促红细胞生成素导致肥胖小鼠棕色脂肪PPAR γ、UCP1和β3-AR的表达变化

目的观察注射促红细胞生成素(Erythropoietin,EPO)后,高脂喂养(high fat diet,HFD)的肥胖小鼠模型体重、脂肪含量变化以及白色脂肪组织、棕色脂肪组织中过氧化物酶体增殖激活受体γ(peroxisome proliferator-activated receptorγ,PPAR γ)、解偶联蛋白1(uncoupling protein 1,UCP1)、β3肾上腺素能受体(β3 adrenoceptor,β3-AR)mRNA以及蛋白的表达变化,为EPO治疗肥胖的机制提供线索。方法 20只高脂喂养的C57BL/6J雄鼠随机分为对照组(HFD-Con)和EPO组(HFD-EPO)。4周后比较两组动物的体重,实时定量PCR方法检测皮下脂肪、附睾脂肪以及棕色脂肪中的PPAR γ、UCP1和β3-AR mRNA表达变化。结果 4周后,与对照组比较,EPO组体重(24.53±2.03)g,HFD-Con组体重为(31.78±1.68)g,P0.001。HFD-EPO组动物的皮下脂肪与附睾脂肪重量均显著减少,P0.001。HE染色结果显示,相较于HFD-Con组,HFD-EPO组动物的脂肪细胞减小。半定量PCR和Western blotting结果显示,皮下脂肪组织与附睾脂肪组织中的PPAR γ、UCP1、β3-AR mRNA以及蛋白的表达均无显著性改变,而棕色脂肪中的PPAR γ、UCP1、β3-AR的mRNA以及蛋白表达均显著增加。结论棕色脂肪中PPAR γ、UCP1、β3-AR表达变化可能与高脂喂养后注射EPO导致体重减轻存在一定的联系。     

小檗碱降低高脂模型大鼠血脂及可能机制

目的研究小檗碱(BBr)对高脂模型大鼠血脂的影响及其可能机制。方法采用灌胃脂肪乳剂一个月的大鼠为高脂动物模型。实验分组:正常对照组;(B)模型组;(C)非诺贝特组(100mg/kg灌胃);(D)小檗碱低剂量组(50mg/kg);(E)小檗碱中剂量组(100mg/kg);(F)小檗碱高剂量组(200mg/kg);(G)小檗碱注射组(3mg/kg)。全自动生化分析检测各组大鼠血脂变化;Western-blot检测各组大鼠肝脏PPARα、骨骼肌PPARδ和脂肪组织PPARγ水平;Western blot及RT-PCR技术检测大鼠小肠载脂蛋白apoB以及脂酰COA合成酶的表达变化。结果与模型组比较,3个剂量小檗碱口服组及小檗碱注射组大鼠血清总胆固醇(TC)以及甘油三酯(TG)水平明显下降,高密度脂蛋白胆固醇(HDL-C)和载脂蛋白AI(Apo AI)水平则明显上升。与模型组比较,非诺贝特组、小檗碱三个剂量口服组和小檗碱注射组大鼠肝组织PPARα表达水平明显上调,而骨骼肌PPARδ和脂肪组织PPARγ表达水平无明显差异。小檗碱中、高剂量灌胃组大鼠小肠脂酰CoA合成酶m RNA水平较模型组显著下降。结论小檗碱降低大鼠高血脂作用可能与降低脂代谢相关因子载脂蛋白apoB以及脂酰COA合成酶含量相关。     

单纯性肥胖大鼠的肥胖特点及瘦素的变化

目的:在单纯性肥胖大鼠中研究其肥胖特点及瘦素的变化。方法:60只新生SD大鼠随机分成两组,肥胖组(n=40)喂高能量饲料,对照组(n=20)喂普通饲料,动态观察体重、腹腔脂肪的变化,用免疫组化(ABC法)法观察腹腔脂肪细胞瘦素表达,用放免法测血清瘦素水平。结果:肥胖组大鼠与非肥胖对照组大鼠比,第7周体重增长最显,12周内体重持续上升,12周时腹腔脂肪重量增加,脂肪细胞增大,脂肪细胞瘦素表达增强,且与腹腔脂肪组织重量呈明显正相关,肥胖大鼠血清瘦素水平明显低于对照组(P＜0.05)。结论:在单纯性肥胖大鼠中体重、Lee's指数、腹腔脂肪重量、脂肪细胞大小变化显著。肥胖鼠的脂肪细胞瘦素表达增强,并与腹腔脂肪重量呈正相关,因此它可作为衡量大鼠肥胖程度的一项指标。     

