骨组织雌激素受体及其应用的研究进展

绝经和年龄增长是妇女骨量丢失的两个重要因素，骨组织通过破骨与成骨的偶联活动而自我更新和重建。破骨细胞吸收旧骨，然后成骨细胞形成新骨，完成一次骨转换。如果新骨不能填满旧骨被吸收后留下的空隙，则骨代谢出现负平衡，骨量减少。雌激素不足与骨转换增加及骨量丢失加速有关，是     

雌激素在I型原发性骨质疏松症发病机制中作用的研究进展

Ｉ型骨质疏松症即绝经后骨质疏松症（Ｐｏｓｔｍｅｎｏｐａｕｓａｌｏｓｔｅｏｐｏｒｏｓｉｓ,ＰＭＯ）是指绝经后妇女由于体内卵巢功能低下,雌激素明显减少,骨偶联过程失衡,破骨细胞性骨吸收作用超过了成骨细胞性骨形成作用,所导致的净骨量减少,骨强度降低,骨脆性...     

雌激素与雌激素受体骨代谢调节作用

雌激素缺乏是绝经后骨质疏松症发生的主要原因,雌激素或雌激素受体调节剂与雌激素受体结合后通过多种分子生物学机制,抑制破骨细胞骨吸收,促进成骨细胞骨形成、提高骨密度,达到治疗绝经后骨质疏松症的目的。本文综述了雌激素、选择性雌激素受体调节剂与雌激素受体相互作用对骨代谢的调节机制、雌激素治疗骨质疏松症的动物实验研究以及雌激素治疗骨质疏松症的临床研究进展,旨在为临床骨质疏松治疗策略提供科学依据。     

IL-1与骨质疏松研究进展

骨质疏松症已经成为与衰老相关的最重要的疾病之一。女性发生率高的原因是由于绝经后雌激素水平的降低伴有骨吸收的增加。最新的研究显示,免疫系统可能是参与绝经后骨质疏松的重要因素,作用于成骨细胞及破骨细胞的促炎因子,以及免疫系统的激活被认为是引起骨质疏松的危险因素,其中白介素-1(IL-1)作为强有力的破骨细胞刺激因子,在生理状态下以及炎症性疾病、绝经后全身性骨量丢失中均发挥着重要作用。本文就IL-1家族、IL-1在细胞、信号通路、动物模型等方面的文献进行回顾,并就IL-1抑制剂、拮抗剂及其衍生物对骨代谢作用进行综述。     

细胞因子在绝经后骨质疏松症发病机制中的作用

雌激素、免疫细胞因子及骨代谢三者相互作用,绝经后骨质疏松症主要与雌激素缺乏导致细胞因子激活破骨细胞的活性密切相关。雌激素缺乏导致巨噬细胞和T细胞分泌IL-1和TNFα,抑制调节性T细胞增殖和成熟,促进NFκB、IL-15和IL-17的产生,从而诱导破骨细胞发展;抑制成骨细胞和骨系细胞产生OPG,促进RANK-RANKL相互作用,导致破骨细胞活性增强;抑制成骨细胞和骨细胞的TGFβ,减少破骨细胞凋亡。     

骨免疫与绝经后骨质疏松妇女骨重建失衡

绝经后骨质疏松是因雌激素水平下降引起骨免疫功能增强,导致骨重建失衡所致。成骨细胞和破骨细胞相互作用是调控骨重建的核心因素,而RANKL/RANK/OPG系统是连接骨与免疫系统之间的分子桥梁,在调节骨吸收和骨形成耦联中发挥关键作用。骨细胞和免疫细胞通过共同的细胞因子及受体相互作用,调节骨代谢平衡,以共同的骨代谢转录因子和信号分子调控骨重建过程。雌激素作为骨细胞与免疫细胞的共同交叉机制,通过经典性激素受体途径调控T细胞活化,介导免疫因子的产生和表达,影响免疫细胞、成骨细胞、破骨细胞的活性和功能,既有正性调节作用,又有负性调节作用,决定骨重建方向。因此,骨免疫在调控绝经后骨质疏松症骨重建失衡中发挥重要作用。补肾法是中医药治疗绝经后骨质疏松症的根本治则,长期临床应用疗效显著,其作用机制可能是通过干预骨免疫而调节骨重建失衡,为治疗绝经后骨质疏松症提供新的切入点。     

