Osteoporosis is a systemic bone disease characterized by decreased bone mass and deterioration of bone microstructure, which leads to increased bone fragility and increased risk of fractures. Casein kinase 2 interacting protein 1 (CKIP-1, also known as PLEKHO1) is involved in the biological process of bone formation, differentiation and apoptosis, and is a negative regulator of bone formation. QiangGuYin (QGY) is a famous TCM formula that has been widely used in China for the clinical treatment of postmenopausal osteoporosis for decades, but the effect in regulating CKIP-1 on osteoporosis is not fully understood. This study aimed to explore the potential mechanism of CKIP-1 participating in autophagy in bone cells through the AKT/mTOR signaling pathway and the regulatory effect of QGY. The results in vivo showed that QGY treatment can significantly improve the bone quality of osteoporotic rats, down-regulate the expression of CKIP-1, LC3II/I and RANKL, and up-regulated the expression of p62, p-AKT/AKT, p-mTOR/mTOR, RUNX2 and OPG. It is worth noting that the results in vitro confirmed that CKIP-1 interacts with AKT. By up-regulating the expression of Atg5 and down-regulating the p62, the level of LC3 (autophagosome) is increased, and the cells osteogenesis and differentiation are inhibited. QGY inhibits the combination of CKIP-1 and AKT in osteoblasts, activates the AKT/mTOR signaling pathway, inhibits autophagy, and promotes cell differentiation, thereby exerting an anti-osteoporosis effect. Therefore, QGY targeting CKIP-1 to regulate the AKT/mTOR-autophagy signaling pathway may represent a promising drug candidate for the treatment of osteoporosis.
目的 借助系统网络药理学及分子对接技术分析青娥丸治疗绝经后骨质疏松症的血清移行成分的机制.方法 通过中国知网、万方、维普、Pubmed等平台查阅文献,选取已经过实验研究验证的青娥丸组分中的入药血清成分作为研究对象.通过靶点预测数据库预测成分分子可能的作用靶点;应用GeneCard、Drugbank等疾病数据库检索疾病基因,应用venny2.1映射获取交集基因,应用STRING数据库、Cytoscape_v3.8.0软件中的Cyto NCA插件筛选核心基因并绘制蛋白质-蛋白质相互作用网络,使用Cytoscape_v3.8.0软件绘制中药-化合物-靶点-疾病网络,应用R语言和Clue go插件进行基因本体论分析、KEGG通路富集分析,应用AutoDock Tools 1.5.6和Discovery Studio 2020软件做分子对接分析.结果 共9种入血成分,81个交集基因,25个核心靶点,涉及137个生物过程、可能通过HIF-1 signaling pathway、AGE-RAGE signaling pathway in diabetic complications等41条通路治疗骨质疏松,分子对接显示关键血清成分与核心靶点具有较强的亲和力,结合性较好.结论 青娥丸中九种入血成分可能是治疗绝经后骨质疏松症的主要物质基础,为深入阐明该复方的作用机制提供一定依据.
Objective: To explore the effects of a TCM compound QiangGuYin (QGY) regulating osteoclast derived exosomal miRNAs on the Wnt/β-catenin pathway in osteoclast and osteoblasts. Methods: QGY containing serum was prepared to construct osteogenic and osteoclastic differentiation models. Setting up a non-medicated and a medicated serum group with intervention on osteoclast differentiation after extraction of exosomes, the exosome morphology, quantity as well as secretion were examined, while miRNA sequencing of exosomes from the groups was performed. Then, observing the expression of Runx2, OPN, OCN by qRT-PCR and Western blot after adding the groups of exosomes. Finally, RAW264.7 and BM-MSCs were intervened with medicated serum to observe different effects on the expression of β-catenin. Results: The morphology, quantity and secretion of exosomes were not affected by the presence of medicated versus non medicated serum, and exosomes from the two groups appeared identical by electron microscopy; the expression of Runx2, OPN, OCN, β-catenin and miR-27b-3p were markedly increased in osteoblast after intervening by medicated-serum exosomes. Conclusion: QGY can inhibit osteoclast differentiation and decrease the inhibitory effect of exosomes on osteoblast differentiation, and the mechanism may be through affecting miR-27b-3p in exosomes and interfering with the Wnt/β-catenin pathway, affecting osteoblast differentiation.