低脂饮食和有氧运动干预对高脂大鼠脂肪组织蛋白激酶B表达的影响

目的 :观察低脂饮食和有氧运动对高脂大鼠脂肪组织中蛋白激酶B(PKB)表达的影响。方法 :选取雄性Wistar大鼠 4 0只 ,随机分为正常对照组 ( 10只 )和模型组 ( 30只 )。模型组大鼠给予高脂喂养 ,4周后 ,再随机分为 3组 :胰岛素抵抗组 ,继续高脂饮食 ;低脂饮食组 ,给予低脂饮食 ;有氧运动组 ,继续高脂饮食 +有氧运动。干预 6周后 ,蛋白印迹法检测大鼠脂肪组织中胰岛素刺激PKB表达的含量变化。结果 :低脂饮食组和有氧运动组大鼠空腹血糖 (FBG)、甘油三酯 (TG)、胆固醇 (TC)、内脏脂肪及胰岛素抵抗指数 (HOMA IR)下降 ,胰岛素敏感指数 (ISI)显著升高。而PKB蛋白表达分别增加了 16 .1%和 19.2 %(P <0 .0 1)。结论 :低脂饮食和有氧运动能改善胰岛素抵抗 ,可能与增加脂肪组织中PKB蛋白表达有关。     

妊娠期高脂饮食对子代大鼠成年期肥胖影响的研究

目的 观察、分析母鼠妊娠期高脂饮食对子代成年期肥胖的影响.方法 24只健康的雌性Wistar大鼠,经确认怀孕便随机分为普食组(basic diet B)和高脂组(hish-fat diet HF),分别用基础饲料和高脂饲料喂养妊娠期及哺乳期.断奶后,将妊娠期高脂喂养组的雄性子代随机分为普食组和高脂组,分别用基础饲料和高脂饲料喂养12周.测量各子代大鼠体重、体长变化、肠系膜及肾周脂肪垫重量、血清Leptin值和血清脂质(TC、TG、HDL-C和LDL-C)水平,计算Lee's指数.结果 (1)体重、Lee's指数亲代高脂子代普食(HF/B)组该值为三组中最低.(2)肠系膜及肾周脂肪垫重量三组间无显著性差异.(3)血清脂质TG、HDL-C出生后继续高脂饲养组(HF/HF)的TG值均高于继续普食喂养组(B/B、HWB).B/B与HF/B间HDL-C无差异,但均高于HF/HF组;TC、LDL-C HF/HF的TC、LDL-C值在三组中均为最高,继续普食喂养的两组中,HF/B组也高于B/B组.(4)血清Leptin值HF/HF高于B/B、HF/B.结论 妊娠期高脂饮食会影响子代成年期血脂代谢及肥胖发生,出生后饮食调节可减弱其影响作用.     

高脂饮食诱发血糖升高的动物模型中瘦素与胰岛素变化的关系

高脂饲料喂养大鼠,诱发胰岛素抵抗形成血糖升高,以研究瘦素与糖尿病的关系。将大鼠分为正常和高脂饲料喂养组,于喂养前及喂养30、60d时测血糖、瘦素与胰岛素水平,行高胰岛素正常血糖钳夹试验,最后分离分离脂肪称重。结果：高脂饮食组具有明显的胰岛素抵抗,有50％血糖升至8．3mmol/L以上;形成糖尿病的大鼠体重与对照组无明显区别;高脂饮食组瘦素与胰岛素水平与对照组比较有明显差异;所有大鼠瘦素水平与体重、胰岛素、血糖均呈正相关。结论：（1）高脂饮食是导致胰岛素抵抗形成糖尿病的诱因之一;（2）体脂含量与糖尿病正相关;（3）瘦素抵抗与胰岛素抵抗形成糖尿病的发病机制可能有关;（4）瘦素水平随着鼠龄的增加而增高,且参与体重的调节。     

