辛伐他汀对高脂血症大鼠肾小管间质病变及其ILK表达的影响

目的： 探讨辛伐他汀对高脂诱导的大鼠肾组织整合素连接激酶（ILK）的表达及其对肾小管间质损害的影响。方法：54只Wistar大鼠随机分3组：高脂饮食组给予高脂饲料喂养,辛伐他汀组用高脂饲料喂养同时,给予辛伐他汀10 mg·kg-1·d-1干预,正常对照组给予正常饮食。实验第4周、10周及20周后各组分别随机取6只大鼠处死,取血清及肾组织标本,测定血脂水平、HE染色观察大鼠肾小管-间质损害程度,用Western印迹及免疫组化染色观察大鼠肾间质ILK的表达。结果：与正常对照组比较,从第4周开始,高脂饮食组及辛伐他汀组大鼠血脂水平升高,肾小管上皮细胞逐渐出现融合、浊肿、坏死,肾小管萎缩,管腔结构消失,炎症细胞浸润,间质纤维化,残余的小管上皮出现空泡变性,管壁变薄,代偿性扩张,肾组织ILK的表达明显增加,且随着喂养时间延长,上述指标变化更加明显;而辛伐他汀组与相同时点高脂饮食组比较,上述指标均明显减轻。结论: 高脂饮食大鼠存在有明显的肾小管间质损害,并可能与肾组织ILK表达明显增多密切相关,辛伐他汀可能通过抑制肾小管间质ILK的表达,减轻高脂饮食大鼠肾小管间质病变。     

局部注射辛伐他汀对骨质疏松大鼠股骨髁骨小梁的改建效应

背景：局部注射具有成骨作用的辛伐他汀,可显著增加骨质疏松大鼠股骨颈及股骨髁部的骨密度及力学强度,分析局部注射辛伐他汀对股骨髁骨小梁的影响。 目的：进一步研究骨质疏松大鼠股骨内局部注射辛伐他汀对股骨髁骨小梁的影响。为将辛伐他汀应用于临床骨质疏松局部治疗提供实验基础。 方法：18只雌性SD大鼠双侧卵巢切除后3个月,制备大鼠骨质疏松模型。实验大鼠随机数字表法均分为3组,分别在实验大鼠的右侧股骨髓腔内单次注射辛伐他汀溶液5 mg、10 mg,对照组单纯注射空白载体。分别在注射后1个月处死大鼠并取材。Micro-CT扫描并定量分析骨组织形态变化。 结果与结论：给药后1个月,Micro-CT扫描结果显示,辛伐他汀治疗组的骨微结构参数如骨皮质厚度、骨小梁密度及连接率明显优于对照组。说明疏松骨骼单次注射小剂量辛伐他汀可显著促进股骨髁部骨小梁改建,改善骨骼微结构,可为强化局部、防治骨质疏松骨折的新选择进一步提供实验基础。     

辛伐他汀和吉非罗齐对高脂血症伴骨量减少患者骨代谢和骨密度的影响

目的观察辛伐他汀和吉非罗齐对高胆固醇血症伴骨量减少患者骨代谢指标及骨密度的影响。方法高脂血症合并骨量减少患者128例,分两组后分别予以辛伐他汀和吉非罗齐治疗,并在治疗前及治疗后分别检测血脂、骨吸收标志物血清I型胶原羧基末端肽（sCTX）、骨形成标志物总骨Ⅰ型前胶原N端肽（P1NP）和桡骨远端骨密度（BMD）。结果辛伐他汀组平均治疗周期（10.24±1.89）个月,治疗后总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白（LDL-C）明显降低（P〈0.05）,同时sCTX降低（P〈0.01）,P1NP增高（P〈0.05）,BMD增加（P〈0.01）,而吉非罗齐治疗后虽TC、TG、LDL-C明显降低（P〈0.05）但sCTX、P1NP和BMD无明显变化。结论较大剂量辛伐他汀具有抑制骨吸收、增强骨形成和增加BMD的作用,可能与血脂水平降低无关。     

