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国际生物医学工程杂志
国际生物医学工程杂志

李迎新

双月刊

1673-4181

guobjb@yahoo.com.cn

022-87895652

300192

天津市南开区白堤路236号中国医学科学院生物医学工程研究所编辑部

国际生物医学工程杂志/Journal International Journal of Biomedical Engineering北大核心CSTPCD
查看更多>>中华医学会、中国医学科学院生物医学工程所主办。本刊专门报导国内外生物医学工程学科领域的新技术、新进展、新动向与新成果，促进国际生物医学工程学科的学术交流。本刊不仅全面、及时地介绍和跟踪了国际生物医学工程的研究进展与趋势，也反映了我国生物医学工程学科的研究动向和关注热点。读者对象是生物医学工程科研工作者、医生和临床工程人员、高等院校有关专业师生及研究生等。主要栏目设有专家论坛、综述、论著、研究简报、新技术介绍及消息等。本刊为中文核心期刊（北京大学图书馆）及中国科技论文统计源期刊（中国科技核心期刊）。
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    一氧化氮医疗器械的创新发展之路

    赵强钱盟卫永禛
    1-5页
    查看更多>>摘要：1992年，著名学术期刊Science发表了一氧化氮的文章，题为"NO news is good news"，并登上了当期的封面，而一氧化氮也成为年度"明星分子"[1]。1998年，美国3位科学家罗伯·佛契哥特、路伊·格纳洛和费瑞·慕拉德因"一氧化氮在心血管系统中的转导机制"研究而获得诺贝尔生理学或医学奖。同时，也揭开了困扰科学家百年的硝酸甘油作用机制之谜[2]。硝酸甘油正是诺贝尔发明的炸药的主要成分。瑞典发明家阿尔弗雷德·诺贝尔利用硝酸甘油为原料，经过不懈努力，成功地发明了安全炸药。诺贝尔也因此获得了巨大的财富。与此同时，药理学家们也将硝酸甘油发展成一种缓解心绞痛的药物。1879年，威廉·默雷尔在Lancet上发表了硝酸甘油缓解心绞痛的文章。而诺贝尔晚年也患有心脏病，医生给他开的药物就是硝酸甘油，但他始终拒绝服用因此影响了心脏病的治疗。1896年，诺贝尔去世，他在遗嘱中说明设立诺贝尔奖金，以奖励那些在医学、物理、化学和文学等方面做出最杰出贡献的科学家。有人说，如果诺贝尔在世，会亲自为这3位科学家发奖。他们的获奖成果和诺贝尔有着千丝万缕的联系。
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    无创神经调控新技术与发展趋势

    殷涛
    6-9页
    查看更多>>摘要：阿尔茨海默症、帕金森病和抑郁症等神经系统疾病给全球公共卫生和经济领域带来了巨大的负担，脑功能性疾病已成为全球最主要的致残和致死原因之一[1]。目前对人类大脑的探索和认知还处在初级阶段，对脑疾病仍然缺乏行之有效的预防与治疗手段。自2013年始，西方发达国家或组织陆续提出了和人类脑科学研究相关的计划或战略规划，我国也把脑科学研究列为了"事关我国未来发展的重大科技方向"，2021年我国正式发布并启动中国脑科学研究计划[2]。
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    电磁弹射式内镜缝合器的设计和实验研究