绝经后骨质疏松的骨免疫学机制

绝经后骨质疏松是雌激素缺乏引起骨形成与骨吸收解耦联,导致骨吸收大于骨形成,进而引起骨量减少,一般表现为骨密度的降低及骨微结构的破坏,最终骨脆性增加易于骨折。随着我国社会经济的发展,人口老龄化日益增加,绝经后骨质疏松的患病率也日趋上升,给患者家庭及社会医疗带来了极大的挑战。绝经后骨质疏松被认为是一种慢性低度炎症的全身性疾病。雌激素缺乏使得B细胞及T细胞被激活,激活的淋巴细胞分泌TNF-α、IL-17、IL-6及RANKL等促骨吸收因子促进破骨细胞骨吸收。目前认为雌激素缺乏导致的骨丢失与趋化因子、免疫细胞及其分泌的细胞因子密切相关,即绝经后骨质疏松的骨免疫学机制。     

绝经后骨质疏松症的骨微环境改变探析

绝经后雌激素低落引起的成骨细胞、破骨细胞、骨细胞异常凋亡,导致骨形成、骨吸收脱偶联,是绝经后骨质疏松症发生的重要原因,由于雌激素的缺乏破坏了其对骨局部细胞因子、生长因子、体液因子的调控,骨微环境改变,刺激骨吸收大于骨形成,本文就绝经后骨质疏松症的骨微环境改变作一理论探析,为临床治疗拓展新途径.     

雌激素在Ⅰ型原发性骨质疏松症发病机制中作用的研究进展

Ⅰ型骨质疏松症即绝经后骨质疏松症(Postmenopausal osteoporosis，PMO)是指绝经后妇女由于体内卵巢功能低下，雌激素明显减少，骨偶联过程失衡，破骨细胞性骨吸收作用超过了成骨细胞性骨形成作用，所导致的净骨量减少，骨强度降低，骨脆性增加的代谢性骨疾病。1940年Albright首先提出PMO的发生与体内雌激素减少有关，并首倡应用雌激素治疗。至今此疗法仍被应用，足以证明，雌激素防治骨质疏松症的有效性。现已证实，雌激素对骨代谢发挥了重要的保护作用，其中维持骨偶联平衡的作用尤为突出。现就其在PMO发病机制的作用，做一文献复习。     

Fas/Fas-L信号系统在绝经后骨质疏松症中作用的研究进展

Fas/Fas-L信号系统是外源性凋亡通路的重要组成部分。近年来大量研究发现,Fas/Fas-L信号系统通过诱导细胞凋亡,不仅参与了免疫系统稳态的维持,而且在骨内环境稳态的调节中也发挥了重要的作用。Fas/Fas-L信号系统在不同骨细胞上的表达和分布可能随体内雌激素水平波动而发生变化。当绝经后雌激素分泌不足时,Fas/Fas-L信号系统可通过启动骨细胞外源性凋亡通路,介导成骨和破骨平衡向破骨方向偏移,参与绝经后骨质疏松症的发生发展。通过调节骨细胞上Fas/Fas-L信号系统来平衡破骨细胞骨吸收和成骨细胞骨形成,将为绝经后骨质疏松症的治疗提供新的思路。     

长春瑞滨化疗性静脉炎动物模型的建立

目的探讨建立长春瑞滨化疗性静脉炎动物模型适宜的给药浓度,为化疗性静脉炎的发生机制研究提供实验基础。方法选择实验用健康家兔28只,采用随机数字表法分为四组各7只。均于一侧耳缘静脉注药建模。第1组注射生理盐水10mL作为阴性对照,其余3组将长春瑞滨用10mL生理盐水溶解,分别按12.5mg/m2、25mg/m2和50mg/m2剂量注射。结果长春瑞滨组静脉炎症反应出现于注射后24h,48h左右表现最显著,约于1周恢复。25mg/m2组、50mg/m2组注射后48h有典型的静脉炎病理变化,50mg/m2组4只家兔分别于药物注射后第7～10天死亡,25mg/m2组家兔无死亡。结论参照人体用量采用长春瑞滨25mg/m2于家兔耳缘静脉化疗,能较好建立化疗性静脉炎动物模型。     

