Non-traumatic osteonecrosis of the femoral head(NONFH)is one of the most common orthopedic diseases,influenced by multiple signaling pathways and inflammatory factors.The PI3K/AKT signaling pathway is closely related ...Non-traumatic osteonecrosis of the femoral head(NONFH)is one of the most common orthopedic diseases,influenced by multiple signaling pathways and inflammatory factors.The PI3K/AKT signaling pathway is closely related to various biological processes such as apoptosis,autophagy,and metabolism in cells.Increasing evidence suggests that it plays an important role in the development of femoral head necrosis.This paper aims to explore the mechanism of the PI3K/AKT signaling pathway in the pathogenesis of NONFH by analyzing its regulation of lipid metabolism,cell apoptosis and autophagy,and intravascular coagulation.This study provides new insights for the research of NONFH.展开更多
Objective To investigate the histomorphometric features of the necrotic femoral head of rabbits induced by methylprednisolone combined with lipopolysaccharide. Methods Thirty-two mole adult New Zealand white rabbits w...Objective To investigate the histomorphometric features of the necrotic femoral head of rabbits induced by methylprednisolone combined with lipopolysaccharide. Methods Thirty-two mole adult New Zealand white rabbits were used. Among them, 16 were injected with lipopolysaccharide and methylprednisolone （ osteonecrosis group） , and another 16 were sham-injected with saline （ control group）. Magnetic resonance （MR） imaging was taken for femoral heads of the rabbits in both groups at the end of 2, 4 and 6 weeks after the injection. All the rabbits were then killed 6 weeks later. The femoral heads of the rabbits were collected and processed for histological and histomorphometric analysis. Results Femoral head necrosis occurred in 14 rabbits of the osteonecrosis group which were confirmed by histological evaluation and MR imaging. Osteonecrotic femoral heads, compared to controls, were characterized by lower values of bone volume/tissue volume （ P 〈 0. 01 ）, tabecular thichness （ P 〈 0. 01 ） , osteoid surface/bone surface （ P 〈 0. 05 ）, mineralizing apposition rate （ P 〈 0 05 ）, and bone formation rate/bone surface （ P 〈0. 05 ）. However, tabecular separation and eroded surface/bone surface were higher in osteonecrotic femoral heads than in controls （ P 〈 0. 01 ）. Trabecular number and osteoclast surface/ bone surface did not differ significantly. Conclusion The results demonstrated that osteoporosis was apparent in osteonecrotic femoral heads induced by methylprednisolone and lipopolysaccharide, due mainly to trabecular thinning rather than reduction of trabecular number. This might be due to reduced bone formation combined with increased bone resorption.展开更多
