新生雄性小鼠肾脏连续切片的三维重建实验研究
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摘要
目的:近半个世纪以来有关致畸因素以及致畸机理的研究进展很快,各种先天性泌尿生殖系统畸形动物模型已被成功制作。但既往研究对于畸形存在与否及严重程度的评估主要是靠较粗略的人工观察和测量,如观察睾丸下降的位置、生殖器官重量变化、肛门生殖器间的距离、包皮分离程度等。上述指标都是基于观察者人工进行,由于观察者的不同其结果差异很大,导致目前畸形判定难以量化,畸形形态学量化研究也一直进展不大。计算机三维重建技术可以对生物组织的连续平面图像进行综合、计算并重建显示其立体的三维结构,同时还可对重建的三维结构进行测量,获得长度、面积、体积等大量精确的形态学参数,最重要的是可以避免人为的误差。为此,本研究通过对外源性雌激素(己烯雌酚DES)作用下的新生小鼠肾脏采用整体原位固定、连续组织切片进行三维重建,测算外源性雌激素作用前后小鼠肾脏的体积、表面积、长轴、短轴的变化,探讨进一步量化研究小鼠泌尿生殖系统形态结构及畸形的可行方法。
材料与方法:8~10周龄雌性昆明小鼠30只随机平均分成3组:正常组、对照组及实验组。常规交配受孕后,正常组不给任何药物;于孕9～17天时,对照组皮下注射二甲基亚砜(DMSO)和生理盐水;实验组皮下注射己烯雌酚(DES)100ug/kg/d,DES溶于DMSO和生理盐水中。待母鼠生产后尽快取出全部仔鼠集中,行解剖性别确认(观察肛门生殖器间距离)。每组雄性仔鼠各随机抽取五只,自隔下切取下腹部固定、包埋。以5μm厚分别作横断面连续切片,常规HE染色。在带数字照相记录的生物显微镜下按一定顺序摄取图像,以JPG格式存入移动硬盘中。在40倍和100倍显微镜下观察肾小球及肾小管发育情况,使用物镜和目镜测微尺系统测定切片中肾脏横断面的长短轴实际长度通过Photoshop8.0.1、CATIA V6软件对小鼠肾脏进行三维重建获取其体积、表面积和轴比等形态学参数。
结果:1.正常组、对照组新生小鼠整体躯干体积明显大于实验组新生小鼠,但解剖观察无法区别它们肾脏的体积变化。2.正常组及对照组新生小鼠肾脏横断面连续切片显微观察显示小鼠肾脏表面平滑,肾盂内只有一个乳头(单乳头),肾小球和相关的管道系统发育良好。实验组与正常组相同无异常。3.三维重建后可获得新生小鼠双侧肾脏的立体图像及总体积、总表面积、轴比等形态学参数。①正常组小鼠肾脏总体积左右分别为11778477.518±181412和11261295.434±163506μm3,总表面积左右分别为386038.301±1670和386610.607±941μm2,轴比左肾为0.85,右肾为0.86;②对照组小鼠肾脏总体积左右分别为11779367.918±106141和11261191.984±134263μm3,总表面积左右分别为386012.104±678和386409.907±584μm2,轴比左右均为0.85;③实验组小鼠肾脏总体积左右分别为9770964.044±107921和10211541.613±106863μm3,总表面积左右分别为318097.638±1270和327367.436±310μm2,轴比左右均为0.85,均明显小于正常及对照组。正常及对照组小鼠肾脏体积、表面积比较无统计学差异(P>0.05),但与实验组比较均有统计学差异(P< 0.05)。
结论:1.应用组织器官系统整体原位固定、连续组织切片对新生小鼠肾脏进行三维重建可行性好,它不仅能重建该器官的整体形态结构,而且可获得较精确的形态学参数。2.应用组织器官系统整体原位固定、连续组织切片三维重建的方法可辩别器官细微的整体形态变化,这对于传统的肉眼观察具有不可比拟的优势。3.孕期暴露DES可引起雄性新生小鼠肾脏体积缩小。4.应用组织器官系统整体原位固定、连续组织切片对新生小鼠肾脏进行三维重建的方法将为更为复杂、精细的泌尿生殖系统形态学量化研究奠定基础。
Objective:In the half century,the mechanisms of congenital abnormalities studies were advanced quickly,the animal models of congenital abnormalities have been made successly.However, in the old study,whether there were abnormalities and how about the degrees mainly depended on manual watch and measure ,such as,the location of testis,the weight of genital organs,the distance of anus and genitals,the separation of prepuce,etc. Because these results were acquired by different observer,they were not consistent frequently,and it is difficult to confirm the malformation accurately,the study of malformation morphology advance slowly.The computer three-dimensonal reconstruction can reconstruct the organs by serial slices,and calculate the length、volume、area of organs,it is the most important to avoid the manual error.In this study,the kidneise of newborn mice were reconstructed by serial slices,and calculate their volume and area,hope to find elaborate method to evaluate urogenital system malformations.