茜草水溶性提取物减少高脂饮食诱导的肥胖大鼠内脏脂肪

目的探究传统中药茜草水溶性提取物(RCAE)对高脂饮食诱导的肥胖大鼠体质量、脂肪含量及糖脂代谢指标的影响及机制。方法构建含PPARγ2启动子序列的p GL3-Enhancer-PPARγ2(625 bp)-Luc荧光素酶报告基因表达质粒;建立稳定转染该质粒的3T3-L1前脂肪细胞系;用不同浓度(0.1 mg/L~1 000 mg/L)水提法提取的RCAE作用该细胞或用100 mg/L RCAE作用不同时间,检测PPARγ2启动子活性;用100 mg/L RCAE刺激人脂肪细胞并检测PPARγ2 mRNA表达;同时高脂饮食喂养大鼠,观察小和大剂量RCAE干预对血糖、血脂、胰岛素水平、体质量和内脏脂肪质量等的影响。结果 10 mg/L RCAE能促进3T3-L1细胞荧光素酶的表达,是对照组的1.43倍(P0.01);当浓度达1 000 mg/L时,荧光素酶活性增加至对照组的3.24倍(P0.01)。100 mg/L RCAE刺激3T3-L1细胞28 h,荧光素酶活性达最大值,是对照组的2.72倍(P0.01);还能显著促进人脂肪细胞中PPARγ2 mRNA的表达,是对照组的2.27倍(P0.01)。与高脂对照组相比,小剂量茜草组的空腹胰岛素水平及HOMA-IR显著降低,内脏脂肪质量明显减少(P0.05)。结论小剂量RCAE能显著减轻高脂饮食诱导的肥胖大鼠的内脏脂肪质量和改善胰岛素抵抗。其作用机制可能与增强PPARγ2基因启动子活性和促进PPARγ2 mRNA表达有关。     

罗格列酮抑制非酒精性脂肪性肝炎大鼠肝组织IKK-β的表达

目的探讨罗格列酮对非酒精性脂肪性肝炎(NASH)大鼠肝组织中IκB激酶β(IKK-β)表达的影响及意义。方法健康雄性Wistar大鼠高脂饲料喂养16周建立NASH模型,应用不同剂量罗格列酮灌胃治疗,并继续高脂饲料喂养12周后空腹收集大鼠血清及肝组织,ELISA检测血清TNF-α水平,RT-PCR和免疫组化染色观察大鼠肝组织IKK-βmRNA、蛋白的表达。结果模型组大鼠血清TNF-α水平显著增高,肝组织IKK-βmRNA及蛋白表达明显增强(P<0.01),肝组织有不同程度的脂肪变性、炎症坏死和纤维化。罗格列酮治疗组上述变化显著缓解,且与罗格列酮剂量正相关。结论罗格列酮可以阻止NASH大鼠IKK-β的表达和TNF-α的生成,抑制肝脏炎症反应。     

组蛋白去甲基化酶抑制剂GSK-J4减轻高脂诱导的肥胖小鼠体质量

目的 研究组蛋白去甲基化酶抑制剂GSK-J4如何降低高脂诱导的肥胖小鼠体质量。方法 使用高脂饲料(HFD)喂养C57/BL6小鼠16周后，连续腹腔注射GSK-J4 16 d,在此期间监测小鼠体质量和体温。ELISA试剂盒检测血清瘦素的表达。流式细胞测量术检测附睾和皮下脂肪组织中巨噬细胞的极化方向。HE染色和免疫组化的评价附睾脂肪组织和皮下脂肪组织中白色脂肪棕色化程度。RT-qPCR分析巨噬细胞中相关细胞因子和氧化磷酸化相关基因的表达水平。结果 与溶剂对照组相比，GSK-J4时间依赖性降低小鼠体质量；显著降低血清中瘦素表达水平(P<0.01);减少附睾和皮下脂肪组织巨噬细胞的表面标志物CD11c⁺减少；增加皮下白色脂肪棕色化程度；刺激棕色脂肪组织中氧化磷酸化相关基因mRNA水平表达，降低IL-1β表达水平。结论 组蛋白去甲基化酶抑制剂GSK-J4可以减少巨噬细胞的M1极化。GSK-J4处理小鼠后可显著降低HFD所致肥胖小鼠的体质量，增加能量消耗。     