辛伐他汀对兔动脉粥样硬化血清TNF-α和IFN-γ水平的影响

目的探讨辛伐他汀对兔动脉粥样硬化血清TNF-α和IFN-γ的影响。方法 15只雄性大耳白兔随机分为高脂饮食组,对照组(B组),辛伐他汀组,每组5只。高脂饮食组兔饲喂高脂饲料15周。对照组兔给予普通饲料喂养15周。辛伐他汀组饲喂高脂饮食及辛伐他汀2.5mg/kg/d。于实验前及15周末处死动物前,经耳缘静脉空腹取血,应用全自动生化分析仪检测血清总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)的含量,酶联免疫法测定血清肿瘤坏死因子(TNF-α)及γ-干扰素(IFN-γ)的浓度。分离腹主动脉行HE染色,光学显微镜观察。结果血清TG、TC、LDL-C、TNF-α和IFN-γ的水平高脂饮食组显著增高于对照组(0.05),辛伐他汀组显著低于高脂饮食组,但仍高于对照组,二者呈显著正相关。结论辛伐他汀可显著降低兔动脉粥样硬化血清TG、TC、LDL-C、TNF-α及IFN-γ水平,提示其有治疗前景。     

辛伐他汀对食饵性兔动脉粥样硬化形成中血栓素、前列环素的作用及意义

目的 采用食饵性兔动脉粥样硬化(AS)模型,探讨辛伐他汀对AS形成过程中血管内皮系统及纤溶系统的作用。方法 雄性新西兰兔42只,随机分为正常对照组、AS组(高脂喂饲)和辛伐他汀组(高脂喂饲+辛伐他汀5mg/kg·d)。在实验前、造模第8及12周末分别测定主动脉AS面积、血清胆固醇(TC)、甘油三酯(TG)、血浆6-酮-前列腺素_(1α)(6-keto-PGE(1α))、血栓素B_2(TXB_2)。结果 随实验进程,AS组及辛伐他汀组TC、TG及主动脉AS面积均较正常对照组逐渐升高(P<0.01),辛伐他汀组TC、TG及主动脉AS面积低于同期AS组(P<0.05～0.01);AS组及辛伐他汀组6-keto-PGF_(1α)、TXB_2均显著低于同期正常对照组(P<0.01),但动态观察AS组及辛伐他汀组6-keto-PCF_(1α)与TXB_2无显著差异。结论辛伐他汀对血栓素及前列腺素代谢无直接作用,支持辛伐他汀保护内皮、血小板及对抗炎症作用有限,并不能完全消除AS危险因素。     

Calvarial defect healing by recruitment of autogenous osteogenic stem cells using locally applied simvastatin

Local statins implant has been shown to promote bone healing, the underlying mechanisms are unclear. The purpose of this study was to test the effect of local simvastatin implant on bone defect healing; to evaluate the mobilization, migration, and homing of bone marrow-derived mesenchymal stem cells (BMSCs) and endothelial progenitor cells (EPCs) induced by simvastatin. We found that local simvastatin implant increased bone formation by 51.8% (week 6) and 64.8% (week 12) compared with polyglycolic acid controls (P < 0.01), as verified by X-ray, CT, and histology. Simvastatin increased migration capacity of BMSCs and EPCs in vitro (P < 0.05). Local simvastatin implant increased mobilization of EPCs to the peripheral blood by 127% revealed by FACS analysis (P < 0.01), and increased osteogenic BMSCs to the peripheral blood dramatically revealed by Alizarin Red-S staining for mineralized nodules formation. Pre-transplanted GFP-transfected BMSCs as a tracing cell and bioluminescence imaging revealed that local simvastatin implant recruited GFP-labeled BMSC. Also, local simvastatin implant induced the HIF-1α and BMP-2 expression. In conclusion, local simvastatin implantation promotes bone defect healing, where the underlying mechanism appears to involve the higher expression of HIF-1α and BMP-2, thus recruit autogenous osteogenic and angiogenetic stem cells to the bone defect area implanted with simvastatin.     

