首页|不同剂量腺嘌呤建立脾肾阳虚型慢性肾衰竭大鼠模型的实验研究

不同剂量腺嘌呤建立脾肾阳虚型慢性肾衰竭大鼠模型的实验研究

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目的 比较不同剂量腺嘌呤灌胃对模型大鼠一般状态、生化指标及肾脏病理组织的影响,确定腺嘌呤灌胃制备脾肾阳虚型慢性肾衰竭(Chronic kidney disease,CRF)大鼠模型的最佳造模剂量.方法 将24只SD雄性大鼠随机分为正常组与模型组,模型组大鼠分为Ml组、M2组和M3组,每组6只.正常组给予等量生理盐水灌胃,Ml组以腺嘌呤150 mg·kg-1·d-1灌胃、M2组以腺嘌呤200 mg·kg-1·d-1灌胃,M3组以腺嘌呤300 mg·kg-1·d-1灌胃.连续干预3周,造模前及造模后每周检测肌酐(Serum creatinine,Scr)、尿素氮(Blood urea nitrogen,BUN)、24 h 尿蛋白定量(24-hour urinary protein quantification,24 h-UTP)水平,3 周后取肾脏病理组织采用苏木-伊红(HE)和马松(Masson)染色法对大鼠肾脏组织病理学进行模型评估.结果 与正常组大鼠比较,模型组大鼠均出现不同程度的精神萎靡不振,活动度降低,弓背蜷缩,毛发稀疏无光泽,耳缘及脚趾苍白发凉,小便频数,大便稀溏等现象.与正常组大鼠比较,各模型组大鼠体重均有不同程度的减轻(P<0.05),造模第2周,与M1组大鼠体重比较,M2组、M3组大鼠差异均有统计学意义(P<0.05).与正常组大鼠比较,各模型组大鼠24 h尿量明显增多(P<0.05),Scr、BUN及24 h-UTP水平均升高(P<0.05),且M3组大鼠各指标升高最明显.各模型组大鼠Scr、BUN及24 h-UTP比较差异均有统计学意义(P<0.05).肾脏病理染色结果显示各模型组大鼠的肾脏组织出现不同程度的改变,镜下见肾小球形态基本完整,部分肾小球结构破坏;部分近肾小管空泡变性严重,上皮萎缩,部分肾小管管腔扩张,管腔内见红染无结构的蛋白管型样物及较多红细胞;随着腺嘌呤灌注剂量增加,肾小球内可见大量黄绿色结晶沉淀物,存在肾间质炎性细胞浸润和纤维组织增生.结论 腺嘌呤灌胃可成功建立脾肾阳虚型慢性肾衰竭动物模型,其中200 mg·kg-1·d-1灌胃组更接近临床脾肾阳虚型慢性肾衰竭发展进程,且死亡率较低,符合脾肾阳虚型慢性肾衰竭生理病理学特点.
Experimental study of different doses of adenine to establish a rat model of chronic renal failure with spleen-kidney Yang-deficiency
Objective To compare the effects of different doses of adenine gavage on the general state,bio-chemical indicators and renal pathological tissue of the model rats,and determine the optimal dosage of ad-enine to prepare the rat model of chronic kidney disease(CRF)with spleen-kidney-Yang deficiency.Meth-ods 24 SD male rats were randomly divided into normal group and model group,and the model group rats were divided into M1 group,M2 group and M3 group,with 6 rats in each group.In the normal group giv-ing the same amount of normal saline gavage,M1 group was gavaged with adenine 150 mg·kg-1·d-1,M2 group was gavaged with adenine 200 mg·kg-1·d-1,and M3 group was gavaged with adenine 300 mg·kg-1·d-1.After 3 weeks of serum creatinine(Scr),blood urea nitrogen(BUN),and 24-hour urinary protein quantification(24 h-UTP)levels were detected before and every week after molding,and renal pathological tissues were taken after 3 weeks to model the renal histopathology of rats by hematoxy-eosin(HE)and Masson staining.Results Compared with normal group of the rats,model group of the rats showed varying degrees of mental depression,decreased mobility,hunched back,sparse and dull hair,pale and cool ear and toe edges,frequent urination and loose stools.Compared with normal group of rats,each model group showed varying degrees of weight reduction(P<0.05).At the second week of modeling,compared with M1 group of the rats,there were statistically significant differences in weight between the M2 and M3 groups(P<0.05).Compared with normal group of the rats,24-hour urine out-put of each model group rats was significantly increased(P<0.05),and the levels of Scr,BUN,and 24-hour UTP were all increased(P<0.05),with M3 group rats showing the most significant increase in va-rious indicators.The differences in Scr,BUN and 24 h UTP among the different model groups of the rats were statistically significant(P<0.05).The results of renal pathological staining showed that the renal tissue of the rats in each model group changed to varying degrees.Microscopically,the glomerular mor-phology was basically complete and some glomerular structures were destroyed.Some proximal renal tu-bules had serious vacuolar degeneration,epithelial atrophy,some renal tubules had dilated lumen,and there were many red blood cells in the lumen.With the increasing of adenine perfusion dose,a large num-ber of yellow-green crystalline precipitates can be seen in glomerulus,and there were inflammatory cell in-filtration and fibrous tissue hyperplasia in renal interstitial.Conclusion Adenine gavage can successfully establish an animal model of spleen-kidney Yang deficiency chronic renal failure,among which the 200 mg·kg-1·d-1 gavage group is closer to the development process of clinical spleen-kidney-Yang defi-ciency chronic renal failure,and the mortality rate is low,which is in line with the physiological and path-ological characteristics of spleen-kidney-Yang deficiency chronic renal failure.

chronic renal failurespleen and kidney Yang deficiencyadenineanimal models

刘晓、李悦、李静茹、陆蕾、谢娜、朱慧敏、舒占钧

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新疆医科大学第四临床医学院,乌鲁木齐 830099

新疆医科大学附属中医医院中医药临床研究基地,乌鲁木齐 830099

慢性肾衰竭 脾肾阳虚 腺嘌呤 动物模型

新疆维吾尔自治区创新环境(人才、基地)建设专项项目

2022D04075

2024

新疆医科大学学报
新疆医科大学

新疆医科大学学报

CSTPCD
影响因子:0.76
ISSN:1009-5551
年,卷(期):2024.47(2)
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