    殷东明李雨嘉胡钟欣耿钊宁...
    10-16页
    查看更多>>摘要：目的 设计一种新型的用于内镜缝合的电磁弹射器，以实现缝合钉的连续发射。 方法 依据电磁弹射的基本原理，设计缝合钉结构和电磁弹射装置，并制作样机；构建电磁弹射装置的有限元模型，研究电枢-线圈中心距和不同驱动电压对缝合钉出射速度的影响；搭建电磁弹射速度实验平台，采用高速摄影机对出射速度进行检测；搭建缝合钉嵌入实验平台，测量不同电压下发射速度对嵌入胃壁组织的影响；搭建缝合钉拔出力实验平台，对不同驱动电压下缝合钉嵌入组织的效果进行拔出力评估。 结果 设计了缝合钉结构和电磁弹射装置，并制作了样机。出射速度随着电枢-线圈中心距的增大，先增加后降低，且在中心距为18 mm时，出射速度最大，为15.81 m/s。中心距为18 mm时，电压与出射速度呈线性关系，缝合钉实验值与仿真值基本吻合。驱动电压为150～180 V时，缝合钉均可成功嵌入组织中，且180 V电压组的嵌入程度更深。120、150、180和210 V电压下缝合钉的拔出力分别为（0.49±0.19）、（1.14±0.19）、（1.23±0.15）、（1.85±0.31）N。 结论 设计了一种新型的电磁弹射式内镜缝合器，能够实现缝合钉连续发射，为智能化微创外科手术器械提供了一种新的远距离驱动方式。 Objective To design a novel electromagnetic ejection device for endoscopic suturing to achieve continuous deployment of suture nails. Methods An electromagnetic ejection device and its accompanying suture nail structure were designed and a prototype was fabricated based on electromagnetic ejection principles. A finite element model of the electromagnetic ejection device was constructed to study the effects of armature-coil center distance and different driving voltages on suture nail ejection speed. An experimental platform for testing electromagnetic ejection velocity was constructed, and a high-speed camera was used to detect the ejection velocity. A platform for the suture embedding experiment was built to measure the effects of different voltages on the inserting speed of suture into the gastric wall tissue. A platform for a suture extraction force experiment was built to evaluate the extraction force of sutures embedded in tissues under different driving voltages. Results A suture nail structure and electromagnetic ejection device were designed, and a prototype was fabricated. The ejection velocity increased and then decreased with the increase of the armature-coil center distance, and the maximum ejection velocity was 15.81 m/s at the center distance of 18 mm. At this distance, the voltage was linearly related to the ejection velocity, and the experimental values of the staple basically coincided with the simulated values. When the driving voltage was in the range of 150 to 180 V, the suture nails could successfully insert in the tissues, and the 180 V voltage group had a greater insertion depth. The extraction force of the suture nails at 120, 150, 180, and 210 V voltages were (0.49 ± 0.19), (1.14 ± 0.19), (1.23 ± 0.15), and (1.85 ± 0.31) N, respectively. Conclusions A novel electromagnetic ejection device for endoscopic suturing is proposed that is capable of continuous firing of suture nails. This device provides a new long-distance driving method for intelligent, minimally invasive surgical instruments.

    内镜缝合器电磁弹射微创手术建模与仿真离体实验

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    基于金属编织技术的柔性机械手结构设计与实验验证

    童子龙徐波孙丽萍陆鑫涛...
    17-23页
    查看更多>>摘要：目的 开发一种应用于经自然腔道内镜手术（NOTES）机器人柔性机械手的骨架结构，以满足NOTES对手术执行器械的性能需求。 方法 基于金属编织技术设计一种柔性机械手结构及对应结构的控制策略。根据柔性机械手的机械结构特征推导几何关系公式。通过链式梁约束模型（CBCM）以及机械弹簧理论建立理论模型。对机械结构建立有限元模型并分析，验证理论模型的精度；并由金属编织结构的抗弯刚度验证柔性机械手的载荷能力。 结果 基于金属编织技术设计了一种柔性机械手结构及对应结构的控制策略。在设置恰当的约束条件后，金属圆环作为单个受力单元在受到0.5 N的轴向力驱动时，最大应变约为1.49%，处于线性弹性阶段。最大形变约为0.308 9 mm，比理论值高3.26%。机械手骨架的最大应变约为0.21%，处于线性弹性阶段。最大总形变约为7.135 5 mm，比理论值高6.30%。机械手骨架的抗弯刚度计算为3.19 N·mm2，与同量级尺寸形状记忆聚合物（SMPs）制成的柔性机械手相当。 结论 开发一种应用于NOTES机器人柔性机械手的骨架结构，符合执行NOTES手术任务的支撑刚度需求。 Objective To develop a skeleton structure for the flexible manipulator of a robotic system used in natural orifice transluminal endoscopic surgery (NOTES), meeting the performance requirements of surgical actuators. Methods A flexible manipulator structure and a control strategy for the corresponding structure were designed based on metal braiding technology. Geometric relationship formulas were derived according to the mechanical structure characteristics of the flexible manipulator. A theoretical model was established using the chained beam-constraint-model (CBCM) and mechanical spring theory. The finite element model of the mechanical structure was established, and simulation analysis was performed to verify the accuracy of the theoretical model. The bending stiffness of the metal-braided structure was tested to verify the load capacity of the flexible manipulator. Results A flexible manipulator structure and a control strategy for the corresponding structure were designed based on metal braiding technology. With proper constraints, the maximum strain of the metal ring as a single stressed unit was about 1.49% when subjected to an axial force of 0.5 N. At this time, the material was in the linear elastic phase and the maximum deformation was about 0.308 9 mm, which was 3.26% higher than the theoretical value. The maximum strain of the manipulator skeleton was about 0.21% in the linear elastic phase. The maximum total deformation was about 7.135 5 mm, which was 6.30% higher than the theoretical value. The flexural stiffness of the manipulator skeleton was calculated to be 3.19 N·mm2, which was comparable to a flexible manipulator made of shape memory polymers (SMPs) of the same magnitude and size. Conclusions A skeleton structure for application to NOTES robotic flexible manipulators is developed that meets the support stiffness requirements for performing NOTES surgical tasks.