骨髓基质干细胞成骨分化过程中Wnt、骨形态发生蛋白2信号通路相关因子与辛伐他汀的作用

背景：辛伐他汀可促进体外培养的人或鼠骨髓基质干细胞向成骨细胞分化,但作用机制尚不清楚。 目的：观察辛伐他汀对大鼠骨髓基质干细胞向成骨细胞分化过程中Wnt与骨形态发生蛋白2信号途径中相关因子表达的影响。 方法：取6周龄雌性SD大鼠双侧股骨、胫骨全骨髓进行体外成骨细胞诱导培养。实验分为对照组及SIM组。SIM组加入浓度为10-7 mol/L辛伐他汀,对照组加入等量无水乙醇和PBS。培养14 d,行碱性磷酸酶染色,28 d时,行von Kossa染色观察细胞外基质矿化情况;培养14,21 d,免疫荧光细胞化学染色观察成骨细胞中β-catenin,Smad1/5,Cbfa1的表达及分布。  结果与结论：大鼠骨髓基质干细胞经体外诱导后可分化为具有碱性磷酸酶活性和矿化细胞外基质能力的成熟成骨细胞。辛伐他汀可显著上调骨髓基质干细胞成骨分化过程中碱性磷酸酶的表达。同时,与对照组比较,SIM组β-catenin,Smad1/5,Cbfa1表达明显增多(P < 0.05),且呈现明显的核内聚集趋势。说明辛伐他汀促进骨髓基质干细胞向成骨细胞分化的作用可能与调控Wnt与骨形态发生蛋白2信号通路中相关因子的表达及细胞内分布有关。     

Preventive effect of simvastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on coronary atherosclerosis in cholesterol-fed rabbits

A study was made on the effect of simvastatin (the generic name of MK-733), a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, on coronary atherosclerosis in cholesterol-fed rabbits with focus on the serum lipids and morphology. Twenty-seven Japanese white rabbits were divided according to dosage of simvastatin into four groups as follows, group P (placebo, 5 rabbits), group MK 1 (simvastatin 1mg/kg, 5 rabbits), group MK 3 (simvastatin 3mg/kg, 6 rabbits) and group MK 5 (simvastatin 5mg/kg, 5 rabbits). They were placed on a 0.5% cholesterol atherogenic diet for 16 weeks and measurements were made of the concentration of serum lipids weekly. After sacrifice, the degree of surface involvement (SI) of aorta stained with Sudan III and the degree of coronary stenosis (CS) of the left circumflex artery were measured using an image-processing system. Serum total cholesterol (TC) level and beta-lipoprotein level decreased dose-dependently in MK groups compared with group P. High density lipoprotein cholesterol level increased in groups MK 3 and MK 5 slightly. Triglyceride level decreased in groups MK 3 and MK 5. The progressions of SI and CS were suppressed in MK groups dose-dependently. Integrated TC, that is, sum of the serum TC values obtained at each week multiplied by 7 corresponded more closely to CS than SI. Intimal thickening constructed from large foam cells originated from macrophages and proliferating smooth muscle cells included lipid droplets in MK groups was almost similar in group P. But it was likely that lipid droplets in each smooth muscle cell in MK groups were less than in group P. In conclusion, the development of coronary atherosclerosis in cholesterol-fed rabbits was suppressed dose-dependently by simvastatin and it was suggested that this preventive effect was due to reducing the integrated TC and local action to vessel walls by simvastatin. (Fukuoka Acta Med.)     

动脉粥样硬化小鼠肝脏脂质代谢相关的PPAR-γ/LXR-α/ABCG1通路及炎症因子的变化和化瘀祛痰方在其中的作用

目的:观察动脉粥样硬化(AS)小鼠肝脏脂质代谢相关的过氧化物酶体增殖物激活受体γ(PPAR-γ)/肝X受体α(LXR-α)/ATP结合盒转运体G1(ABCG1)通路和炎症因子的变化,以及化瘀祛痰方在其中的作用,探讨化瘀祛痰方对肝脏脂质代谢及炎症反应的影响及作用机制。方法:将24只ApoE-/-小鼠随机分为模型组、化瘀祛痰方组和辛伐他汀组,8只C57BL/6J小鼠作为正常对照组。除正常对照组给予基础饲料外,其余各组给予高脂饲料。造模12周后,灌胃给药,化瘀祛痰方组与辛伐他汀组给予相应药物,正常对照组与模型组给予等体积的生理盐水。8周后用全自动生物化学分析仪检测血清甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C)的含量;HE和油红O染色观察肝脏组织病理及脂质的变化情况;ELISA法检测肝脏游离脂肪酸(FFA)、TG、肿瘤坏死因子α(TNF-α)、Toll样受体4(TLR4)和白细胞介素1β(IL-1β)的含量;Western blot法检测PPAR-γ、LXR-α和ABCG1的蛋白表达。结果:与正常对照组比较,模型组小鼠血清TC、TG和...     