山荷减肥颗粒对饮食诱导肥胖大鼠瘦素、脂联素、抵抗素的影响

目的： 观察山荷减肥颗粒对高脂饮食诱导的肥胖模型大鼠的减肥降脂作用及对脂肪组织脂联素、抵抗素基因表达的影响。方法： 肥胖模型大鼠随机分为山荷减肥颗粒高、中、低剂量3个实验组及高脂对照组、正常组。对给药8周的动物称体重,测体长,计算Lees指数,测定大鼠血清胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白（LDL）及高密度脂蛋白（HDL）的水平,用ELISA法测瘦素水平,用RT-PCR 检测附睾周围脂肪组织脂联素、抵抗素mRNA 表达。结果：山荷减肥颗粒组大鼠体重、Lees指数、脂肪重量、血清TC、TG、LDL水平明显低于高脂组大鼠（P<0.05）,瘦素明显低于高脂模型组（P>0.05）,脂肪组织脂联素、抵抗素mRNA的表达水平明显高于高脂组大鼠（P<0.05）。结论：山荷减肥颗粒对肥胖大鼠具有减肥降脂作用,调整肥胖大鼠脂肪组织瘦素、脂联素、抵抗素mRNA的表达水平,可能是其治疗肥胖的作用机制之一。     

Pain and Effusion and Quadriceps Activation and Strength

Context:

Quadriceps dysfunction is a common consequence of knee joint injury and disease, yet its causes remain elusive.

Objective:

To determine the effects of pain on quadriceps strength and activation and to learn if simultaneous pain and knee joint effusion affect the magnitude of quadriceps dysfunction.

Design:

Crossover study.

Setting:

University research laboratory.

Patients or Other Participants:

Fourteen (8 men, 6 women; age = 23.6 ± 4.8 years, height = 170.3 ± 9.16 cm, mass = 72.9 ± 11.84 kg) healthy volunteers.

Intervention(s):

All participants were tested under 4 randomized conditions: normal knee, effused knee, painful knee, and effused and painful knee.

Main Outcome Measure(s):

Quadriceps strength (Nm/kg) and activation (central activation ratio) were assessed after each condition was induced.

Results:

Quadriceps strength and activation were highest under the normal knee condition and differed from the 3 experimental knee conditions (P < .05). No differences were noted among the 3 experimental knee conditions for either variable (P > .05).

Conclusions:

Both pain and effusion led to quadriceps dysfunction, but the interaction of the 2 stimuli did not increase the magnitude of the strength or activation deficits. Therefore, pain and effusion can be considered equally potent in eliciting quadriceps inhibition. Given that pain and effusion accompany numerous knee conditions, the prevalence of quadriceps dysfunction is likely high.Key Words: arthrogenic muscle inhibition, central activation failure, voluntary activation, muscles

Key Points

• Knee pain and effusion resulted in arthrogenic muscle inhibition and weakness of the quadriceps.
• The simultaneous presence of pain and effusion did not increase the magnitude of quadriceps dysfunction.
• To reduce arthrogenic muscle inhibition and improve muscle strength, clinicians should employ interventions that target removing both pain and effusion.

