应用。更多还原

【Abstract】 [PURPOSE] To develope a new creative drug to treat ANFH (Avascular Necrisis of the Femoral Head) named Xianlu Huogu Wan, and to study the treatment mechanism of Xianlu Huogu Wan on ANFH.[METHOD] In this study, we made a curative prescription of ANFH named Xianlu Huogu Wan. The prescription has some innovations on treatment of ANFH by tonifying kidney and healthy bone, promoting blood to dissolve the stasis, promotion and activating collaterals to relieve pain. We broke the insects drugs to worm powder drugs, extracted herbal for the active ingredients to concentrated dose and mix into water-paste pill. we used two types of animal model in rats, retinoic acid-caused and corticosteroid-caused type, and studied the activate function on osteoblast and reduction of osteoblast apoptosis on the cellular level.[RESULT] Xianlu Huogu Wan can improve reduction of the bone mineral density effectively after the lack of blood of femoral head due to retinoic acid induced and enhance the level of bone mineral density of the femoral head and femoral fossa. It can improve the cartilage surface of depression and reduce the degrees of cell degeneration and necrosis of cartilage. It can improve symptoms significantly, such as weight loss of the ANFH rats injected prednisolone acetate, improve blood flow targets, increase the HOM/HOP ratio and improve the bone necrosis caused by hormone by cell flow cytometry and electron microscopy. We isolate and culture the rat osteoblasts (OB), MTT colorimetric cents experiments show that it can increase the generation capabilities of OB and enhanced ALP expression, it can promote OB from G0/G1 phase to S phase, thus contributing to OB mitosis to promote osteoblast proliferation. Genetic tests show that Xianlu Huogu Wan can inhibit the decreased expression of Bcl-2 and increase expression of Bax in the process of OB apoptosis, thereby inhibit the OB necrosis to treat ANFH. The acute toxicity and long-term toxicity test results show that it has low toxicity to be used in clinical practice.[CONCLUSION] As a new medicine of low cost and low side effect, Xianlu Huogu Wan can be used to treat ANFH for long-term. Due to the advanced preparation, good therapeutic effect on hormone-caused and retinoic acid-caused ANFH on rat and the effective protection of osteoblast function in treatment of ANFH, it is worthy to popularize and apply.更多还原