Background Gastrodin,as one of the major components extracted from the Chinese herb Gastrodia elata BI.,has many biologic effects,one of which is anti-apoptosis.Apoptosis is considered to be one of the pathogenetic me...Background Gastrodin,as one of the major components extracted from the Chinese herb Gastrodia elata BI.,has many biologic effects,one of which is anti-apoptosis.Apoptosis is considered to be one of the pathogenetic mechanisms in steroid-induced osteonecrosis of the femoral head （ONFH）.Therefore,we performed this study to investigate whether gastrodin has the potential to prevent steroid-induced ONFH.Methods All 18 male adult Wistar rats were divided equally into three groups：the steroid group,the gastrodin＋steroid group,and the control group.Osteonecrosis was induced by low-dose lipopolysaccharide and subsequent high-dose methylprednisolone.Histomorphometric method was used to determine the incidence of osteonecrosis.Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling （TUNEL） assay was performed to detect apoptotic index of osteocytes and osteoblasts.Real-time PCR and Western blotting were performed to detect mRNA and protein expression of Bax,Bcl-2,and Caspase-3.Fisher＇s exact probability test and one-way analysis of variance （ANOVA） with Turkey＇s post hoc test were used to examine significant differences between groups.Results The incidence of osteonecrosis in the gastrodin＋steroid group （16.7％） was significantly lower than that in the steroid group （83.3％）.According to TUNEL assay,the apoptotic indices in the steroid group,the gastrodin＋steroid group,and the control group were 91.1％,27.1％,and 5.4％,respectively,and the differences were significant between groups.Compared with the control group and the gastrodin＋steroid group,the mRNA and protein expression levels of Bax and Caspase-3 were significantly higher in the steroid group,but the Bcl-2 mRNA and protein expression levels were significantly lower.Conclusion Gastrodin could prevent steroid-induced ONFH by anti-apoptosis.展开更多
The aim of this study is to investigate the effects and possible mechanisms of sodium ferulate (SF) on anti-apoptosis in steroid-induced femoral head osteonecrosis in rabbits. Japanese white rabbits were randomly divi...The aim of this study is to investigate the effects and possible mechanisms of sodium ferulate (SF) on anti-apoptosis in steroid-induced femoral head osteonecrosis in rabbits. Japanese white rabbits were randomly divided into three groups (control group, treatment group, and model group), each with 24 rabbits. The model and treatment groups were first injected with an intravenous dose of horse serum, 10 ml/kg, three weeks later with an intravenous dose of 7.5 ml/kg, and two weeks later with an intramuscular dose of methylprednisolone, 45 mg/kg, three times in order to establish rabbit models of osteonecrosis. Concurrently, the treatment group was injected with intravenous doses of SF 20 mg/kg for two weeks, once per day. Three time points, Weeks 2, 4, and 8, were selected after modeling was completed. Osteonecrosis was verified by histopathology with haematoxylin-eosin (HE) staining. The apoptosis rate of osteonecrosis was observed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The apoptosis expressions of caspase-3 and Bcl-2 were analyzed by immunohistochemistry and Western blot. The rabbit models of osteonecrosis were successfully