草酸钙型肾结石小鼠模型的研究

摘要

目的：摸索简单易行的方法诱导草酸钙型肾结石小鼠模型，为后续药效学研究提供可靠的动物模型。方法：将健康小鼠分为正常组（A组）、模型组（B组）、模型组（C组），B组灌胃给予诱石剂（含0.75％乙二醇和0.75％氯化铵的水溶液），C组灌胃给予诱石剂（含1％乙二醇和1％氯化铵的水溶液），1 mL／次，3次／d，连续28 d进行造模，A组平行灌胃给予等量生理盐水。实验期间观察小鼠的进食进水情况，生命体征，行为活动及体毛变化，于造模后7、14、21、28 d收集24 h尿液进行草酸和钙含量的测定，于末次造模后处死小鼠，剖取肾脏进行病理学观察。结果：于造模第3天开始，B、C组小鼠均出现后肢无力爬行，食欲减退，体毛呈进行性晦暗无光泽，C组小鼠的表现比B组小鼠严重；造模7 d后，模型组开始出现不同数量的动物死亡，且C组死亡率高于B组；B组和C组小鼠尿液中草酸、钙浓度均明显高于A组（P＜0.01），B组尿草酸浓度明显高于C组（P＜0.05～0.01），而尿钙浓度明显低于C组（P＜0.01）；病理学结果表明，A组小鼠肾小管未见扩张和草酸钙晶体沉积，B组、C组小鼠肾组织均出现肿胀，肾小管管腔明显扩张、变性、坏死，肾间质有明显慢性炎性细胞浸润，表面点状分布白色结晶或钙化，在近曲小管和远曲小管有大片结晶存在，且B组的成石率比模型C组高。结论：采用0.75％乙二醇及0.75％的氯化铵混合溶液作为诱石液，可成功诱导死亡率低、成石率高的草酸钙型肾结石小鼠模型。%Objective:To explore a method of establishing mice model with calcium-oxalate kidney stones so as to provide the reli-able animal models for follow-up study on pharmacodynamics .Methods: Mice were divided to normal group ( A group ) , model group (B group) and model group (C group) randomly.0.75%ethylene glycol and 0.75% ammonia chloride mixture were ad-ministrated orally1 mL/time and 3 times/day to B group mice for 28 consecutive days .1%ethylene glycol and 1%ammonia chlo-ride mixture were administrated orally to C group mice as well as B group .The same volume of normal saline was administered in parallel to A group.Food and water intake, vital signs, behavior and change of hair were observed in experiment .24 h urine of mouse was collected for detecting concentration of oxalic acid and calcium at 7, 14, 21, 28 days after modeling.All of mice were sacrificed at the last time , and took the kidney to carry out pathological observation .Results:The phenomenon of inability to crawl on the hind legs , loss of appetite and the dull hair were observed in B and C group mice after modeling 3 days.The situation of C group was more serious than B group .The model animals began to die after modeling 7 days and the mortality rate of C group was higher than that of group B .The concentration of oxalic acid and calcium in urine of B group or C group were more than A group (P<0.01).The concentration of oxalic acid in B group was significantly higher than that in C group (P<0.05~0.01), but the calcium concentration was significantly lower than that of the C group ( P<0.01 ) .No abnormalities and Calcium oxalate crystal were found in the kidney of A group mice .In B and C groups , the renal tissues of mice were swollen .The renal tubular lumen showed obvious expansion , degeneration necrosis and there was obvious chronic inflammatory cell infiltration in renal interstitial . The surface of the kidney is dotted with white crystals or calcification .There are large tracts of crystal in the proximal and distal tu-bules and Number of crystals in B group was more than that in C group .Conclusion:It was found that 0.75%ethylene glycol and 0.75%ammonia chloride mixture can be successfully induced low mortality , high stone rate of calcium oxalate kidney stones in mice.