大鼠烫伤创面感染模型的研制

Objective To reproduce a reliable rat model of burn with infection for the study of prevention and treatment of infected wound. Methods ( 1 ) Electrical burn producing apparatus equipped with constant temperature (80 ℃ ) and pressure (0.5 kg) was used to reproduce burn injury (with area of 4.5 cm2 ) on both sides of the back in 50 SD rats for different duration (4, 6, 8, 10, 12 s) , with 10 rats for each burn duration. On post burn day (PBD) 1, gross condition of wounds was observed with naked eyes.Wounds on the left side were used to observe healing time. The wounds on the right side were used for histological observation to determine the depth of injury, and they were classified into superficial and deep partialthickness injury. (2) Another 36 SD rats were divided into A (inflicted with superficial partial-thickness burn, n = 18) and B (inflicted with deep partial-thickness burn, n = 18) groups according to the random number table. Rats in both groups were treated in accordance with method of preliminary experiment. Immediately after burn, 0. 1 mL of liquid containing 1 × 109, 1 × 107, 1 × 105 CFU Pseudomonas aeruginosa (PA) ATCC 27853 was respectively inoculated to the wounds on one side (with 6 rats for each amount) ,while the wounds on the other side were treated with the same volume of normal saline as control. Inflammatory reaction of wounds was examined with HE staining on post inoculation day (PID) 1. On PID 1, 2, 3,5, 7, and 14, the number of subeschar bacteria was respectively counted and the bacteria were identified with Gram stain and biochemical reaction. Wound healing time was recorded. Data were processed with t test. Results (1) Burn for 6, 8 s was respectively identified as injury time resulting in superficial or deep partial-thickness injury according to histological observation and wound healing time. (2) Obvious inflammatory cell infiltration was observed in the wounds in B group which were inoculated with 1 × 107 , 1 ×109 CFU PA, and the infiltration was less marked in A group with inoculation of 1 × 109 CFU PA. (3) The bacteria isolated from wounds of A and B groups was identified as PA. The subeschar bacteria count within PID 14 in A group, in which different amount of PA was inoculated, was mostly less than 1 × 105 CFU/g of tissue, while that in B group in which 1 × 109 CFU PA was inoculated was more than 1 × 105 CFU/g of tissue. (4) There was no obvious difference in wound healing time between wounds inoculated with different amount of PA and wounds treated with normal saline in A group ( with t value respectively 1.26, 0. 29, 1.07,P values all above 0.05 ). Wound healing time of wounds in B group, in which 1 × 109 CFU PA was inoculated, was longer as compared with that treated with normal saline [(22.5 + 1.0) d vs. ( 19.4 + 1.6) d, t =2.73, P ＜0. 05]. Conclusions In rat, deep partial-thickness burn wound inoculated with 1 × 109 CFU PA ATCC 27853 is a reliable model with high reproducibility for the study of infection of burn wound.     

大鼠烫伤创面感染模型的研制

Objective To reproduce a reliable rat model of burn with infection for the study of prevention and treatment of infected wound. Methods ( 1 ) Electrical burn producing apparatus equipped with constant temperature (80 ℃ ) and pressure (0.5 kg) was used to reproduce burn injury (with area of 4.5 cm2 ) on both sides of the back in 50 SD rats for different duration (4, 6, 8, 10, 12 s) , with 10 rats for each burn duration. On post burn day (PBD) 1, gross condition of wounds was observed with naked eyes.Wounds on the left side were used to observe healing time. The wounds on the right side were used for histological observation to determine the depth of injury, and they were classified into superficial and deep partialthickness injury. (2) Another 36 SD rats were divided into A (inflicted with superficial partial-thickness burn, n = 18) and B (inflicted with deep partial-thickness burn, n = 18) groups according to the random number table. Rats in both groups were treated in accordance with method of preliminary experiment. Immediately after burn, 0. 1 mL of liquid containing 1 × 109, 1 × 107, 1 × 105 CFU Pseudomonas aeruginosa (PA) ATCC 27853 was respectively inoculated to the wounds on one side (with 6 rats for each amount) ,while the wounds on the other side were treated with the same volume of normal saline as control. Inflammatory reaction of wounds was examined with HE staining on post inoculation day (PID) 1. On PID 1, 2, 3,5, 7, and 14, the number of subeschar bacteria was respectively counted and the bacteria were identified with Gram stain and biochemical reaction. Wound healing time was recorded. Data were processed with t test. Results (1) Burn for 6, 8 s was respectively identified as injury time resulting in superficial or deep partial-thickness injury according to histological observation and wound healing time. (2) Obvious inflammatory cell infiltration was observed in the wounds in B group which were inoculated with 1 × 107 , 1 ×109 CFU PA, and the infiltration was less marked in A group with inoculation of 1 × 109 CFU PA. (3) The bacteria isolated from wounds of A and B groups was identified as PA. The subeschar bacteria count within PID 14 in A group, in which different amount of PA was inoculated, was mostly less than 1 × 105 CFU/g of tissue, while that in B group in which 1 × 109 CFU PA was inoculated was more than 1 × 105 CFU/g of tissue. (4) There was no obvious difference in wound healing time between wounds inoculated with different amount of PA and wounds treated with normal saline in A group ( with t value respectively 1.26, 0. 29, 1.07,P values all above 0.05 ). Wound healing time of wounds in B group, in which 1 × 109 CFU PA was inoculated, was longer as compared with that treated with normal saline [(22.5 + 1.0) d vs. ( 19.4 + 1.6) d, t =2.73, P ＜0. 05]. Conclusions In rat, deep partial-thickness burn wound inoculated with 1 × 109 CFU PA ATCC 27853 is a reliable model with high reproducibility for the study of infection of burn wound.     

