FGFR3在骨骼发育和疾病中作用的研究进展

FGFR3是成纤维细胞生长因子受体（Fibroblast growth factor receptors ,FGFRs）家族成员之一,在骨骼发育中起重要作用。FGFR3的激活突变引起一系列骨骼发育缺陷性疾病,如软骨发育不全（achondroplasia,ACH）、季肋发育不全（hypochondroplasia,HCH）和致死性骨发育不全（thanatophoric dysplasia,TD）。目前研究认为,FGFR3在骨骼发育中抑制软骨形成的作用是明确的,但其对骨形成的作用尚不明确,需要进一步研究。     

运动对骨骼—肌腱界面愈合组织的影响

利用纽西兰兔作体内实验，来分析手术后石膏固定，笼内活动，连续被动性活动三种不同的复健方法对肌腱-骨骼间界面愈合组织的影响。结果显示在术后第15天愈合组织所能承受的最大张力，笼内活动组为0.875kg，石膏固定组为2.014kg，是笼内活动组的231.52%，而连续被动性活动组为2.638kg，是笼内活动组的261.35%。石膏固定组虽有很高的张力，但关节内粘连也较多。     

多代连续饮用四种饮水的雌性大鼠骨生物力学性能和骨代谢水平的比较

目的观察雌性SD大鼠多代连续单纯饮用自来水、纯净水、矿物质水和天然水,对其骨质密度、骨生物力学性能及骨代谢的影响。方法取前期实验暴露于四种饮水条件下的F2代断乳健康雌性SD大鼠,各组30只,饮用与F1代相同饮水,除饮水外其他条件完全相同。饲养10个月后处死,腹主动脉取血并分离血清检测大鼠骨碱性磷酸酶（BALP）、骨钙素（BGP）、血清I型前胶原羧基端前肽（PICP）、I型胶原交联羧基末端肽（ICTP）,同时取右侧股骨,进行骨密度和骨生物力学检测。结果血清中BGP含量天然水组高于自来水组（P〈0.05）;PICP含量纯净水组和天然水组低于自来水组（P〈0.01）;ICTP含量天然水组低于自来水组（P〈0.01）。拉伸试验显示：自来水组大鼠股骨最大桡度高于天然水组、矿物质水组和纯净水组（P〈0.01）;自来水组弹性桡度高于天然水组（P〈0.01）和矿物质水组（P〈0.05）。自来水组大鼠股骨最大应变高于天然水组、矿物质水组和纯净水组（P〈0.01）;断裂应变自来水组高于矿物质水组和天然水组（P〈0.01）。杨氏模量自来水组低于天然水组（P〈0.05）。结论长期饮用不同水质的水,可能对大鼠骨骼的生长发育会造成一定的影响。     

酒精摄入对小鼠不同骨骼形态学参数的影响

目的：通过骨组织形态计量学方法探讨和比较酒精摄人对小鼠松质骨和皮质骨形态学参数的影响。方法：清洁级昆明种小鼠30只随机分成3组，基础对照组，正常对照组（蒸馏水灌胃），酒精组给予50％（体积分数）乙醇，按4g·kg^-1·d^-1剂量灌胃，共60d，实验结束后取小鼠胫骨上段、中段经不脱钙骨切片进行骨组织形态计量学参数测量。结果：与正常组比较，酒精组松质骨的形态学参数骨小梁面积百分数（％Tb．Ar）明显降低（-66％，P〈0．05），骨形成率（BFR／TV）降低（-35％，P〈0．05）；皮质骨面积百分率（％Ct．Ar）降低（-7％，P〈0．05）及髓腔面积百分率增加（％Ma．Ar＋32％，P〈0．05），骨内膜骨形成率E—BFR／BS降低（-41％，P〈0．05）。结论：长期摄入酒精使小鼠皮质骨和松质骨骨量均下降，微观结构改变，骨质量下降。     

体脂对DXA骨密度测量结果及骨质疏松诊断的影响

随着社会老龄化和生活水平提高,制约老年人健康长寿的骨质疏松症受到越来越多的重视。双能Ｘ线吸收测量法(dual energy X-ray absorptiometer,DXA)测量骨密度是诊断骨质疏松的金标准,但它的精确性受身体脂肪含量的影响。体脂可以干扰DXA测量骨密度的结果,这可能会导致体脂分布改变显著者（如绝经后体脂分布变化较大的女性）骨质疏松诊断的偏倚,造成此类人群骨质疏松时误诊或漏诊的发生。本文就脂肪对骨密度测量结果及骨质疏松诊断的影响作一综述。     

