连续中毒剂量维生素D_3对大鼠肾组织结构的影响
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摘要
目的探讨中毒剂量维生素D_3(VitaminD_3,VD_3)对大鼠肾组织病理切片和超微结构的影响。方法将健康SD大鼠随机分为空白对照组、VD_3小剂量组(1875 IU/kg)、VD_3中剂量组(3750 IU/kg)、VD_3大剂量组(7500 IU/kg)、VD_3超大剂量组(15 000 IU/kg),每组8只,连续给药3周后,观察大鼠肾组织病理切片和肾组织超微结构变化。结果光镜下病理切片观察,空白对照组大鼠肾组织结构清晰、完整,肾小球与肾小管及肾小管上皮细胞均未见异常;VD_3各剂量组近曲肾小管上皮组织细胞均发生了不同程度改变,主要表现为近曲小管上皮细胞肿胀、变性,管腔变小,出现管型等,偶见间质增生,中性粒细胞、巨噬细胞等炎症细胞浸润等,以大剂量组最明显。透射电子显微镜下观察肾组织超微结构显示,空白对照组足突、基膜和毛细血管内皮细胞、窗孔结构无明显异常,毛细血管管腔内透明;小剂量组基膜厚薄不均,毛细血管管腔内不透明,布满颗粒状物;中剂量组基膜增厚,毛细血管管腔内出现吞饮小泡;大剂量组足突部分融合,基膜增厚改变典型,内皮细胞分界不清;超大剂量组足细胞的足突和基膜、内皮细胞分界不清,融合在一起,两侧完整,出现内皮吞饮小泡,毛细血管管腔内有两个大小不等的圆形均质体,细胞器结构清晰。结论 7500 IU/kg中毒剂量VD_3可造成实验大鼠明显毒性反应,是建立实验大鼠中毒模型的推荐剂量。
Objective To investigate the toxic effects of vitamin D_3(VD_3) on ultrastructure renal tissue sections of adult rats. Methods Healthy SD rats were randomly divided into blank control group,VD_3 low-dose group(1875 IU/kg), VD_3 high-dose group(3750 IU/kg),VD_3 high-dose group(7500 IU/kg) and VD_3 ultra-high-dose group(15,000 IU/kg). Eight rats in each group were given VD_3 for 3 weeks. The pathological sections and ultrastructural changes of kidney tissues were observed. Results Histological observation under light microscopy showed that the renal tissue structure of rats in the blank control group was clear and intact,and there were no abnormalities in glomeruli, tubules and tubular epithelial cells. The epithelial cells of proximal convoluted tubules changed in varying degrees in VD_3 dose groups, mainly manifested as swelling and degeneration of proximal convoluted tubular epithelial cells and small lumen. Tube type,interstitial hyperplasia,infiltration of inflammatory cells such as neutrophils and macrophages were found occasionally in the high dose group. The ultrastructure of kidney tissue under transmission electron microscopy showed that there were no obvious abnormalities in the foot process,basement membrane,capillary endothelial cells and window pore structure in blank control group, and the capillary lumen was transparent; the basement membrane was uneven in low dose group,and the capillary lumen was opaque and full of granules;the basement membrane was thickened and capillary in medium dose group. In the vascular lumen, swallowing vesicles appeared;in the high-dose group, the foot processes fused partially, the basement membrane became thicker and the boundary between endothelial cells was not clear; in the ultra-high-dose group,the foot processes and basement membrane and endothelial cells were not clearly demarcated,fused together, both sides were intact, endothelial swallowing vesicles appeared, and there were two different sizes in the capillary lumen. Round homogeneous body with clear organelle structure. Conclusions The toxic dose VD_3 of 7500 IU/kg can cause obvious toxic reaction in experimental rats. It is the recommended dose for establishing toxic model in experimental rats.