established and observed by HE staining. SF was effective in intervening in apoptosis and decreasing the apoptosis rate in femoral head necrosis by the immunohistochemistry and TUNEL assay (P<0.01). Western blot analysis indicated that there were statistical significances in the protein levels of caspase-3 and Bcl-2 (P<0.01). SF has a protective effect by reducing the incidence of early steroid-induced femoral head necrosis in rabbits, effectively intervening in apoptosis through decreasing caspase-3 expression and up-regulating Bcl-2 expression.展开更多
目的:激素性股骨头坏死家兔模型是最常用的股骨头坏死动物模型,其股骨头病理学改变与临床较为接近,但目前国内外报道的造模条件、方法和评价标准等均不统一,导致所建立动物模型的科学价值低、难于推广应用。此次研究旨在明确不同造模条...目的:激素性股骨头坏死家兔模型是最常用的股骨头坏死动物模型,其股骨头病理学改变与临床较为接近,但目前国内外报道的造模条件、方法和评价标准等均不统一,导致所建立动物模型的科学价值低、难于推广应用。此次研究旨在明确不同造模条件对激素性股骨头坏死家兔模型建立的影响,分析模型成功建立的适宜条件。方法:检索中国知网、万方、维普、中国生物医学文献服务系统、Web of Science、PubMed和EMbase数据库中截至2022-04-01前有关激素性股骨头坏死家兔造模的文献,依据纳排标准以及文献质量评价等完成对文献的筛选并提取文献中结局指标数据,运用RevMan、Stata和ADDIS统计软件对纳入数据进行Meta分析。结果:(1)最终纳入82篇文献,共1366只家兔纳入研究,激素性股骨头坏死造模方法分为单纯激素法、激素联合脂多糖法和激素联合血清法3种,其中单纯激素法33篇文献,激素联合脂多糖法20篇文献,激素联合血清法29篇文献;(2)Meta分析结果显示,3种造模方法均能显著增加激素性股骨头坏死家兔股骨头空骨陷窝率(P<0.001),显著降低激素性股骨头坏死家兔股骨头骨小梁面积比(P<0.001);各造模方法的空骨陷窝率排序结果为:激素联合脂多糖法>单纯激素法>激素联合血清法>正常组;骨小梁面积比排序结果:正常组>激素联合血清法>单纯激素法>激素联合脂多糖法;(3)亚组分析结果提示:单纯激素诱导的家兔模型空骨陷窝率可能与家兔品种和造模用激素种类有关(组间差异P<0.05),其中新西兰白兔合并效应量高于中国白兔(P<0.05)和日本白兔,地塞米松合并效应量高于其他激素种类;激素联合脂多糖诱导的模型空骨陷窝率与激素种类和脂多糖给药模式有关(组间差异P<0.05),其中甲泼尼龙琥珀酸钠合并效应量显著高于其他激素种类(P<0.05),泼尼松龙合并效应量显著低于其他激素种类(P<0.05),脂多糖100μg/kg×2次的合并效应量显著低于10μg/kg×2次和50μg/kg×2次(P<0.05);激素联合血清诱导的模型空骨陷窝率与激素种类和血清剂量有关(组间差异P<0.05),其中地塞米松磷酸钠合并效应量显著高于其他激素种类(P<0.05),地塞米松合并效应量显著低于其他激素种类(P<0.05),血清“10 mL/kg+6 mL/kg”组合剂量的合并效应量低于其他血清剂量(P<0.05)。结论:(1)以空骨陷窝率和骨小梁面积比作为模型成功建立的判断标准,3种造模方法都可成功构建家兔激素性股骨头坏死模型,其中激素联合脂多糖法最优;(2)选择单纯激素法时建议使用新西兰白兔和地塞米松,选择激素联合脂多糖法时建议使用甲泼尼龙琥珀酸钠和低剂量脂多糖,选择激素联合血清造模法时建议使用地塞米松磷酸钠。展开更多
目的探讨烙灸治疗早期激素性股骨头坏死(steroid-induced osteonecrosis of the femoral head,SONFH)的作用机制。方法将新西兰兔按随机数表法分为空白组、模型组、烙灸组、抑制剂组,每组6只,采用内毒素联合激素的方法制备SONFH模型。...目的探讨烙灸治疗早期激素性股骨头坏死(steroid-induced osteonecrosis of the femoral head,SONFH)的作用机制。方法将新西兰兔按随机数表法分为空白组、模型组、烙灸组、抑制剂组,每组6只,采用内毒素联合激素的方法制备SONFH模型。烙灸组进行4周的烙灸治疗,抑制剂组给予IκBα磷酸化抑制剂Bay11-7082(1 mg·kg-1)腹腔注射3周。干预前后分别观察实验兔一般状况变化;HE染色观察各组实验兔股骨头组织病理学变化;Western blot和RT-qPCR分别检测股骨头组织中IKKβ、磷酸化IκBα(p-IκBα)蛋白及mRNA的表达变化;ELISA检测血清中核因子κB(nuclear factor kappa-B,NF-κB)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-6(interleukin-6,IL-6)水平。结果与空白组比较,模型组实验兔逐渐出现精神萎靡、毛发暗淡等情况,股骨头组织骨小梁出现断裂、稀疏等改变,IKKβ、p-IκBα蛋白水平,IKKβmRNA水平及血清中NF-κB、TNF-α、IL-6水平均升高(P均<0.05);与模型组比较,烙灸组股骨头组织病理学改善,IKKβ、p-IκBα蛋白水平,IKKβmRNA水平及血清中NF-κB、TNF-α、IL-6水平均降低(P均<0.05),而IκBα蛋白及mRNA表达均升高(P均<0.05)。结论烙灸可改善早期SONFH骨代谢,缓解骨坏死,其机制与抑制TLR4/NF-κB通路有关。展开更多
探讨整体观念指导下激素性股骨头坏死(steroid-induced osteonecrosis of the femoralhead,SONFH)的分子生物学机理,为SONFH的中医药防治提供理论依据,指出长期大剂量使用激素是导致股骨头坏死的主要病因,发病机制主要与脂质代谢紊乱学...探讨整体观念指导下激素性股骨头坏死(steroid-induced osteonecrosis of the femoralhead,SONFH)的分子生物学机理,为SONFH的中医药防治提供理论依据,指出长期大剂量使用激素是导致股骨头坏死的主要病因,发病机制主要与脂质代谢紊乱学说、静脉淤滞骨内高压学说、血管内凝血与血管损伤学说、骨髓间充质干细胞成脂分化学说、骨质疏松学说、骨细胞凋亡学说和基因控制学说等有关。展开更多