GnRHa主动免疫对幼鼠子宫发育的作用

目的探讨促性腺激素释放激素激动剂(GnRHa)主动免疫对幼鼠子宫发育的作用。方法 60只昆明雌鼠随机均分为四组,分别颈部皮下注射不同剂量阿拉瑞林抗原,各组均连续注射7 d。在0 d、7 d、14 d和21 d测定体重,于21 d处理小鼠,显微镜观察子宫的组织结构变化,并用Motic imagles软件测定分析图像数据。结果阿拉瑞林能明显抑制子宫的发育,且剂量越大作用越明显。EG-Ⅲ的UWT明显缩小(P<0.05);实验组EET均小于对照组(P<0.05)。EG-Ⅰ子宫腔轻度缩小;EG-Ⅱ子宫腔和腺体管腔缩小,子宫管壁明显变薄;内膜皱襞减少,上皮变薄;EG-Ⅲ子宫壁变薄,子宫腺减少,内膜细胞胞核变小,上皮变薄,胞质明显减少。结论阿拉瑞林主动免疫能显著抑制幼鼠的子宫发育,且连续重复免疫对小鼠具有毒性作用,剂量越大,作用越明显。     

睾酮对小鼠卵泡体外发育的影响

目的探讨高浓度睾酮对体外培养的小鼠卵泡生长发育的影响。方法以出生后12日龄的ICR雌鼠体外培养卵泡为研究模型,将卵泡随机分为以下4个组,每组30个:正常对照组(control组)、10-4mol/L睾酮处理组、10-5mol/L睾酮处理组和10-6mol/L睾酮处理组。将卵泡随机分为以下3个组,每组30个:正常对照组(control组)、睾酮处理组(T组,T=10-5mol/L)和雄激素受体拮抗剂氟他胺预处理后再加睾酮处理组(F+T组,F=10-5mol/L,T=10-5mol/L)。在60mm无菌细胞培养皿上进行微滴培养,每天在倒置显微镜下观察卵泡轮廓,颗粒细胞增生情况,卵母细胞形态以及有无卵母细胞逸出等,并记录卵泡存活和退化的情况。结果 10-4mol/L睾酮能抑制卵泡的生长,而10-5mol/L睾酮能够促进颗粒细胞的增殖和卵泡的生长;同时,在卵泡生长前期,睾酮能刺激卵泡的发育,在后期则呈抑制作用,即卵泡发育停滞、退化或死亡。结论在初级和次级卵泡阶段,10-5mol/L睾酮能促进卵泡的发育,而在窦状卵泡阶段则抑制卵泡的发育。     

补骨脂素对骨质疏松小鼠骨代谢指标和生物力学的影响

目的利用卵巢切除小鼠模型,研究补骨脂素对骨质疏松小鼠骨代谢指标和股骨生物力学的影响。方法 40只雌性C57BL/6小鼠随机分为4组:假手术组(不切除卵巢+生理盐水),模型组(切除卵巢+生理盐水),雌二醇组(切除卵巢+雌二醇),补骨脂素组(切除卵巢+补骨脂素)。给药6周后测定血清碱性磷酸酶、Ⅰ型胶原羧基末端肽和雌激素含量。利用3点弯曲实验对股骨生物力学进行检测。结果与模型组比较,补骨脂素组血清碱性磷酸酶水平升高,但无统计学差异,补骨脂素组和雌二醇组血清I型胶原羧基末端肽水平明显降低。雌二醇组血清雌激素水平较模型组明显升高,补骨脂素组血清雌激素水平仍保持较低水平,与模型组比较无统计学差异。与模型组比较,补骨脂素治疗组小鼠股骨的最大载荷,最大应力和弯曲弹性模量系数指标显著升高。结论补骨脂素作为一种天然植物雌激素可改善骨质疏松小鼠骨代谢指标和股骨生物力学性能。     

Nbn基因对小鼠小脑神经元发育的影响

目的:通过观察神经特异性Nbn基因敲除(Nbn-CNS-del)和对照(Nbn-CNS-Ctr)小鼠小脑神经元发育的形态学变化,探讨DNA损伤修复基因Nbn在小鼠小脑发育过程中的作用.方法:应用免疫组织化学技术和体视学方法对生后(P) 7、 14、 21d的Nbn-CNS-del和Nbn-CNS-Ctr小鼠小脑进行系统观察和定量分析.结果:与Nbn-CNS-ctr小鼠相比,Nbn-CNS-del小鼠生后各时间相点小脑发育迟缓,皮质各层界限不清,细胞排列紊乱,至21d未形成正常小脑皮质的3层结构;NeuN阳性表达的颗粒细胞面数密度和体密度值明显减小;D-28K阳性表达的浦肯野细胞面数密度和体密度值增加.结论:DNA损伤修复基因Nbn可能是小脑发育过程中的重要基因,影响小鼠小脑神经元的发育和成熟.     