Quadriceps weakness is a common consequence of traumatic knee joint injury^1,2 and chronic degenerative knee joint conditions.^3,4 Arthrogenic muscle inhibition (AMI), a neurologic decline in muscle activation, results in quadriceps weakness and hinders rehabilitation by preventing gains in strength.⁵ The inability to reverse AMI and restore muscle function can lead to decreased physical abilities,⁶ biomechanical deficits,⁷ and possibly reinjury.⁵ Furthermore, researchers^8,9 have suggested that quadriceps weakness resulting from AMI may place patients at risk for developing osteoarthritis in the knee. In light of the substantial influence of quadriceps AMI on these clinically relevant outcomes, we need to improve our understanding of the factors that contribute to this neurologic decline in muscle activity so efforts to target and reverse it can be implemented and gains in strength can be achieved more easily.Joint injury and disease are accompanied by numerous sequelae (ie, pain, swelling, tissue damage, inflammation), so ascertaining which one ultimately leads to neurologic muscle dysfunction is difficult. Whereas a joint effusion can result in AMI,^10–12 the effects of pain are less understood despite many clinicians attributing AMI to pain. Using techniques that introduce knee pain without accompanying injury may provide insights into the role of pain in eliciting AMI.The degree of knee joint damage may play a role in the quantity of AMI that manifests. Hurley et al^13,14 demonstrated that quadriceps AMI, measured using an interpolated-twitch technique, was greater in patients with extensive traumatic knee injury (eg, fractured tibial plateau, ruptured medial collateral ligament, and medial meniscectomy) than patients with isolated joint trauma (ie, isolated anterior cruciate ligament [ACL] rupture). Similarly, patients with more knee joint symptoms (ie, greater number of symptoms and increased severity of symptoms) may present with greater magnitudes of quadriceps inhibition. Recently, investigators¹⁵ have suggested that patients with more pain display less quadriceps strength, supporting this tenet. Given that effusion and pain often present simultaneously with joint injuries and diseases, such as ACL injury and osteoarthritis, examining both the isolated and cumulative effects of these sequelae appears warranted to determine if they influence the magnitude of muscle inhibition.Experimental joint-effusion and pain models are safe and effective experimental methods that allow for the isolated examination of their effects on muscle function. The effusion model, whereby sterile saline is injected directly into the knee joint capsule,⁷ produces a clinically relevant magnitude of the joint effusion that may be present with traumatic injury. Effusion is thought to activate group II afferents responding to stretch or pressure,^16–18 which in turn may facilitate group Ib interneurons and result in quadriceps AMI.⁵ The pain model involves injecting hypertonic saline into the infrapatellar fat pad to produce anteromedial knee pain similar to that described in patients with patellofemoral pain syndrome.¹⁹ Pain is considered to initiate AMI through activation of group III and IV afferents that act as nocioceptors to signal damage or potential damage to joint structures.^16–18 The firing of these afferents then may lead to facilitation of group Ib interneurons, the flexion reflex, or the gamma loop, ultimately resulting in quadriceps inhibition.²⁰ Thus, these models allow us to create symptoms that are associated with knee injury and have the added benefit of providing a way to examine their effects in isolation.Therefore, the purpose of our study was to determine the effects of pain on quadriceps strength and activation and to learn if simultaneous pain and knee joint effusion would affect the magnitude of quadriceps dysfunction. We hypothesized that pain alone would result in quadriceps inhibition and that the magnitude of inhibition would be greater when effusion and pain were present simultaneously.     

即早基因c-fos与脑血管病及学习记忆

即早基因c-fos是广泛存在于原核细胞和真核细胞的高度保守基因.在正常情况下,c-fos基因参与细胞生长、分化、信息传递、学习和记忆等生理过程,而在病理情况下c-fos基因表达及调控变化与多种疾病的发生和发展有关.C-fos在中枢神经系统的某些部位可有基础水平的表达,但表达很低,当受到如脑缺血、脑出血、痫性发作、应激等刺激后,其在数十分钟内做出反应,在对外界刺激-转录耦联的信忠传递过程中起着核内第三信使的重要作用.     

Opportunities and challenges in the prevention and control of cancer and other chronic diseases: children's diet and nutrition and weight and physical activity

OBJECTIVE: The purpose of this article is to review the role of behavioral research in disease prevention and control, with a particular emphasis on lifestyle- and behavior-related cancer and chronic disease risk factors--specifically, relationships among diet and nutrition and weight and physical activity with adult cancer, and tracking developmental origins of these health-promoting and health-compromising behaviors from childhood into adulthood. METHOD: After reviewing the background of the field of cancer prevention and control and establishing plausibility for the role of child health behavior in adult cancer risk, studies selected from the pediatric published literature are reviewed. Articles were retrieved, selected, and summarized to illustrate that results from separate but related fields of study are combinable to yield insights into the prevention and control of cancer and other chronic diseases in adulthood through the conduct of nonintervention and intervention research with children in clinical, public health, and other contexts. RESULTS: As illustrated by the evidence presented in this review, there are numerous reasons (biological, psychological, and social), opportunities (school and community, health care, and family settings), and approaches (nonintervention and intervention) to understand and impact behavior change in children's diet and nutrition and weight and physical activity. CONCLUSIONS: Further development and evaluation of behavioral science intervention protocols conducted with children are necessary to understand the efficacy of these approaches and their public health impact on proximal and distal cancer, cancer-related, and chronic disease outcomes before diffusion. It is clear that more attention should be paid to early life and early developmental phases in cancer prevention.