组蛋白去乙酰化酶在卵巢切除小鼠骨髓间充质干细胞中的表达

背景：骨髓间充质干细胞的多向分化能力在骨代谢疾病中发挥重要作用,受激素、细胞因子等多种因素调节。目前骨髓间充质干细胞骨向分化的表观遗传学调控机制尚不明确,组蛋白去乙酰化酶与骨质疏松的关系尚需进一步探讨。 目的：建立雌激素缺乏骨质疏松小鼠的实验动物模型,检测骨髓间充质干细胞组蛋白去乙酰化酶1,3,4 mRNA表达水平,探索卵巢切除小鼠骨组织形成障碍的表观遗传学机制。 方法：昆明种小鼠30只随机等分为模型组和假手术组。小鼠适应性喂养7 d后,模型组小鼠切除双侧卵巢,造成雌激素缺乏骨质疏松实验动物模型,假手术组小鼠仅切除等量脂肪组织。 结果与结论：模型组小鼠股骨骨小梁稀疏或断裂,骨小梁宽度变窄,骨小梁间距变宽,骨小梁占视野面积降低。与假手术组相比,模型组小鼠骨髓间充质干细胞中组蛋白去乙酰化酶3 mRNA表达水平显著降低,组蛋白去乙酰化酶1,4表达水平变化差异无显著性意义。提示雌激素缺乏导致骨髓间充质干细胞去乙酰化状态改变可能是骨形成障碍的重要原因之一。中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程全文链接：     

加味二至丸通过抑制铁死亡减轻高脂血症小鼠肝脏脂质沉积

目的:观察加味二至丸对高脂血症模型小鼠肝脏脂质沉积及铁死亡相关蛋白表达的影响.方法:30只ApoE?/?小鼠随机分为模型组、辛伐他汀组和加味二至丸组,每组10只,另取10只相同背景的C57BL/6J小鼠作为正常对照组.模型组及各治疗组均给予高脂饲料喂养,正常对照组给予普通饲料喂养.造模12周后按分组分别给予相应的药物灌...     

Defective Bone Microstructure in Hydronephrotic Mice: A Histomorphometric Study in ICR/Mlac‐hydro Mice

Chronic renal impairment can lead to bone deterioration and abnormal bone morphology, but whether hydronephrosis is associated with bone loss remains unclear. Herein, we aimed to use computer‐assisted bone histomorphometric technique to investigate microstructural bone changes in Imprinting Control Region (ICR) mice with a spontaneous mutation that was associated with bilateral nonobstructive hydronephrosis (ICR/Mlac‐hydro). The results showed that 8‐week‐old ICR/Mlac‐hydro mice manifested decreases in trabecular bone number and thickness, and an increased trabecular separation, thereby leading to a reduction in trabecular bone volume compared with the wild‐type mice. Furthermore, histomorphometric parameters related to both bone resorption and formation, that is, eroded surface, osteoclast surface, and osteoblast surface, were much lower in ICR/Mlac‐hydro mice than in the wild type. A decrease in moment of inertia was found in ICR/Mlac‐hydro mice, indicating a decrease in bone strength. In conclusion, ICR/Mlac‐hydro mice exhibited trabecular bone loss, presumably caused by marked decreases in both osteoblast and osteoclast activities, which together reflected abnormally low bone turnover. Thus, this mouse strain appeared to be a valuable model for studying the hydronephrosis‐associated bone disease. Anat Rec, 297:208–214, 2014. © 2013 Wiley Periodicals, Inc.     