Anti-oxidative effect of apocynin on insulin resistance in high-fat diet mice

The present study examines the effects of apocynin on oxidative stress and antioxidant enzymes in high-fat diet (HFD) induced obese mice. After 12 weeks on HFD, the C57BL/6J mice that clearly exhibited insulin resistance received apocynin (2.4g/L) in their drinking water for five weeks. The results show that apocynin treatment significantly ameliorated hyperglycemia, hyperinsulinemia and dyslipidemia in HFD mice. Furthermore, the intraperitoneal glucose tolerance test (IPGTT) and homeostasis model assessment of insulin resistance (HOMA-IR) indicate significant improvement of insulin sensitivity in HFD mice after apocynin treatment. Compared to the HFD control mice, serum malondialdehyde (MDA) was significantly lower and serum superoxide dismutase (SOD) was significantly higher in apocynin treated HFD mice, indicating that apocynin suppressed systemic oxidative stress in the treated group. In the liver, apocynin significantly reduced the level of MDA. Accordingly, apocynin treatment strengthened the antioxidative defense system with an increased activity of SOD, glutathione-peroxidase (GSHpx) and content of reduced glutathione (GSH). We also found that hepatic catalase (CAT) activity significantly decreased after apocynin treatment which may indicate that apocynin reduces hydrogen peroxide and oxidative stress in the liver. These results suggest that apocynin may ameliorate insulin resistance by reducing systemic and hepatic oxidative stress in HFD fed mice.     

Reduction of atherosclerosis despite hypercholesterolemia in lyn-deficient mice fed a high-fat diet

Oxidation and other modifications of serum low-density lipoprotein (LDL) are associated with the development of atherosclerosis, and a scavenger receptor and CD40 signalling are also known to play important roles in the process. We previously showed that the Src family protein-tyrosine kinase Lyn is physically and/or functionally associated with macrophage type-I and type-II class-A scavenger receptors (MSR-A) and CD40. In this study, we addressed whether Lyn is involved in the build-up of serum lipid levels and in atherosclerotic changes. When fed a normal diet, lyn-deficient mice had serum lipid levels that were no different from those of wild-type mice. By contrast, lyn-deficient mice fed a high-fat diet showed serum lipid levels that were much higher than those seen in wild-type mice. Curiously, however, the lyn-deficient mice fed either diet showed no increase in incidence of atherosclerotic lesions compared with wild-type mice. This may be partly explained by our data showing suppression of proliferation of peritoneal macrophages in response to oxidized LDL in the absence of Lyn, and failure of stimulation of the CD40 pathway in lyn-deficient macrophages to induce expression of monocytic chemoattractant protein-1 (MCP-1), which is related to atherosclerosis. These results suggest that Lyn plays an important role in the metabolism of serum lipids and in the development of atherosclerotic lesions on high-fat diets.     

Effects of adrenalectomy and hormone replacement on B6C3F1 mice fed a high-fat diet

Bilateral adrenalectomy (ADX) causes decreased circulating leptin in both obese and lean mice. It remains unclear whether the decreased plasma leptin after ADX is due to decreased adipose tissue or is due to decreased circulating glucocorticoids. The present experiment was performed to test the hypothesis that the absence of glucocorticoids from circulation is sufficient to decrease circulating leptin. Sixty-four adult male B6C3F1 mice were individually housed and fed either Purina rat chow or an experimental diet. After 6 weeks, mice fed the experimental diet gained more weight than mice fed the control diet. Each dietary group was then subdivided into four groups: ADX with cholesterol replacement (ADX-CHOL), ADX with corticosterone (CORT) replacement (ADX+CORT), ADX with aldosterone (ALDO) replacement (ADX+ALDO), and sham operation (SHAM). Two days after surgery, mice were killed and exsanguinated and the carcasses were prepared for gravimetric analyses. Blood was collected and centrifuged and the plasma was assayed for leptin, CORT, and ALDO. Blood glucose was determined using whole blood taken before centrifugation. There was no difference in body weight due to ADX after 2 days. Mice fed the experimental diet had higher circulating leptin than those fed the control diet. The ADX+CORT groups (both experimental and control diets) had higher plasma leptin concentrations than the other groups. No differences were observed between ADX-CHOL and SHAM groups. These results suggest that circulating leptin is not directly controlled by glucocorticoids. The effect of ADX on circulating leptin reported by others may be the consequence of decreased adiposity.     

Abdominal adiposity, insulin and bone quality in young male rats fed a high-fat diet containing soybean or canola oil

OBJECTIVES:

A low ratio of omega-6/omega-3 polyunsaturated fatty acids is associated with healthy bone properties. However, fatty diets can induce obesity. Our objective was to evaluate intra-abdominal adiposity, insulin, and bone growth in rats fed a high-fat diet containing low ratios of omega-6/omega-3 provided in canola oil.

