Wistar大鼠肾结石形成过程的动态观察研究

doi:10.3969/j.issn.1007-9572.2018.00.234

摘要/Abstract

摘要： 目的　观察Wistar大鼠肾结石形成的动态过程。方法　2016年3月选取6周龄左右SPF级雄性Wistar大鼠60只，适应性饲养1周后随机分为空白对照组（NC组，n=30）和乙二醇组（EG组，n=30）。NC组大鼠正常饮水，2 ml 0.9%氯化钠溶液灌胃2周；EG组大鼠饮用1% EG溶液，2 ml 2%氯化铵溶液灌胃2周。连续10周观察两组大鼠一般情况，每周处死3只，每周检测两组大鼠血、尿生化指标，肉眼及解剖显微镜下观察大鼠肾脏解剖情况，并分析两组大鼠肾脏结晶分级及结石形成情况。结果　观察期间EG组大鼠垫料有血尿，造模期间于第8周死亡1只，第9周死亡1只。造模1~2周时两组大鼠进食良好、安静温顺。造模3~8周时，NC组大鼠无特殊表现，EG组大鼠表现为烦躁兴奋、活泼好动。造模9~10周EG组大鼠表现为精神疲倦，针刺反应迟钝，活动度减少，食量减少；NC组大鼠无特殊表现。EG组大鼠造模第2~10周血肌酐、血尿酸均高于NC组（P<0.05）。EG组大鼠第3~8周尿素氮高于NC组（P<0.05）。EG组大鼠第2周、第4~10周尿钙高于NC组（P<0.05）。EG组大鼠第5~10周血钙高于NC组（P<0.05）。EG组大鼠第6~10周血磷、血镁高于NC组（P<0.05）。EG组大鼠第2~8周尿pH值低于NC组（P<0.05）。两组大鼠第1~10周尿比重、尿量比较，差异无统计学意义（P>0.05）。EG组大鼠第3~10周肾体比高于NC组（P<0.05）。造模第1~2周，肉眼观察两组大鼠肾脏无明显差异。造模第3周开始，肉眼观察EG组大鼠部分肾脏较NC组略有增大。造模第6周以后，肉眼观察EG组大鼠肾脏肿大；解剖显微镜下可见晶体以肾盂为中心呈扇形分布。造模第6周以后，肉眼观察NC组大鼠肾脏表面光滑，解剖显微镜下亦未见明显结晶。EG组大鼠肾脏结晶分级高于NC组（Z=-5.195，P<0.001）。EG组大鼠结石检出率高于NC组（χ2=21.172，P<0.001）。结论　采用EG加氯化铵法建立的肾结石模型大鼠在造模第3周开始形成结石，肾结石模型大鼠明显较空白对照大鼠精神疲倦，活动度及饮食量减少，血、尿生化指标明显改变，肾体比明显升高。

关键词: 肾结石, 乙二醇, Wistar大鼠, 动物模型建立

Abstract: Objective　To observe the dynamic process of kidney stone formation in Wistar rats.Methods　In March 2016，60 6-week-old SPF male Wistar rats were selected and randomly divided into a normal control（NC） group（n=30） and an ethylene glycol（EG） group（n=30） after 1 week of adaptive breeding.Rats in the NC group were administered a normal amount of drinking water with 2 ml 0.9% sodium chloride by gavage for 2 weeks.Rats in the EG group were administered 1% EG solution with 2 ml 0.9% sodium chloride by gavage for 2 weeks.The general condition of the rats in the two groups was observed for 10 consecutive weeks.Three rats were sacrificed every week.Blood and urine biochemical indicators were measured in both of the groups every week，and the anatomy of the kidneys of the rats was observed with the naked eye and under a dissection microscope.The renal crystallization grade and stone formation were analyzed in both groups.Results　During the observation period，the rats in the EG group exhibited hematuria.One rat died in the 8th week，and another died in the 9th week during the model establishment period.After 1 to 2 weeks of modeling，the rats in both groups were well fed，quiet and docile.After 3 to 8 weeks of modeling，there was no behavioral changes in the NC group，but the rats in the EG group were irritated and lively and active.After 9 to 10 weeks of modeling，the rats in the EG group exhibited mental fatigue，attenuated reactions to acupuncture，reduced activity and reduced food intake，whereas the rats in the NC group showed no behavioral changes.The serum creatinine and serum uric acid were higher in the EG group than in the NC group after 2 to 10 weeks of modeling（P<0.05）.The urea nitrogen was higher in the EG group than in the NC group in the 3rd to 8th week（P<0.05）.The urinary calcium in the EG group was higher than that in the NC group in the 2nd and 4th-10th weeks（P<0.05）.The blood calcium was higher in the EG group than in the NC group in the 5th to 10th week（P<0.05）.The phosphorus and magnesium levels were higher in the EG group than the NC group in the 6th to 10th week（P<0.05）.The urinary pH value of rats in the EG group was lower than that in the NC group（P<0.05）.There were no significant differences in urine specific gravity and urine volume between the two groups（P>0.05）.The ratio of kidney volume was higher in the EG group than the NC group in the 3rd to 10th week，and the difference was statistically significant（P<0.05）.After 1 to 2 weeks of modeling，no significant differences were observed in the kidney between the two groups.After the third week of modeling，the kidneys in the EG group were slightly larger than those in the NC group.After the 6th week of modeling，the kidney enlargement of the rats in the EG group was visible to the naked eye.Under a dissecting microscope，the crystals were found to be distributed in a fan-like shape centered on the renal pelvis.After the 6th week of modeling，the surfaces of the kidneys in the NC rats was observable with the naked eye，and no obvious crystallization was observed under a dissection microscope.The renal crystallization fraction of rats in the EG group was higher than that in the NC group（Z=-5.195，P<0.001）.The incidence of kidney stones in the EG group was higher than that in the NC group，and the difference was statistically significant（χ2=21.172，P<0.001）.Conclusion　A rat kidney stone model established by administration of ethylene glycol（EG） began to form stones in the 3rd week of modeling.Compared with the NC rats，the rats with kidney stones were prone to mental fatigue，decreased activity and dietary intake，marked changes in blood and urine biochemical indicators，and a significantly increased kidney-body ratio.

Key words: Kidney calculi, Ethylene glycol, Wistar rats, Animal model establishment

钱成,王勤章,褚浩,等. Wistar大鼠肾结石形成过程的动态观察研究[J]. 中国全科医学, 2018, 21(27): 3343-3348. DOI: 10.3969/j.issn.1007-9572.2018.00.234.
QIAN Cheng,WANG Qin-zhang,CHU Hao, et al. Dynamic Observation of Kidney Stone Formation in Wistar Rats[J]. Chinese General Practice, 2018, 21(27): 3343-3348. DOI: 10.3969/j.issn.1007-9572.2018.00.234.

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