Response of trabecular bone,thyroid C and follicular cells to synthetic salmon calcitonin in middle‐aged orchidectomized male rats

In contrast to studies in women, male osteoporosis is poorly understood and strictly related to advancing age. Among the first antiresorptive substances used in the prevention and treatment of osteoporosis is calcitonin (CT), a hypocalcemic hormone that potently inhibits osteoclastic bone resorption. Natural CT is produced and secreted by thyroid C‐cells. The other endocrine population of thyroid cells produces thyroid hormones (TH), which also affect bone turnover. The aim of this study was to evaluate the influence of salmon CT on trabecular bone microarchitecture with special reference to effects on the structure and function of both CT‐ and TH‐producing thyroid cells in orchidectomized (Orx) middle‐aged rats. Twenty‐four male Wistar rats aged 15 months were randomly divided into Orx and sham‐operated (SO) groups. One group of Orx animals received (s.c.) synthetic salmon CT (Orx + CT; 100 IU kg⁻¹ b.w.) subcutaneously every second day for 6 weeks. The second Orx group and SO rats were given the same volume of vehicle alone by the same schedule. Trabecular bone histomorphometrical parameters were: cancellous bone area (B.Ar), trabecular thickness (Tb.Th), trabecular number (Tb.N) and trabecular separation (Tb.Sp) were obtained with an ImageJ public‐domain image‐processing program. The peroxidase–antiperoxidase method was applied for localization of CT in C‐cells. Anti‐human CT antisera served as the primary antibodies. For immunohistochemical characterization of vascular endothelial growth factor (VEGF) in thyroid tissue, rabbit antisera against human VEGF, served as primary antibodies. CT‐immunopositive thyroid C‐cells, thyroid follicular epithelium, interstitium and colloid were evaluated morphometrically. Blood serum samples were analyzed for CT, osteocalcin (OC), and thyroxine (T₄), and calcium (Ca²⁺) concentration was determined in urine samples. Salmon CT application significantly increased B.Ar, TbTh and TbN, but markedly decreased Tb.Sp. Administration of exogenous CT significantly decreased mean volume (Vc) and relative volume density (Vv) of thyroid C‐cells in relation to both SO and Orx groups. The Vv of the colloid was higher, whereas the V_V of the follicular epithelium was lower after CT treatment compared with Orx alone. CT treatment markedly elevated serum CT, whereas serum OC, T₄ and urinary Ca²⁺ concentrations were lower than in the Orx group. These results indicate that salmon CT stimulates trabecular bone microarchitecture, strongly inhibits thyroid C‐cells and changes the structure of the thyroid gland, indicating hypoactivity.     

Osteosclerotic prostate cancer metastasis to murine bone are enhanced with increased bone formation

Spontaneous development of osteoblastic lesions of prostate cancer (PCa) in mice is modeled by orthotopic (intraprostatic) deposition of neoplastic cells followed by an extremely long latency associated with low incidence of spontaneous bone metastasis. Intracardial injection results in overt bone metastases only with osteoclastic PCa cells (i.e., PC-3). Herein, we report that androgen independent osteoblastic PCa cells readily colonize bone when in a high remodeling state. SCID/Beige mice were subjected to periods of intermittent human parathyroid hormone 1–34 (hPTH) exposure, followed by an intracardiac infusion of osteoblastic C4-2 PCa cells. At the time of PCa infusion, analysis of bone turnover markers from mice treated with hPTH revealed significant increases in osteocalcin (55.06 ± 7.5 vs. 74.01 ± 18.5 ng/ml) and TRAcP-5b (3.3 ± 0.6 vs. 4.81 ± 0.8 U/l), but no change in type I collagen C-terminal teleopeptide levels relative to control mice. Analysis of femoral cancellous bone architecture revealed significant increases in bone mineral density, trabecular thickness (0.056 ± 0.002 vs. 0.062 ± 0.001 mm) and porosity, but significant decreases in connectivity density and trabecular number in hPTH treated mice relative to controls. By 8 weeks post-infusion, 70% of mice pre-treated with hPTH demonstrated detectable serum prostate specific antigen (PSAs) ranging between 2 and 18.8 ng/ml. Immuno-histochemical labeling of femurs for PSA and pan-Cytokeratin revealed the presence of significant tumor cell nests in marrow and trabecular spaces. These results suggest that: (1) local bone physiology is an important factor for developing osteoblastic/sclerotic PCa bone metastases in murine hosts; (2) the establishment of osteosclerotic PCa bone metastases in mice is enhanced by alterations that drive bone formation.     