METHODS:

After weaning, rats were grouped and fed either a control diet (7S), a high-fat diet containing soybean oil (19S) or a high-fat diet of canola oil (19C) until they were 60 days old. Differences were considered to be significant if p<0.05.

RESULTS:

After 60 days, the 19S and 19C groups showed more energy intake, body density growth and intra-abdominal fat mass. However, the 19S group had a higher area (200%) and a lower number (44%) of adipocytes, while the 7S and 19C groups did not differ. The serum concentrations of glucose and insulin and the insulin resistance index were significantly increased in the 19C group (15%, 56%, and 78%, respectively) compared to the 7S group. Bone measurements of the 19S and 19C groups showed a higher femur mass (25%) and a higher lumbar vertebrae mass (11%) and length (5%). Computed tomography analysis revealed more radiodensity in the proximal femoral epiphysis and lumbar vertebrae of 19C group compared to the 7S and 19S groups.

CONCLUSIONS:

Our results suggest that the amount and source of fat used in the diet after weaning increase body growth and fat depots and affect insulin resistance and, consequently, bone health.     

母代高脂饮食对雄性后代小鼠青春期后期运动能力及学习记忆行为的影响

目的:研究母代高脂饮食(high-fat diet,HFD)对雄性后代小鼠青春期后期运动能力及学习记忆行为的影响及机制.方法:通过16周高脂饮食喂养母鼠直至哺乳期结束建立母鼠肥胖模型,以子代雄鼠作为主要研究对象.通过足迹分析和转棒实验研究了子代小鼠的运动协调性,通过旷场实验研究了雄性子代小鼠运动能力的变化,通过水迷宫和...     

podocin和nephrin在高脂饮食C57BL/6J幼鼠肾小球中的表达及意义

目的探讨高脂饮食对幼鼠肾小球裂孔膜蛋白podocin和nephrin表达的影响及意义。方法 36只3周龄雄性C57BL/6J幼鼠随机分为正常饮食组和高脂饮食组,分别给予标准饲料与高脂饲料喂养12周。通过HE和PAS染色观察小鼠肾小球结构的变化;通过免疫组化和免疫印迹技术检测podocin和nephrin蛋白在小鼠肾小球中的表达变化。结果高脂饮食组小鼠出现了肾小囊狭窄以及系膜基质轻度增生等病理改变,且高脂饮食组小鼠肾小球中podocin和nephrin蛋白的表达水平较正常饮食组均显著下调。结论高脂饮食导致裂孔膜蛋白podocin和nephrin低表达,可能是诱发肾小球损伤的原因之一。     

高脂诱导肥胖小鼠视网膜变性的形态学改变

目的 探讨高脂饮食建立的C57BL/6小鼠肥胖模型的视网膜变性的超微结构改变.方法 高脂饲料喂养19周后,小鼠分为肥胖抵抗(DIO-R)组和肥胖倾向(DIO)组,同时对照组小鼠给予基础饲料喂养.应用光镜,透射电镜及TUNEL法检测三组小鼠视网膜超微结构的改变及凋亡情况.结果 与对照组及DIO-R组比较,DIO组小鼠视网...     

Decreased irisin secretion contributes to muscle insulin resistance in high-fat diet mice

Aims: Recent studies have revealed the relationship between irisin and insulin signaling, while positive associations of muscle FNDC5 with insulin resistance is observed. However, the functional mechanism of irisin on muscle insulin resistance is still obscure. This study aims to investigate the effect of irisin on muscle insulin action. Methods: Diabetic mouse model was established by high fat diet (HFD) induced obesity in C57BL/6 mice. Body indexes and serum levels of triglyceride (TG), blood glucose and insulin were record. Oral glucose tolerance test (OGTT) was performed before being killed. Circulating irisin level was also detected, while FNDC5/irisin expression was determined by RT-PCR and western blot analysis in both muscle and adipose tissues. Insulin action was further evaluated by the phosphorylation of AKT and Erk, and palmitic acid treated muscle cells were introduced for mimicking diabetic status in vitro. Results: Obvious obese feathers associated with type 2 diabetes were observed in HFD feeding mice, with decreased circulating irisin level and FNDC5/irisin secretion in adipose tissues. Although FNDC5/irisin expression showed little change in skeletal muscle, the insulin action was inhibited significantly. Moreover, palmitic acid treated muscle cells showed similar inhibition of insulin action, and FNDC5/irisin expression change. Besides, insulin action could be reversed by irisin addition in muscle cells. Conclusion: HFD induced obese mice showed decreased irisin secretion from adipose tissues, which might contribute to muscle insulin resistance. Furthermore, irisin addition could recover insulin action in palmitic acid treated muscle cells, indicating the importance of irisin for preserving insulin signaling.