背景:激素性股骨头坏死是非创伤性股骨头坏死的关键危险因素,近年来发病率逐渐上升,但其具体发病机制尚不清楚,寻找一个合理的动物模型对于疾病研究及治疗至关重要。目的:综述近年来常用的激素性股骨头坏死动物模型,分析不同造模方式和...背景:激素性股骨头坏死是非创伤性股骨头坏死的关键危险因素,近年来发病率逐渐上升,但其具体发病机制尚不清楚,寻找一个合理的动物模型对于疾病研究及治疗至关重要。目的:综述近年来常用的激素性股骨头坏死动物模型,分析不同造模方式和评价标准的优缺点,为后续研究提供参考。方法:以“股骨头坏死,激素性股骨头坏死,动物模型,femoral head necrosis,osteonecrosis of the femoral head,steroid-induced osteonecrosis of the femoral head,animal model”为关键词,在中国知网、万方及Pub Med等数据库中检索2013-2023年发表的文献,根据纳入标准,纳入61篇文献进行综合分析,其中英文文献38篇,中文文献23篇。结果与结论:(1)兔子、大鼠和鸡是目前在激素性股骨头坏死模型研究中应用较多的动物;(2)激素联合脂多糖或马血清建模死亡率低,模型成功率高,稳定性强;(3)组织病理学是评价模型金标准,但需要终止实验,不利于后续实验研究,所以寻找一种无创替代方法仍是未来的努力方向;(4)目前尚未探索出一种理想激素性股骨头坏死动物模型,未来研究者需继续努力早日在该领域实现突破。展开更多
文摘Non-traumatic osteonecrosis of the femoral head(NONFH)is one of the most common orthopedic diseases,influenced by multiple signaling pathways and inflammatory factors.The PI3K/AKT signaling pathway is closely related to various biological processes such as apoptosis,autophagy,and metabolism in cells.Increasing evidence suggests that it plays an important role in the development of femoral head necrosis.This paper aims to explore the mechanism of the PI3K/AKT signaling pathway in the pathogenesis of NONFH by analyzing its regulation of lipid metabolism,cell apoptosis and autophagy,and intravascular coagulation.This study provides new insights for the research of NONFH.
基金Supported by National Nature Science Foundation of China (30571898)
文摘Objective To investigate the histomorphometric features of the necrotic femoral head of rabbits induced by methylprednisolone combined with lipopolysaccharide. Methods Thirty-two mole adult New Zealand white rabbits were used. Among them, 16 were injected with lipopolysaccharide and methylprednisolone （ osteonecrosis group） , and another 16 were sham-injected with saline （ control group）. Magnetic resonance （MR） imaging was taken for femoral heads of the rabbits in both groups at the end of 2, 4 and 6 weeks after the injection. All the rabbits were then killed 6 weeks later. The femoral heads of the rabbits were collected and processed for histological and histomorphometric analysis. Results Femoral head necrosis occurred in 14 rabbits of the osteonecrosis group which were confirmed by histological evaluation and MR imaging. Osteonecrotic femoral heads, compared to controls, were characterized by lower values of bone volume/tissue volume （ P 〈 0. 01 ）, tabecular thichness （ P 〈 0. 01 ） , osteoid surface/bone surface （ P 〈 0. 05 ）, mineralizing apposition rate （ P 〈 0 05 ）, and bone formation rate/bone surface （ P 〈0. 05 ）. However, tabecular separation and eroded surface/bone surface were higher in osteonecrotic femoral heads than in controls （ P 〈 0. 01 ）. Trabecular number and osteoclast surface/ bone surface did not differ significantly. Conclusion The results demonstrated that osteoporosis was apparent in osteonecrotic femoral heads induced by methylprednisolone and lipopolysaccharide, due mainly to trabecular thinning rather than reduction of trabecular number. This might be due to reduced bone formation combined with increased bone resorption.
基金This work was supported by a grant from the National Natural Science Foundation of China （No. 81301592）.