    机器人经自然腔道内镜手术编织结构柔性机械手

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    兔尿道瘢痕超声治疗仪的设计与实现

    王欣钰刘畅卜朝晖郑其斌...
    24-32页
    查看更多>>摘要：目的 设计一台专用于兔尿道瘢痕的超声治疗仪，旨在验证此仪器的适用性及有效性。 方法 以新西兰雄兔为实验对象，针对其阴茎结构与尺寸对超声治疗仪进行特制，此超声治疗仪包括超声脉冲发射与控制系统、末级功放和超声探头。首先，针对兔阴茎尺寸及结构对超声探头进行设计，并通过COMSOL有限元仿真以及声场分布实际测试等确定超声探头的参数；其次，根据超声探头元件参数设计其驱动电路；然后，设计基于现场可编程门阵列（FPGA）和串口屏的超声脉冲发射与控制系统；接着，对整体完成的超声治疗仪进行整体性能测试和安全测试；最后，构建兔尿道重建模型，将8只白兔随机分为模型组和实验组，实验组立即接受该超声治疗仪对其尿道部位的治疗，参数设置为超声频率2 MHz，脉冲间隔10 ms，输出声强0.73 W/cm2。治疗频率为2次/周（周二、四），每次照射10 min，持续4周；模型组则不接受任何治疗，用Image J软件对兔尿道组织中转化生长因子-β1（TGF-β1）、基质金属蛋白酶-2（MMP-2）和肿瘤坏死因子-α（TNF-α）染色阳性区域的面积占比进行定量分析，并计算尿道周长。 结果 添加了吸声材料的结构治疗腔内声压分布较为均匀，驻波比均值为1.11，结构设计满足设计期望。整体性能测试中3枚超声换能器自然焦点位置均为10 mm，声场分布一致性满足实验要求。各换能器峰值声压与电源电压关系接近线性。输出声强范围为0.35～0.74 W/cm2，满足实验要求。随着超声输出，测试点温度缓慢升高，此实验最高可使组织温度升高3.3 ℃，不会导致组织热损伤发生。动物实验表明，实验组兔尿道组织中TGF-β1免疫阳性面积分数[（4.21±1.32）%]小于模型组[（8.53±3.43）%]（t＝−4.24，P<0.001）；实验组兔尿道组织中TNF-α免疫阳性面积分数[（5.14±2.72）%]小于模型组[（7.23±1.57）%]（t＝−3.37，P<0.05）；实验组兔尿道组织中MMP-2水平[（10.65±2.24）%]高于模型组[（6.98±2.74）%]（t＝2.19，P<0.05）；尿道周长[（12 209±2 743）μm]高于模型组[（10 127±2 237）μm]（t＝15.46，P<0.05）。 结论 成功设计了一台专用于兔尿道瘢痕的超声治疗仪，可用于超声对兔尿道瘢痕治疗的研究。 Objective To design a specialized ultrasound therapeutic device for rabbit urethral scars and to verify its applicability and effectiveness. Methods New Zealand male rabbits were used as the experimental objects, and the ultrasound therapeutic instrument was customized according to the structure and size of the rabbit penises. The ultrasound therapeutic instrument included the ultrasound pulse emission and control system, the final-stage amplifier, and the ultrasound probe. Firstly, the ultrasound probe was designed according to the size and structure of rabbit penises, and the parameters of the ultrasound probe were determined by COMSOL finite element simulation and actual testing of the sound field distribution. Secondly, the driving circuit of the ultrasound probe was designed according to the parameters of the elements. Then the ultrasound pulse emission and control system based on the field-programmable gate array (FPGA) and the serial screen were designed. Subsequently, the ultrasound therapeutic instrument was subjected to a performance test and a safety test. The ultrasound therapeutic instrument was constructed to include the ultrasound amplifier and the ultrasound probe. Finally, a rabbit urethra reconstruction model was constructed, and eight white rabbits were randomly divided into a model group and an experimental group. The rabbits in the experimental