介绍史晓林教授治疗原发性骨质疏松症的临床经验.史晓林教授认为,原发性骨质疏松症属中医骨痿范畴.存在多虚多瘀、因虚致瘀的病机特点,治用益气温经法,即在补益肝、脾、肾三脏的基础上,加用温经通络、活血止痛的药物,既益脾肾以补一身之气,又温诸经以活血通络,标本兼治.以经验方强骨饮随症治疗,且注重生活起居及锻炼的调护.
糖皮质激素性骨质疏松症是一种由于应用糖皮质激素时间过长所导致的继发性骨质疏松症,可归属于中医学"骨痿"范围.从"壮火食气"探讨糖皮质激素性骨质疏松症的病机,认为糖皮质激素属"壮火"范畴,应用时间过长将食气伤阴,致使机体气阴两虚,气虚阴亏则血瘀,虚瘀甚者则生毒,火、虚、瘀、毒彼此交织,共发为骨痿.
[目的]观察自拟中药处方强骨饮对肾虚血瘀型绝经后骨质疏松(PMOP)患者下肢肌力、平衡及步态等多项指标的变化,评价强骨饮对患者跌倒风险因素的影响.[方法]将100例肾虚血瘀型PMOP患者随机分为试验组和对照组,每组各50例.对照组给予骨化三醇胶丸联合碳酸钙D3片治疗,试验组在对照组的基础上加用自拟中药处方强骨饮治疗,疗程为6个月.观察2组患者治疗前、治疗3个月和治疗6个月后的腰椎骨密度T值、髋关节肌群及膝关节肌群肌力、Tinetti平衡及步态量表评分和血钙水平的变化情况.[结果](1)观察过程中,试验组和对照组分别有6例和4例患者脱落,最终共有90例患者完成试验,其中试验组44例,对照组46例.(2)治疗3个月后,2组患者的腰椎骨密度T值均无明显变化(P>0.05);治疗6个月后,2组患者的腰椎骨密度T值均较治疗前提高(P<0.05),但治疗后组间比较,差异均无统计学意义(P>0.05).(3)治疗3个月后,试验组髋关节伸肌群和膝关节伸肌群肌力均较治疗前明显改善(P<0.05),而对照组仅髋关节伸肌群肌力明显改善(P<0.05);治疗6个月后,2组患者的髋关节伸肌群和膝关节伸肌群肌力均明显改善(P<0.05或P<0.01);组间比较,试验组在治疗6个月后对髋关节伸肌群和膝关节伸肌群肌力的改善作用均明显优于对照组(P<0.05).(4)治疗3个月后,试验组Tinetti平衡与步态评分较治疗前提高(P<0.01),而对照组无明显变化(P>0.05);治疗6个月后,2组患者的Tinetti平衡与步态评分均较治疗前提高(P<0.05或P<0.01);组间比较,试验组在治疗3个月和治疗6个月后对Tinetti平衡与步态评分的提高作用均明显优于对照组(P<0.05).(5)在经过3个月及6个月治疗后,2组患者的血钙水平均较治疗前有所提高(P<0.05或P<0.01),但组间比较差异均无统计学意义(P>0.05).[结论]强骨饮治疗肾虚血瘀型PMOP患者疗效确切,可有效提高患者下肢肌力,稳定患者步态,提高患者平衡能力,对预防患者跌倒有积极作用,可明显降低患者的跌倒风险.
糖皮质激素诱导性骨质疏松症(glucocorticoid-induced osteoporosis,GIOP)现已在临床上被逐步重视.从中医角度看,根据《黄帝内经》中"壮火食气"的理论,该疾病的主要发病机制为过用具有温热、刚烈性质的糖皮质激素,使人体的脏腑、气血、阴阳受损,不能濡养筋骨,骨失濡养则发为骨质疏松症.笔者对GIOP的病因病机进行了探讨,从"少火生气"理论出发,讨论了GIOP的治则与分期辨证论治,为临床认识和治疗GIOP提供新的思路.