辛伐他汀涂层内固定对大鼠骨质疏松骨折愈合晚期的影响

背景：降脂类药物辛伐他汀具有一定的促进骨形成作用潜能,局部应用效果更佳。先前研究对骨质疏松大鼠骨折愈合中期的观察证实辛伐他汀涂层内固定可促进骨质疏松大鼠骨折愈合,但其对骨折愈合晚期的影响未见报道。 目的：观察局部应用辛伐他汀涂层内固定对骨质疏松大鼠骨折愈合晚期进程的影响。 方法：将雌性SD大鼠分为单纯骨折组、骨质疏松性骨折组及辛伐他汀干预组。单纯骨折组仅暴露腹腔卵巢不予切除,其余2组采用双侧卵巢切除法建立骨质疏松模型。卵巢切除后6周,所有大鼠建立股骨中段开放性骨折模型,单纯骨折组、骨质疏松性骨折组及辛伐他汀干预组分别采用无涂层、聚乳酸涂层和辛伐他汀复合聚乳酸涂层克氏针内固定。骨折造模后12周分析骨折侧股骨骨密度,X射线摄片和苏木精-伊红染色分析骨折愈合情况,免疫组织化学分析骨形态发生蛋白2在骨折局部的表达。 结果与结论：骨密度检测结果提示股骨全长及中段骨密度骨质疏松性骨折组、辛伐他汀干预组显著低于单纯骨折组,辛伐他汀干预组骨折部位骨密度显著高于骨质疏松性骨折组。X射线摄片结果提示,单纯骨折组骨折两端对位、对线良好,骨痂与骨皮质密度接近相同并相互连接,塑形基本完成;骨质疏松性骨折组愈合质量差,骨痂密度浅淡,部分标本仍见模糊的骨折线;辛伐他汀干预组骨折线消失,骨痂填满骨缺损,骨膜反应深,单纯骨折组、辛伐他汀干预组X射线评分显著高于骨质疏松性骨折组(P < 0.05)。苏木精-伊红染色提示,骨质疏松性骨折组骨折愈合进程较单纯骨折组延迟,辛伐他汀干预组骨小梁较骨质疏松性骨折组更规则有序。免疫组化结果提示各组大鼠骨形态发生蛋白2的表达水平差异无显著性意义。提示辛伐他汀局部应用可有效促进骨质疏松大鼠骨折愈合。中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程全文链接：     

Growth‐dependent phenotype in FasL‐deficient mandibular/alveolar bone

FASL (CD178) is known for its role in triggering apoptosis, mostly in relation with immune cells but additional functions have been reported more recently, including those in bone development. Examination of postnatal FasL‐deficient mice (gld) showed an increased bone deposition in adult mice when compared with wild types. However, a different phenotype was observed prenatally, when the gld bone was underdeveloped. The aim of the following investigation was to evaluate this indication for an growth‐dependent bone phenotype of gld mice and to search for the ‘switch point’. This study focused on the mandibular/alveolar bone as an important structure for tooth anchorage. In vivo micro‐computed tomography (CT) analysis was performed at different stages during the first month (6, 12 and 24 days) of postnatal bone development. In 6‐day‐old gld mice, a decrease in bone volume/tissue volume (BV/TV), trabecular thickness and trabecular number was revealed. In contrast, the 12‐day‐old gld mice showed an increased BV/TV and trabecular thickness in the alveolar bone. The same observation applied for bone status in 24‐day‐old gld mice. Therefore, changes in the bone phenotype occurred between day 6 and 12 of the postnatal development. The switch point is likely related to the changing proportion of bone cells at these stages of development, when the number of osteocytes increases. Indeed, the immunohistochemical analysis of FASL localized this protein in osteoblasts, whereas osteocytes were mostly negative at examined stages. The impact of FASL particularly on osteoblasts would agree with an earlier in vivo observed effect of FASL deficiency on expression of Mmp2, typical for osteoblasts, in the gld mandibular/alveolar bone. Notably, an age‐dependent bone phenotype was reported in Mmp2‐deficient mice.     