group received the ultrasound therapeutic instrument for treatment of the urethra immediately, with an ultrasound frequency of 2 MHz, a pulse interval of 10 ms, and an output sound intensity of 0.73 W/cm2. The treatment was performed twice a week (on Tuesday and Thursday), with 10 min of irradiation each time, lasting for four weeks. The rabbits in the model group did not receive any treatment. The area percentage of transforming growth factor-β1 (TGF-β1), matrix metalloproteinase-2 (MMP-2), and tumor necrosis factor-α (TNF-α) staining-positive areas in rabbit urethral tissues were quantitatively analyzed, and the urethral circumference was calculated using Image J software. Results Due to the addition of sound-absorbing materials, the sound pressure distribution in the treatment chamber was more uniform, and the average value of the standing wave ratio was 1.11, indicating that the structural design met the design requirements. In the overall performance test, the natural focal position of the three ultrasonic transducers was 10 mm, and the consistency of the sound field distribution meet the experimental requirements. The relationship between the peak sound pressure of each transducer and the power supply voltage was close to linear. The output sound intensity ranged from 0.35 to 0.74 W/cm2, which met the experimental requirements. With the ultrasound output, the temperature of the test point increased slowly, and this experiment could increase the temperature of the tissue by up to 3.3 ℃, which would not lead to thermal damage to the tissue. Animal experiment results showed that the immunopositive area fraction of TGF-β1 in the urethral tissues of rabbits in the experimental group [(4.21 ± 1.32)%] was smaller than that of the model group [(8.53 ± 3.43)%] (t = −4.24, P < 0.001). The immunopositive area fraction of TNF-α in the urethral tissues of rabbits in the experimental group [(5.14 ± 2.72)%] was smaller than that of the model group [(7.23 ± 1.57)%] ( t = −3.37, P < 0.05). The MMP-2 level in the urethral tissue of rabbits in the experimental group [(10.65 ± 2.24)%] was higher than that of the model group[(6.98 ± 2.74)%] ( t = 2.19, P < 0.05). The urethral circumference [(12 209 ± 2 743) μm] was higher than that of the model group [(10 127 ± 2 237) μm] ( t = 15.46, P < 0.05). Conclusions An ultrasound therapeutic instrument dedicated to rabbit urethral scars has been successfully designed and can be used for the study of ultrasound treatment of rabbit urethral scars.