Benefits and limitations of animal models in partial bladder outlet obstruction for translational research

The functions of the lower urinary tract have been investigated for more than a century. Lower urinary tract symptoms, such as incomplete bladder emptying, weak urine stream, daytime urinary frequency, urgency, urge incontinence and nocturia after partial bladder outlet obstruction, is a frequent cause of benign prostatic hyperplasia in aging men. However, the pathophysiological mechanisms have not been fully elucidated. The use of animal models is absolutely imperative for understanding the pathophysiological processes involved in bladder dysfunction. Surgical induction has been used to study lower urinary tract functions of numerous animal species, such as pig, dog, rabbit, guinea pig, rat and mouse, of both sexes. Several morphological and functional modifications under partial bladder outlet obstruction have not only been observed in the bladder, but also in the central nervous system. Understanding the changes of the lower urinary tract functions induced by partial bladder outlet obstruction would also contribute to appropriate drug development for treating these pathophysiological conditions. In the present review, we discuss techniques for creating partial bladder outlet obstruction, the characteristics of several species, as well as issues of each model, and their translational value.     

近十年我国护理学动物实验研究计量实证分析

目的了解我国护理学科动物实验的研究状况和发展趋势,为进一步开展护理学动物实验研究提供参考。方法通过万方数据库、中国知网对《中华护理杂志》、《护理学杂志》等8种期刊2004~2013年十年护理学动物实验研究进行文献检索,并采用文献计量法、内容分析法对资料进行整理分析。结果共检出文献272篇,其中论著99篇;合著率高达98.16%;72.79%为基金论文;总被引频次达1 240次;涉及22个地域,发文量最多的地区是广东省。研究动物有兔、鼠、犬、猪、羊;共涉及8个研究类别、5种实验干预方式、6种实验设计方法。结论动物实验是护理学的重要研究方法 ,但近十年来我国护理学动物实验研究呈总体下降趋势。应加大力度开展护理学动物实验研究,提高护理动物学基金项目资助率,扩大研究领域,规范实验设计方法 ,提升研究整体质量,提高研究结果的临床推广价值。     

Advances in the development of experimental composite tissue transplantation models

The preclinical experimental models of composite tissue allograft (CTA) have rapidly developed in the past years. When microsurgical techniques were established, researchers focused on immunomodulatory protocols that overcome the immunologic barrier between the allogenic donor and recipient. To test immunologic response, functional recovery, and technical feasibility, experimental CTA has been performed in different models, including rodents, large animals, and nonhuman primates. In the experimental studies, researchers are focused on tolerance-inducing strategies based on immunosuppressive protocols allowing for widespread application in the clinic. In this review, authors analyzed the current knowledge of immunologic aspects and tolerance-inducing strategies in CTA experimental models, including single components such as skin or vascularized bone allograft versus CTA containing multiple tissues such as experimental limb and face transplants, and emphasized their relevance and applicability to the clinical scenario.     