中等强度运动对去卵巢大鼠骨质疏松及骨形态发生蛋白2信号通路的影响

目的 探讨中等强度运动对去卵巢大鼠骨密度、骨质代谢、骨生物力学及骨形态发生蛋白2(BMP-2)信号通路的影响。 方法 将24只成年雌性SD大鼠随机分为假手术组、手术组与运动组，每组8只，假手术组仅切除双侧卵巢周围脂肪组织，手术组、运动组摘除双侧卵巢，摘除卵巢1周后运动组进行中等强度运动训练，共训练12周。12周后，进行股骨骨密度、生物力学、骨代谢、组织学检测，Western blotting检测股骨组织BMP-2、Runt相关转录因子2（Runx2）、Osterix及Smad1/5/8蛋白表达。 结果 手术组、运动组血钙、血磷、血抗酒石酸酸性磷酸酶(TRACP)浓度高于假手术组(P<0.05)，而运动组上述指标低于手术组(P<0.05)。手术组和运动组骨密度低于假手术组(P<0.05)，而运动组高于手术组(P<0.05)。手术组和运动组骨组织生物力学性能低于假手术组(P<0.05)，而运动组高于手术组(P<0.05)。组织学显示，运动组骨质疏松程度轻于手术组，骨组织内BMP-2表达量多于手术组。手术组和运动组BMP-2、Runx2、Osterix及Smad1/5/8蛋白表达低于假手术组(P<0.05)，而运动组上述蛋白表达高于手术组(P<0.05)。 结论 中等强度运动可改善去卵巢大鼠股骨的骨密度、生物力学性能与骨代谢，这一作用可能与BMP-2信号通路有关。     

Femoral peak bone mass and osteoclast number in an animal model of age-related spontaneous osteopenia

Background: SAMP6 was developed as a murine model of age-related spontaneous osteopenia characterized by low peak bone mass. A morphometric study of the growing femur in SAMP6 and sex-matched SAMP2 at 10 days to 4 months of age was done to examine the pathogenic process related to osteopenia. Methods: Age-related changes in cortical bone thickness, femur score, trabecular bone volume, thickness of epiphyseal growth plate, number of osteoclasts, and osteoclast surface were measured with a computerized image analyzer. Osteoclasts were examined cytomorphometrically after TRAP (tartrate resistant acid phosphatase) staining of the femoral sections. Results: Cortical bone thickness and femur score increased significantly with age, while trabecular bone volume decreased significantly. Comparing mean values of cortical bone thickness, femur score and trabecular bone volume, we noted significantly lower mean values in SAMP6 than in SAMP2 mice. These significant inter-stain differences first became evident in 20–40-day-old mice, but there was no significant difference in thickness of the epiphyseal growth plate between the two strains. The mean values of the number of osteoclasts per unit none surface length and of the osteoclast surface in SAMP6 were significantly greater than in age- and sex-matched SAMP2. Histograms of distribution of size of osteoclasts of 40-day-old male mice revealed that larger ones were more frequently seen in SAMP6. Furthermore, the ratio of osteoclasts/TRAP positive cells free in the bone marrow cavity was significantly higher in SAMP6 than in SAMP2. Conclusion: Activated bone resorption may play a role in the osteopenia seen in SAMP6. © 1995 Wiley-Liss, Inc.     

葛根素对妊娠期糖尿病大鼠胰腺组织let-7f 及免疫因子IL-17、IL-23 表达的影响

目的:探究葛根素对妊娠期糖尿病大鼠胰腺组织let-7f 及免疫因子IL-17、IL-23 表达的影响。方法:将120 只大鼠分为正常对照组、空白对照组、辛伐他汀组、葛根素低剂量组、葛根素中剂量组、葛根素高剂量组,正常对照组以基础饲料、其他组以高脂饲料饲喂2 周。辛伐他汀组给予2 mg/ kg 的辛伐他汀,葛根素组按低、中、高剂量分别给予70 mg/ kg、120mg/ kg、170 mg/ kg 葛根素,正常对照组和空白对照组给予等量生理盐水,治疗2 周后,测定6 组大鼠血糖和血脂水平、胰腺组织中let-7f 的表达水平以及血清和胰腺组织中IL-17 和IL-23 的表达情况。结果:治疗后,辛伐他汀组和葛根素组大鼠的FBG、TC 、TG 、FFA 显著低于空白对照组,且随着葛根素剂量的增加,FBG、TC 、TG 、FFA 的水平显著降低(P<0.05),呈剂量依赖性;辛伐他汀组和葛根素组胰腺组织中let-7f 的表达显著高于空白对照组(P<0.05),且呈剂量依赖性;辛伐他汀组和葛根素组血清和胰腺组织中IL-17 和IL-23 的表达显著高于空白对照组(P<0.05),且呈剂量依赖性。结论:葛根素能提高妊娠期糖尿病大鼠胰腺组织let-7f 表达,同时降低血清和胰腺组织中IL-17、IL-23 表达,为妊娠期糖尿病临床治疗提供新的思路和理论依据。     