Materials and methods:30 8-10 weeks old Kunming female mice were divided into three groups randomly,that is :normal group(not given any drug),contral group (given DMSO and NS),and experimental group(DES was given 100ug/kg/d).Pregnant mice were injected subcutaneously from GD9(gestation day)to GD17.The newborn mice,when they were delivered, were collected at once for the determination of sexuality.And then,five male mice of them were randomly selected from each group.All the selected newborn mice were treated as follows:the low parts of abdomen were fixed in situ and set to transected serial slice.All the slices(HE prepared and 5μm thick) were studied under microscopy and recorded serially in JPG form.The 3D-reconstruction were being made by the soft of Photoshop 8.0.1 and CATIAV6.
Result:1.The volume of newborn mice in normal and control groups are bigger than the experimental group obviously,but the size of kidneies are very difficult to distinguish by dissection observation in all groups.2. In the serial transects of normal newborn mice, the kidney were all in round shape and the curves were smooth,and they have only one renal papilla,the glumerular and tubular were well developed.There were no difference in the other two groups.3.After 3D-reconstruction,the 3D picture of kidney and some morphologicalparameters were acquired:①In the normal group,the volume of left and right kidney was about 11778477.518±181412and 11261295.434±163506μm3respectively;the area of left and right kidney was about 386038.301±1670and 386610.607±941μm2respectively,the ratio of long-short axis of left kidney was 0.85,and the right kidney was 0.86.②In the control group, the volum e of left and right kidney was about 11779367.918±106141and 11261191.984±134263μm3 respectively;the area of left and right kidney was about 386012.104±648 and 386409.907±584μm2respectively , the ratios of long-short axis were all 0.85.③In the experimental group, the volume of left and right kidney was about9770964.044±107921and 10211541.613±106863μm3respectively; the area of left and right kidney was about 318097.638±1270 and 327367.436±310μm2 respectively,the ratios of long-short axis were all 0.85.The volume and area of kidney were all smaller obviously than that of normal and control groups(P< 0.05).
Conclusion:1.Method of reconstructing the 3D picture of newborn mice kidney with serial tissue sections is feasible. It not only can reconstruct the 3D picture of newborn mice kidney,but also acquire precise morphology parameter.2.Method of reconstructing the 3D picture with serial tissue sections can distinguish the fine difference of the tiny organ morphology,it is better than manual observation.3.Exposure to DES make the newborn mice kidney smaller.4.The method of reconstructing the 3D picture of newborn mice kidney with serial tissue sections is the foundation of urogenital system 3D-reconstruction.
材料与方法:8~10周龄雌性昆明小鼠30只随机平均分成3组:正常组、对照组及实验组。常规交配受孕后,正常组不给任何药物;于孕9～17天时,对照组皮下注射二甲基亚砜(DMSO)和生理盐水;实验组皮下注射己烯雌酚(DES)100ug/kg/d,DES溶于DMSO和生理盐水中。待母鼠生产后尽快取出全部仔鼠集中,行解剖性别确认(观察肛门生殖器间距离)。每组雄性仔鼠各随机抽取五只,自隔下切取下腹部固定、包埋。以5μm厚分别作横断面连续切片,常规HE染色。在带数字照相记录的生物显微镜下按一定顺序摄取图像,以JPG格式存入移动硬盘中。在40倍和100倍显微镜下观察肾小球及肾小管发育情况,使用物镜和目镜测微尺系统测定切片中肾脏横断面的长短轴实际长度通过Photoshop8.0.1、CATIA V6软件对小鼠肾脏进行三维重建获取其体积、表面积和轴比等形态学参数。
结果:1.正常组、对照组新生小鼠整体躯干体积明显大于实验组新生小鼠,但解剖观察无法区别它们肾脏的体积变化。2.正常组及对照组新生小鼠肾脏横断面连续切片显微观察显示小鼠肾脏表面平滑,肾盂内只有一个乳头(单乳头),肾小球和相关的管道系统发育良好。实验组与正常组相同无异常。3.三维重建后可获得新生小鼠双侧肾脏的立体图像及总体积、总表面积、轴比等形态学参数。①正常组小鼠肾脏总体积左右分别为11778477.518±181412和11261295.434±163506μm3,总表面积左右分别为386038.301±1670和386610.607±941μm2,轴比左肾为0.85,右肾为0.86;②对照组小鼠肾脏总体积左右分别为11779367.918±106141和11261191.984±134263μm3,总表面积左右分别为386012.104±678和386409.907±584μm2,轴比左右均为0.85;③实验组小鼠肾脏总体积左右分别为9770964.044±107921和10211541.613±106863μm3,总表面积左右分别为318097.638±1270和327367.436±310μm2,轴比左右均为0.85,均明显小于正常及对照组。正常及对照组小鼠肾脏体积、表面积比较无统计学差异(P>0.05),但与实验组比较均有统计学差异(P< 0.05)。
结论:1.应用组织器官系统整体原位固定、连续组织切片对新生小鼠肾脏进行三维重建可行性好,它不仅能重建该器官的整体形态结构,而且可获得较精确的形态学参数。2.应用组织器官系统整体原位固定、连续组织切片三维重建的方法可辩别器官细微的整体形态变化,这对于传统的肉眼观察具有不可比拟的优势。3.孕期暴露DES可引起雄性新生小鼠肾脏体积缩小。4.应用组织器官系统整体原位固定、连续组织切片对新生小鼠肾脏进行三维重建的方法将为更为复杂、精细的泌尿生殖系统形态学量化研究奠定基础。