    超声尿道瘢痕转化生长因子-β1基质金属蛋白酶-2肿瘤坏死因子-α

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    红细胞和血小板作为载体用于抗肿瘤药物递送的研究进展

    史照青卢诗曼梅林
    33-38页
    查看更多>>摘要：红细胞和血小板在血液中广泛存在，易于从血液中分离，且性质相对稳定，是一种理想的药物递送载体。近年来，大量研究利用红细胞和血小板递送抗肿瘤药物以实现高效的药物递送，其在优化药物体内行为、增加疗效以及减少给药剂量方面表现出了优异的效果。此外，其细胞膜可用作包膜材料以改善纳米药物递送系统的性质，实现仿生功能的同时减少纳米粒的毒副作用。介绍了红细胞和血小板及其膜材料的特性和制备方法，以及其在抗肿瘤药物递送中的研究进展。 Red blood cells and platelets are widely present in the blood. They are easily isolated from the blood and relatively stable in nature, making them an ideal drug delivery vehicle. In recent years, a large number of studies have been conducted to use red blood cells and platelets to deliver antitumor drugs and achieve efficient drug delivery. Red blood cells and platelets have shown excellent results in optimizing the in vivo behavior of drugs, increasing efficacy, and reducing the dose administered. In addition, its cell membrane can be used as a coating material to improve the properties of nanodrug delivery systems and achieve biomimetic functions while reducing the toxic side effects of nanoparticles. The characteristics and preparation methods of red blood cells and platelets and their membrane materials were introduced, and their diagnostic and therapeutic applications in antitumor drug delivery was looked forward.

    红细胞血小板药物递送系统肿瘤治疗

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    基于细胞外囊泡的递送系统研究进展

    金丽敏吕丰董霞
    39-44页
    查看更多>>摘要：细胞外囊泡是一种来源于内体和细胞膜的多样化的膜性囊泡，在细胞间通讯中发挥关键作用。严格的生物发生途径赋予细胞外囊泡广泛的来源和特殊的亲本特性，复杂的内容物及表面蛋白有利于受体细胞的识别。细胞外囊泡依靠天然的生物相容性和囊泡结构来容纳更多的功能生物分子，是一种极具潜力的药物递送载体。主要介绍了细胞外囊泡的分类及生物学功能、在不同类型药物递送中的特点，讨论了细胞外囊泡在疾病治疗中的应用以及细胞外囊泡递送系统的临床转化和挑战。 Extracellular vesicles are recognized as a kind of membranous vesicle derived from endosomes and cell membranes that play important roles in intercellular communication. Strict biogenesis pathways dictate that extracellular vesicles have a wide range of origins and specific parental characteristics, while complex contents and surface proteins facilitate their recognition by receptor cells. Extracellular vesicles are considered a promising drug delivery system due to their natural biocompatibility and vesicle structure, where more functional biomolecules can be accommodated. The classification, biological functions, and characteristics of extracellular vesicles in different types of drug delivery were introduced. The application of extracellular vesicles in disease therapy and the clinical transformation and challenges of the extracellular vesicle delivery system were discussed.

    细胞外囊泡细胞间通讯靶向递送

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    工程微生物在不同疾病治疗中的应用进展

    陈婷李稳
    45-52页
    查看更多>>摘要：人体包含了一个由真核生物、古细菌、细菌和噬菌体等组成的庞大微生物群落。细菌是其中最主要的成员，其数量与人体细胞的数量级相同。许多共生或致病的细菌都会通过生化信号与宿主相互作用。基于这些细菌特性，共生和减毒病原菌已被设计用于递送治疗分子以靶向性治疗特定疾病。介绍了近5年发展的工程微生物或微生物衍生颗粒及其封装、分泌、表达表面治疗分子，综述了其在炎症性肠病及胃病、肿瘤和心血管疾病治疗中的应用进展，并探讨了微生物药物递送系统的临床转化潜力。 The human body contains a large microbial community composed of eukaryotes, archaea, bacteria, and phages. Bacteria are the most prominent members of this community, numbering in the same order of magnitude as human cells. Many commensal or pathogenic bacteria interact with their hosts through biochemical signals. Based on these bacterial properties, commensal and attenuated pathogens have been designed to deliver therapeutic molecules to target specific diseases. The engineered bacteria or bacteria-derived particles and their encapsulation, secretion, and expression of surface therapeutic molecules developed in the past five years were introduced. Their applications in anti-inflammatory, anti-tumor, thrombosis treatment, and imaging were reviewed, and the clinical translational potential of microbial drug delivery systems was discussed.