文摘Background Gastrodin,as one of the major components extracted from the Chinese herb Gastrodia elata BI.,has many biologic effects,one of which is anti-apoptosis.Apoptosis is considered to be one of the pathogenetic mechanisms in steroid-induced osteonecrosis of the femoral head （ONFH）.Therefore,we performed this study to investigate whether gastrodin has the potential to prevent steroid-induced ONFH.Methods All 18 male adult Wistar rats were divided equally into three groups：the steroid group,the gastrodin＋steroid group,and the control group.Osteonecrosis was induced by low-dose lipopolysaccharide and subsequent high-dose methylprednisolone.Histomorphometric method was used to determine the incidence of osteonecrosis.Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling （TUNEL） assay was performed to detect apoptotic index of osteocytes and osteoblasts.Real-time PCR and Western blotting were performed to detect mRNA and protein expression of Bax,Bcl-2,and Caspase-3.Fisher＇s exact probability test and one-way analysis of variance （ANOVA） with Turkey＇s post hoc test were used to examine significant differences between groups.Results The incidence of osteonecrosis in the gastrodin＋steroid group （16.7％） was significantly lower than that in the steroid group （83.3％）.According to TUNEL assay,the apoptotic indices in the steroid group,the gastrodin＋steroid group,and the control group were 91.1％,27.1％,and 5.4％,respectively,and the differences were significant between groups.Compared with the control group and the gastrodin＋steroid group,the mRNA and protein expression levels of Bax and Caspase-3 were significantly higher in the steroid group,but the Bcl-2 mRNA and protein expression levels were significantly lower.Conclusion Gastrodin could prevent steroid-induced ONFH by anti-apoptosis.
基金supported by the Department of Orthopedics, the Second Affiliated Hospital of Xi’an Jiaotong University,China
文摘The aim of this study is to investigate the effects and possible mechanisms of sodium ferulate (SF) on anti-apoptosis in steroid-induced femoral head osteonecrosis in rabbits. Japanese white rabbits were randomly divided into three groups (control group, treatment group, and model group), each with 24 rabbits. The model and treatment groups were first injected with an intravenous dose of horse serum, 10 ml/kg, three weeks later with an intravenous dose of 7.5 ml/kg, and two weeks later with an intramuscular dose of methylprednisolone, 45 mg/kg, three times in order to establish rabbit models of osteonecrosis. Concurrently, the treatment group was injected with intravenous doses of SF 20 mg/kg for two weeks, once per day. Three time points, Weeks 2, 4, and 8, were selected after modeling was completed. Osteonecrosis was verified by histopathology with haematoxylin-eosin (HE) staining. The apoptosis rate of osteonecrosis was observed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The apoptosis expressions of caspase-3 and Bcl-2 were analyzed by immunohistochemistry and Western blot. The rabbit models of osteonecrosis were successfully established and observed by HE staining. SF was effective in intervening in apoptosis and decreasing the apoptosis rate in femoral head necrosis by the immunohistochemistry and TUNEL assay (P<0.01). Western blot analysis indicated that there were statistical significances in the protein levels of caspase-3 and Bcl-2 (P<0.01). SF has a protective effect by reducing the incidence of early steroid-induced femoral head necrosis in rabbits, effectively intervening in apoptosis through decreasing caspase-3 expression and up-regulating Bcl-2 expression.