兔慢性肝损害急性肝衰竭动物模型的建立

Objective To establish an ideal animal model of acute-on-chronic liver failure (ACLF) in New Zealand white rabbits in order to provide a large animal model for further researches.Methods Totally 75 New Zealand rabbits were randomly divided into experimental group (n =70) and control group (n = 5 ). Rabbits in the experimental group were injected with CCl4 into the abdominal cavity twice every week and the doses of CCl4 were modified according to the index of liver function and the body weight, whereas those in the control group were treated with the same volume of saline. At the 10th week,48 New Zealand rabbits with hepatic fibrosis were randomly assigned to 4 groups and injected with CCl4 as before, D-Gal at a dose of 0. 65 g/kg body weight (BW), 0. 70 g/kg BW and 0. 75 g/kg BW, respectively. By observing and comparing the general state, survival time, biochemical indexes, and the histopathology, a method of establishing a stable animal model of acute hepatic failure was found. Results As compared with those in control group, the levels of ALT, AST, GGT, HA, LN and PC-Ⅲ in the experiment group were increased significantly, while the level of ALB was decreased at the end of 10 weeks. Typical features of hepatic fibrosis and the formation of pseudo-lobules were observed at the end of 10 weeks. After treatment with D-Gal, all rabbits in group Ⅰ survived with minimal changes in liver function tests. In group Ⅱ , there was a temporary hepatic injury, but no hepatic coma. Four of the 12 rabbits died (33. 3% ). In group Ⅲ , biochemical indexes changed obviously 12 h after the administration and hepatic injury reached its peak after 48 h. Ten of 12 rabbits were died of severe hepatic failure with a survival time of ( 53. 00 ± 25. 69) h. Histology of liver section revealed massive necrosis in nodules. In group Ⅳ , hepatic injury occurred early and severely. All the rabbits died of severe hepatic failure with a survival time of (32. 70 ± 17. 46) h. Conclusion The experimental model of ACLF could be established by injected with D-Gal in New Zealand rabbits with hepatic fibrosis, induced by CCl4 intraperitoneal injection for 10 weeks.The one induced by 0. 70 g/kg of D-galactosamine was more stable and showed similar clinical pathophysiological changes in human beings. So it can be a good experimental platform for studies of ACLF.     

结肠切除吻合术大鼠动物模型的建立

目的构建结肠切除吻合术大鼠动物模型。方法2019年9月至2019年12月将12只Sprague-Dawley大鼠通过随机数表随机分为两组:对照组随机取3只,仅做剖腹探查;实验组9只,从结肠无血管区离断肠管并进行缝合。记录手术时间,术后监测体重变化。于术后第7天进行肠道造影观察肠管吻合口愈合情况。于第8天行剖腹探查大鼠腹腔内部形态学变化,测量吻合口爆破压力,并通过采集吻合口及周围组织,进一步观察吻合口组织学的变化,计量资料采用t检验。结果该模型构建平均时间为22 min。大鼠的存活率为89%。造影显示肠管通畅,无梗阻。剖腹探查,肉眼可见吻合口存在轻微粘连,粘连部分可分离,吻合口周围有血管组织形成。与对照组比较,实验组苏木精-伊红染色可见吻合口有新生肉芽组织形成,并有小血管生成,未发现结肠上皮、大肠腺的存在。马松染色可见胶原纤维沉积。结论通过该方法可成功构建结肠切除吻合术大鼠动物模型。     

肝动脉重建的小鼠原位肝移植模型建立

目的 建立稳定的肝动脉重建的小鼠原位肝移植模型.方法 以"双袖套法"小鼠肝移植为基础,将带腹主动脉的供肝肝动脉与受体腹主动脉行端侧吻合.共完成小鼠原位肝移植70例,并观察术后24 h、1周、1个月受体存活率,术后1个月肝功能及肝组织病理变化.同时设立假手术组对照.结果 受体术后24 h、1周、1个月存活率分别为94.3%、91.4%、85.7%.术后1个月肝功能ALT:(39.20±2.09)U/L AST:(75.60±3.24)U/L.与对照组比较,差异无统计学意义(P>0.05).病理显示肝组织结构良好.结论 该方法可稳定地建立肝动脉重建的小鼠原位肝移植模型.     

肝动脉重建的小鼠原位肝移植模型建立

目的 建立稳定的肝动脉重建的小鼠原位肝移植模型.方法 以"双袖套法"小鼠肝移植为基础,将带腹主动脉的供肝肝动脉与受体腹主动脉行端侧吻合.共完成小鼠原位肝移植70例,并观察术后24 h、1周、1个月受体存活率,术后1个月肝功能及肝组织病理变化.同时设立假手术组对照.结果 受体术后24 h、1周、1个月存活率分别为94.3%、91.4%、85.7%.术后1个月肝功能ALT:(39.20±2.09)U/L AST:(75.60±3.24)U/L.与对照组比较,差异无统计学意义(P>0.05).病理显示肝组织结构良好.结论 该方法可稳定地建立肝动脉重建的小鼠原位肝移植模型.