Objective To investigate the toxic effects of vitamin D_3(VD_3) on ultrastructure renal tissue sections of adult rats. Methods Healthy SD rats were randomly divided into blank control group,VD_3 low-dose group(1875 IU/kg), VD_3 high-dose group(3750 IU/kg),VD_3 high-dose group(7500 IU/kg) and VD_3 ultra-high-dose group(15,000 IU/kg). Eight rats in each group were given VD_3 for 3 weeks. The pathological sections and ultrastructural changes of kidney tissues were observed. Results Histological observation under light microscopy showed that the renal tissue structure of rats in the blank control group was clear and intact,and there were no abnormalities in glomeruli, tubules and tubular epithelial cells. The epithelial cells of proximal convoluted tubules changed in varying degrees in VD_3 dose groups, mainly manifested as swelling and degeneration of proximal convoluted tubular epithelial cells and small lumen. Tube type,interstitial hyperplasia,infiltration of inflammatory cells such as neutrophils and macrophages were found occasionally in the high dose group. The ultrastructure of kidney tissue under transmission electron microscopy showed that there were no obvious abnormalities in the foot process,basement membrane,capillary endothelial cells and window pore structure in blank control group, and the capillary lumen was transparent; the basement membrane was uneven in low dose group,and the capillary lumen was opaque and full of granules;the basement membrane was thickened and capillary in medium dose group. In the vascular lumen, swallowing vesicles appeared;in the high-dose group, the foot processes fused partially, the basement membrane became thicker and the boundary between endothelial cells was not clear; in the ultra-high-dose group,the foot processes and basement membrane and endothelial cells were not clearly demarcated,fused together, both sides were intact, endothelial swallowing vesicles appeared, and there were two different sizes in the capillary lumen. Round homogeneous body with clear organelle structure. Conclusions The toxic dose VD_3 of 7500 IU/kg can cause obvious toxic reaction in experimental rats. It is the recommended dose for establishing toxic model in experimental rats.
引文
[1]窦晓娟,汪求真,韩孝红,等.大剂量维生素D3补充对糖尿病大鼠淋巴细胞增殖活性的影响[J].中国药理学通报,2016,32(4):589-590.
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[4]杨文彬,李百强,史向华,等.维生素D3低剂量连续给药对大鼠肾脏超微结构的变化[J].山西医药杂志,2017,46(3):271-273.
[5]林岚,彭静宜,谭美珍,等.69例维生素D过量病例的血清维生素D与钙及钙磷乘积的关系[J].国际医药卫生导报,2017,23(12):1862-1865.
[6]朱庆龄,盛晓阳.维生素D过量及中毒的研究进展[J].中华儿科杂志,2015,53(3):235-237.
[7]Alshahrani F,Aljohani N.Vitamin D:deficiency,sufficiency and toxicity[J].Nutrients,2013,5(9):3605-3616.
[8]张会丰,韩笑,武姗姗.血清25(OH)D水平对评估儿童维生素D营养状况的意义和界值[J].中华儿科杂志,2015,53(3):164-167.
[9]黄昭穗,王贵国,陈琼华,等.维生素D中毒致急性肾损伤[J].中华肾脏病杂志,2010,26(5):375.
[10]Jones G.Pharmaeokinetics of vitamin D toxicity[J].Am J Clin Nutr,2008,88(2):582S-586S.
[2]谢顺英,罗炎姣.儿童营养性维生素D缺乏性佝偻病合并缺铁性贫血的临床分析[J].中国药物经济学,2015,10(S1):238-239.
[3]Nebbioso M,Buomprisco G,Pascarella A,et al.Modulatory Effects of 1,25-dihydroxyvitamin D3 on Eye Disorders:A Critical Review[J].Crit Rev Food Sci Nutr,2017,57(3):559-565.
[4]杨文彬,李百强,史向华,等.维生素D3低剂量连续给药对大鼠肾脏超微结构的变化[J].山西医药杂志,2017,46(3):271-273.
[5]林岚,彭静宜,谭美珍,等.69例维生素D过量病例的血清维生素D与钙及钙磷乘积的关系[J].国际医药卫生导报,2017,23(12):1862-1865.
[6]朱庆龄,盛晓阳.维生素D过量及中毒的研究进展[J].中华儿科杂志,2015,53(3):235-237.
[7]Alshahrani F,Aljohani N.Vitamin D:deficiency,sufficiency and toxicity[J].Nutrients,2013,5(9):3605-3616.
[8]张会丰,韩笑,武姗姗.血清25(OH)D水平对评估儿童维生素D营养状况的意义和界值[J].中华儿科杂志,2015,53(3):164-167.
[9]黄昭穗,王贵国,陈琼华,等.维生素D中毒致急性肾损伤[J].中华肾脏病杂志,2010,26(5):375.
[10]Jones G.Pharmaeokinetics of vitamin D toxicity[J].Am J Clin Nutr,2008,88(2):582S-586S.