文摘目的:激素性股骨头坏死家兔模型是最常用的股骨头坏死动物模型,其股骨头病理学改变与临床较为接近,但目前国内外报道的造模条件、方法和评价标准等均不统一,导致所建立动物模型的科学价值低、难于推广应用。此次研究旨在明确不同造模条件对激素性股骨头坏死家兔模型建立的影响,分析模型成功建立的适宜条件。方法:检索中国知网、万方、维普、中国生物医学文献服务系统、Web of Science、PubMed和EMbase数据库中截至2022-04-01前有关激素性股骨头坏死家兔造模的文献,依据纳排标准以及文献质量评价等完成对文献的筛选并提取文献中结局指标数据,运用RevMan、Stata和ADDIS统计软件对纳入数据进行Meta分析。结果:(1)最终纳入82篇文献,共1366只家兔纳入研究,激素性股骨头坏死造模方法分为单纯激素法、激素联合脂多糖法和激素联合血清法3种,其中单纯激素法33篇文献,激素联合脂多糖法20篇文献,激素联合血清法29篇文献;(2)Meta分析结果显示,3种造模方法均能显著增加激素性股骨头坏死家兔股骨头空骨陷窝率(P<0.001),显著降低激素性股骨头坏死家兔股骨头骨小梁面积比(P<0.001);各造模方法的空骨陷窝率排序结果为:激素联合脂多糖法>单纯激素法>激素联合血清法>正常组;骨小梁面积比排序结果:正常组>激素联合血清法>单纯激素法>激素联合脂多糖法;(3)亚组分析结果提示:单纯激素诱导的家兔模型空骨陷窝率可能与家兔品种和造模用激素种类有关(组间差异P<0.05),其中新西兰白兔合并效应量高于中国白兔(P<0.05)和日本白兔,地塞米松合并效应量高于其他激素种类;激素联合脂多糖诱导的模型空骨陷窝率与激素种类和脂多糖给药模式有关(组间差异P<0.05),其中甲泼尼龙琥珀酸钠合并效应量显著高于其他激素种类(P<0.05),泼尼松龙合并效应量显著低于其他激素种类(P<0.05),脂多糖100μg/kg×2次的合并效应量显著低于10μg/kg×2次和50μg/kg×2次(P<0.05);激素联合血清诱导的模型空骨陷窝率与激素种类和血清剂量有关(组间差异P<0.05),其中地塞米松磷酸钠合并效应量显著高于其他激素种类(P<0.05),地塞米松合并效应量显著低于其他激素种类(P<0.05),血清“10 mL/kg+6 mL/kg”组合剂量的合并效应量低于其他血清剂量(P<0.05)。结论:(1)以空骨陷窝率和骨小梁面积比作为模型成功建立的判断标准,3种造模方法都可成功构建家兔激素性股骨头坏死模型,其中激素联合脂多糖法最优;(2)选择单纯激素法时建议使用新西兰白兔和地塞米松,选择激素联合脂多糖法时建议使用甲泼尼龙琥珀酸钠和低剂量脂多糖,选择激素联合血清造模法时建议使用地塞米松磷酸钠。
文摘探讨整体观念指导下激素性股骨头坏死(steroid-induced osteonecrosis of the femoralhead,SONFH)的分子生物学机理,为SONFH的中医药防治提供理论依据,指出长期大剂量使用激素是导致股骨头坏死的主要病因,发病机制主要与脂质代谢紊乱学说、静脉淤滞骨内高压学说、血管内凝血与血管损伤学说、骨髓间充质干细胞成脂分化学说、骨质疏松学说、骨细胞凋亡学说和基因控制学说等有关。
文摘背景:激素性股骨头坏死是非创伤性股骨头坏死的关键危险因素,近年来发病率逐渐上升,但其具体发病机制尚不清楚,寻找一个合理的动物模型对于疾病研究及治疗至关重要。目的:综述近年来常用的激素性股骨头坏死动物模型,分析不同造模方式和评价标准的优缺点,为后续研究提供参考。方法:以“股骨头坏死,激素性股骨头坏死,动物模型,femoral head necrosis,osteonecrosis of the femoral head,steroid-induced osteonecrosis of the femoral head,animal model”为关键词,在中国知网、万方及Pub Med等数据库中检索2013-2023年发表的文献,根据纳入标准,纳入61篇文献进行综合分析,其中英文文献38篇,中文文献23篇。结果与结论:(1)兔子、大鼠和鸡是目前在激素性股骨头坏死模型研究中应用较多的动物;(2)激素联合脂多糖或马血清建模死亡率低,模型成功率高,稳定性强;(3)组织病理学是评价模型金标准,但需要终止实验,不利于后续实验研究,所以寻找一种无创替代方法仍是未来的努力方向;(4)目前尚未探索出一种理想激素性股骨头坏死动物模型,未来研究者需继续努力早日在该领域实现突破。