补骨脂提取物干预骨质疏松模型大鼠骨密度及骨生物力学的变化

文题释义： RANKL/OPG通路：核因子κB受体活化因子配体(receptor activator of NF-κB Ligand,RANKL)/骨保护蛋白在维持成骨与破骨的动态平衡,调节骨代谢功能方面发挥着重要作用。RANKL 可与破骨细胞前体细胞膜表面的核因子κB受体活化因子结合,促进破骨细胞分化和激活,抑制其凋亡,最终促进骨吸收;骨保护蛋白作为RANKL的天然抗体,可与RANKL直接结合,竞争性抑制核因子κB受体活化因子与其的结合,进而抑制破骨细胞分化、成熟,最终抑制骨吸收。生理状态下,体内RANKL与骨保护蛋白的表达保持一定的比例,若二者表达比例失衡,则会造成骨代谢紊乱,导致骨相关疾病发生。 骨生物力学：是骨组织在外力作用下的力学生物学效应,对其进行检测可直接评价骨质量,是评价各种治疗骨丢失措施的最佳方案,其检测指标包括弹性模量、最大载荷、屈服载荷等。 背景：地塞米松作为一种糖皮质激素,长期应用会破坏成骨与破骨的动态平衡,降低骨密度,损伤骨生物力学,调控核因子κB受体活化因子配体(receptor activator of NF-κB ligand,RANKL)/骨保护蛋白通路可能影响地塞米松诱导的骨质疏松症大鼠骨密度及骨生物力学。 目的：探讨基于RANKL/骨保护蛋白通路研究补骨脂提取物对地塞米松诱导骨质疏松症大鼠骨密度及骨生物力学的影响。 方法：SPF级Wistar大鼠肌肉注射地塞米松,建立骨质疏松大鼠模型。选择1×10⁷ TU/mL浓度的慢病毒载体进行实验。将模型大鼠随机分为模型组、空载组(空慢病毒载体)、骨保护蛋白沉默组(含骨保护蛋白基因干扰片段的慢病毒载体)、补骨脂提取物组、补骨脂提取物+骨保护蛋白沉默组,每组12只,另取12只正常大鼠设为对照组。药物处理后,采用骨密度仪测定大鼠左侧股骨骨密度,采用力学实验测试机测定大鼠右侧股骨生物力学指标弹性模量、最大载荷、屈服载荷,测定大鼠股骨骨矿物盐含量,酶联免疫吸附法检测血清中RANKL、骨保护蛋白水平,蛋白免疫印迹法检测骨组织中RANKL、骨保护蛋白表达水平。实验方案经青海大学医学院动物实验伦理委员会批准(批准号为2017081501) 结果与结论：①大鼠骨密度、弹性模量、最大载荷、屈服载荷、骨矿物盐含量、血清中骨保护蛋白水平、骨组织中骨保护蛋白表达：模型组较对照组降低,骨保护蛋白沉默组较模型组降低,补骨脂提取物组较模型组升高,补骨脂提取物+骨保护蛋白沉默组较骨保护蛋白沉默组升高,较补骨脂提取物组降低(均P < 0.05);②大鼠血清中RANKL水平、骨组织中RANKL蛋白表达结果显示,模型组较对照组升高;骨保护蛋白沉默组较模型组升高,补骨脂提取物组较模型组降低,补骨脂提取物+骨保护蛋白沉默组较骨保护蛋白沉默组降低,较补骨脂提取物组升高(均P < 0.05);③模型组与空载组两组间各指标比较无明显变化(P > 0.05);④结果说明,补骨脂提取物可提高地塞米松诱导骨质疏松症大鼠的骨密度,改善其骨生物力学,可能是通过上调骨保护蛋白表达,下调RANKL表达实现的。 ORCID: 0000-0001-9896-6214(周倚墨) 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程