骨质疏松症是老年人常见病,目前相关研究证实骨质疏松症与免疫系统之间存在联系,骨保护素(osteoprotegrin,OPG)/核因子κB受体活化因子配体(receptor activator of nuclear factor-κB ligand,RANKL)/核因子κB受体活化因子(receptor activator of nuclear factor-κB,RANK)信号通路是连接二者的关键通路.补体系统是重要的免疫系统,补体成分3在补体系统中占据重要地位.研究表明,补体成分3与骨质疏松症之间存在密切关系.开展补体成分3及其他免疫系统成分与骨质疏松症关系的研究,有助于为骨质疏松症的诊治提供新的方向.本文简要概述了补体系统,分析了OPG/RANKL/RANK信号通路在骨质疏松症发生发展中的作用机制,就补体成分3及其他免疫系统成分与骨质疏松症的关系的研究进展进行了综述.
绝经后骨质疏松症是老年女性常见疾病,属于中医学"骨痿"范畴,与肾虚、脾虚、血瘀有关,肾虚和脾虚是根本、血瘀是关键,且虚和瘀常相互作用;可采用益气温经法治疗该病,从而达到益气补肾、温经通络、活血化瘀的目的.本文对绝经后骨质疏松症的病因病机进行了探讨,并在此基础上对益气温经法治疗该病的理论基础及研究进展进行了阐述.
原发性骨质疏松症是一种常见的慢性病,病发往往悄无声息,多数患者并发骨折后才能发觉.随着中医药近几十年的发展,有关防治原发性骨质疏松症的中医临床研究日趋丰富,为中医药抗骨质疏松症的疗效提供了有力证据,在内治法和外治法两个方面均取得了显著的疗效.中医外治法[1]具有见效快,副反应小等特点,且历史悠久,使用方便.本文所讨论的穴位敷贴法属于中医外治法的一种类型,随着穴位贴敷运用的发展,目前在临床上出现了各种制剂,如透皮吸收贴剂、透皮控释制剂等,其药物有效成分吸收率更高,疗效更佳,广泛运用于内科疾病如哮喘、便秘和失眠等,在防治骨质疏松方面同样具有较好的疗效,但在临床上得不到较高的重视,临床研究报道相对较少,本文参考近5年文献从中医理论出发对穴位敷贴防治骨质疏松症的机制、选穴和临床运用等方面进行归纳和总结.旨在方便为各位学者提供穴位敷贴防治方法的最新研究状况,提升对穴位敷贴法的认识,使之在临床上得到更好的运用.
腰背疼痛是绝经后及老年性骨质疏松症的常见症状,常用的西医及中医疗法均存在一些不足之处.穴位贴敷疗法是基于中医基础理论及经络腧穴学说,通过辨证选取不同的药物和穴位,将药物制成贴膏贴敷于穴位,利用药物和穴位的双重作用从整体治疗疾病的方法,具有作用精准、不良反应少、操作简便等优点,已被用于绝经后及老年性骨质疏松症腰背疼痛的治疗,并取得了良好的疗效.本文概述了穴位贴敷疗法,对穴位贴敷疗法治疗绝经后及老年性骨质疏松症腰背疼痛的药物及穴位选择方面的研究进展进行了综述.
单纯性鼻出血属中医学"鼻衄"范畴,多因肺、肾、肝火旺盛,迫血妄行,血溢于清道:或气机逆乱挟热上窜鼻窍;少数因肾精亏虚或者气虚不摄所致."5·12"汶川大地震后,2008年5月16日至21日,笔者有幸跟随张成大教授前往绵阳九州体育馆为灾区人民义诊.期间,我们采用针刺尺泽为主穴的方法治疗单纯性鼻出血62例,现报告如下.
中风后肢体出现痉挛是中风的常见并发症之一,严重影响患者的预后及生存质量。本文综述了近十几年来针灸治疗中风后肢体痉挛状态的研究进展,旨在探讨针灸治疗中风后肢体痉挛状态的临床疗效及其研究机制,并包含笔者对中风后肢体痉挛状态的初步认识。
查阅近20年来关于阴虚证动物模型建立方法的文献,根据其在造模时的指导思想和具体方法,将其归纳为中医和西医理论指导两大类;从中医阴虚的病因、病机和证候特点出发,对建立这些模型的思路和具体方法进行了分析和比较。