    微生物表面修饰基因工程抗炎抗肿瘤

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    融合C3Fab抗PD-L1纳米抗体的制备及其对血浆半衰期的影响

    王展雄雷萌邓奕辰娄楚...
    53-59页
    查看更多>>摘要：目的 制备融合C3Fab的抗程序性死亡-配体1（PD-L1）纳米抗体P3C8-C3Fab，并研究其对血浆半衰期的影响。 方法 将来源于蛋白G的C3Fab肽段，通过DNA重组技术与纳米抗体P3C8进行分子融合，并构建重组质粒pET21a-P3C8-C3Fab，在大肠杆菌BL21菌株中进行诱导表达和纯化，并采用酶联免疫吸附试验（ELISA）检测P3C8-C3Fab与PD-L1蛋白、小鼠IgG和表达PD-L1肿瘤细胞的结合，利用双抗夹心ELISA检测不同时间小鼠血清中残留P3C8-C3Fab，以评估C3Fab对PD-L1纳米抗体血浆半衰期的延长作用。 结果 成功构建了融合C3Fab的抗PD-L1纳米抗体P3C8-C3Fab，其在BL21菌中以可溶形式高效表达，经纯化获得质量分数约为90%的NbP3C8-C3Fab蛋白，得率为7.18 mg/L。P3C8-C3Fab随着质量浓度的增加，对PD-L1蛋白和小鼠IgG亲和力也逐渐升高，且呈现浓度相关性；P3C8-C3Fab与肺癌A549细胞的结合呈浓度相关性。小鼠血清中P3C8-C3Fab的浓度标准曲线呈典型的S型浓度相关性；P3C8血浆半衰期仅为0.44 h，而P3C8-C3Fab的血浆半衰期达到9.36 h，血浆半衰期延长了21.27倍。 结论 C3Fab与纳米抗体P3C8连接可以显著延长其血浆半衰期，对改善纳米抗体的体内作用具有应用价值。 Objective To prepare the anti-programmed death-ligand 1 (PD-L1) nanoantibody P3C8-C3Fab by ligating with C3Fab and to investigate its role in plasma half-life. Methods The C3Fab peptide derived from protein G was molecularly fused with the nanobody P3C8 by DNA recombination technology. The nanoantibody P3C8-C3Fab was inducibly expressed and purified in the E. coli BL21 strain, and the binding of it to PD-L1 protein, mouse IgG, and PD-L1-expressing tumor cells was detected by enzyme-linked immunosorbent assay (ELISA). The residual P3C8-C3Fab was detected in mouse serum at different times using double-antibody sandwich ELISA to assess the prolongation of the plasma half-life of PD-L1 nanobodies by C3Fab. Results The nanoantibody P3C8-C3Fab was successfully constructed, and it could efficiently express itself in soluble form in BL21. The purified NbP3C8-C3Fab protein was obtained with a mass fraction of about 90% at a yield of 7.18 mg/L. The affinity of P3C8-C3Fab for PD-L1 protein and mouse IgG gradually increased with increasing mass concentration and showed a concentration correlation. The binding of P3C8-C3Fab to lung cancer A549 cells showed a concentration correlation. The concentration standard curve of P3C8-C3Fab in mouse serum showed a typical S-shape with a concentration correlation. The plasma half-life of P3C8 was only 0.44 h, while the plasma half-life of P3C8-C3Fab was 21.27-fold higher, up to 9.36 h. Conclusions The linkage of C3Fab to the nanobodies of P3C8 can significantly prolong the plasma half-life of P3C8, which is valuable for the improvement of in vivo nanobody effects.