Objective:In the half century,the mechanisms of congenital abnormalities studies were advanced quickly,the animal models of congenital abnormalities have been made successly.However, in the old study,whether there were abnormalities and how about the degrees mainly depended on manual watch and measure ,such as,the location of testis,the weight of genital organs,the distance of anus and genitals,the separation of prepuce,etc. Because these results were acquired by different observer,they were not consistent frequently,and it is difficult to confirm the malformation accurately,the study of malformation morphology advance slowly.The computer three-dimensonal reconstruction can reconstruct the organs by serial slices,and calculate the length、volume、area of organs,it is the most important to avoid the manual error.In this study,the kidneise of newborn mice were reconstructed by serial slices,and calculate their volume and area,hope to find elaborate method to evaluate urogenital system malformations.
Materials and methods:30 8-10 weeks old Kunming female mice were divided into three groups randomly,that is :normal group(not given any drug),contral group (given DMSO and NS),and experimental group(DES was given 100ug/kg/d).Pregnant mice were injected subcutaneously from GD9(gestation day)to GD17.The newborn mice,when they were delivered, were collected at once for the determination of sexuality.And then,five male mice of them were randomly selected from each group.All the selected newborn mice were treated as follows:the low parts of abdomen were fixed in situ and set to transected serial slice.All the slices(HE prepared and 5μm thick) were studied under microscopy and recorded serially in JPG form.The 3D-reconstruction were being made by the soft of Photoshop 8.0.1 and CATIAV6.
Result:1.The volume of newborn mice in normal and control groups are bigger than the experimental group obviously,but the size of kidneies are very difficult to distinguish by dissection observation in all groups.2. In the serial transects of normal newborn mice, the kidney were all in round shape and the curves were smooth,and they have only one renal papilla,the glumerular and tubular were well developed.There were no difference in the other two groups.3.After 3D-reconstruction,the 3D picture of kidney and some morphologicalparameters were acquired:①In the normal group,the volume of left and right kidney was about 11778477.518±181412and 11261295.434±163506μm3respectively;the area of left and right kidney was about 386038.301±1670and 386610.607±941μm2respectively,the ratio of long-short axis of left kidney was 0.85,and the right kidney was 0.86.②In the control group, the volum e of left and right kidney was about 11779367.918±106141and 11261191.984±134263μm3 respectively;the area of left and right kidney was about 386012.104±648 and 386409.907±584μm2respectively , the ratios of long-short axis were all 0.85.③In the experimental group, the volume of left and right kidney was about9770964.044±107921and 10211541.613±106863μm3respectively; the area of left and right kidney was about 318097.638±1270 and 327367.436±310μm2 respectively,the ratios of long-short axis were all 0.85.The volume and area of kidney were all smaller obviously than that of normal and control groups(P< 0.05).
Conclusion:1.Method of reconstructing the 3D picture of newborn mice kidney with serial tissue sections is feasible. It not only can reconstruct the 3D picture of newborn mice kidney,but also acquire precise morphology parameter.2.Method of reconstructing the 3D picture with serial tissue sections can distinguish the fine difference of the tiny organ morphology,it is better than manual observation.3.Exposure to DES make the newborn mice kidney smaller.4.The method of reconstructing the 3D picture of newborn mice kidney with serial tissue sections is the foundation of urogenital system 3D-reconstruction.
引文
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