    程序性死亡受体-1纳米抗体半衰期IgG结合肽C3Fab

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    小鼠青春期前和青春期早期海马颗粒细胞γ-氨基丁酸受体电流的研究

    刘爱丽田超谌辉
    60-65页
    查看更多>>摘要：目的 探讨青春期前期和青春期早期雌性小鼠海马齿状回颗粒细胞γ-氨基丁酸（GABA）受体电流的变化。 方法 以雌性小鼠为研究对象，3～4周龄小鼠为青春期前期组（n＝6），5～6周龄小鼠为青春期早期组（n＝6）。采用全细胞膜片钳技术，记录青春期前后海马颗粒细胞GABA受体自发抑制性突触后电流（sIPSC）、微小抑制性突触后电流（mIPSC）和tonic电流，并分析其变化。 结果 青春期前期组和青春期早期组小鼠sIPSC的发放频率分别为（2.22±0.12）、（2.30±0.21）Hz，幅值分别为（19.97±2.01）、（23.80±2.86）pA，两组小鼠sIPSC发放频率和幅值比较差异均没有统计学意义（均P>0.05）；青春期前期组和青春期早期组小鼠sIPSC发放频率和幅值的累积概率比较差异均无统计学意义（均P>0.05）。青春期前期组和青春期早期组小鼠mIPSC的发放频率分别为（0.87±0.08）、（2.15±0.21）Hz，幅值分别为（12.51±0.11）、（29.67±0.19）pA，较青春期前期相比，青春期早期小鼠海马颗粒细胞GABA受体mIPSC发放频率升高（P<0.001），幅值增大（P<0.001）。青春期前期组和青春期早期组小鼠sIPSC发放频率和幅值的累积概率比较差异均有统计学意义（均P<0.001）。青春期前期组和青春期早期组小鼠GABA受体tonic电流分别为（17.40±1.64）、（24.70±2.81）pA，两组小鼠GABA受体tonic电流比较差异具有统计学意义（P<0.05）。 结论 青春期早期雌性小鼠颗粒细胞GABA受体电流较青春期前期有所增强，雌性小鼠进入青春期早期时海马颗粒细胞抑制性活动增强。 Objective To investigate the changes in γ-aminobutyric acid (GABA) receptor currents of hippocampal dentate gyrus granule cells in prepubertal and early pubertal female mice. Methods Female mice were selected as the study objects 3 to 4 -week-old mice were selected as the pre-puberty group (n=6) and 5 to 6 -week-old mice were selected as the puberty group (n=6). The whole-cell patch clamp technique was used to record the spontaneous inhibitory post-synaptic current (sIPSC), mini-inhibitory post-synaptic current (mIPSC), and tonic current of hippocampal granulosa cells in the DG region of pre-pubertal and early pubertal female mice, and their changes were analyzed. Results The frequency of sIPSC in the pre-puberty group and puberty group was (2.22 ± 0.12) Hz and (2.30 ± 0.21) Hz, respectively. The amplitude of sIPSC in the pre-puberty group and the puberty group was (19.97 ± 2.01) pA and (23.80 ± 2.86) pA, respectively. The experimental results showed no significant changes in frequency and amplitude of sIPSC of hippocampal granulosa cells in pre-pubertal and early pubertal mice (all P > 0.05), and no statistical significance in the cumulative frequency and amplitude of sIPSC between two groups (all P > 0.05). The frequency of mIPSC in the pre-puberty group and the puberty group was (0.87 ± 0.08) Hz and (2.15 ± 0.21) Hz, respectively. The amplitude of mIPSC in the pre-puberty group and puberty group was (12.51 ± 0.11) pA and (29.67 ± 0.19) pA, respectively. Compared with the pre-pubertal mice, the frequency and amplitude of mIPSC from hippocampal granulosa cells in early pubertal mice are significantly increased ( P < 0.001). There was also a significant difference in the cumulative frequency and amplitude of sIPSC between the two groups ( P < 0.001). The tonic current of the pre-puberty group and puberty group was (17.40 ± 1.64) pA and (24.70 ± 2.81) pA, respectively, and the tonic current in early pubertal mice was significantly higher than that in pre-pubertal mice ( P < 0.05). Conclusions GABA receptor current is enhanced in early pubertal female mice compared with pre-pubertal females. The inhibitory activity of hippocampal granulosa cells in early adolescent female mice was increased.

    青春期γ-氨基丁酸受体抑制性突触电流

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