脂多糖致大鼠肾小管慢性炎症模型的探究

A study on lipopolysaccharide-induced renal tubular chronic inflammation model in rats

目的:通过尾静脉注射脂多糖(Lipopolysaccharide,LPS)不同剂量以及不同周期探究肾小管慢性炎症大鼠模型的合适给药剂量以及周期。方法:无特定病原体动物级雄性SD大鼠63只,按照随机原则分为9组:正常组、0.41组(0.4 mg/kg剂量给药1周)、0.42组(0.4 mg/kg剂量给药2周)、0.43组(0.4 mg/kg剂量给药3周)、0.44组(0.4 mg/kg剂量给药4周)、0.21组(0.2 mg/kg剂量给药1周)、0.22组(0.2 mg/kg剂量给药2周)、0.23组(0.2 mg/kg剂量给药3周)、0.24组(0.2 mg/kg剂量给药4周)。每一周期结束,将相应周期0.4 mg/kg组以及0.2 mg/kg组大鼠麻醉取血,检测外周血中白细胞总数、淋巴细胞比例、中性粒细胞比例、单核细胞比例和血清中超敏C-反应蛋白(High-sensitivity C-reactiveprotein,hs-CRP)、白细胞介素-1(Interleukin-1,IL-1)以及肿瘤坏死因子-α(Tumor Necrosis Factor-α,TNF-α)水平的变化;取肾脏组织,在光镜下观察肾脏病理改变。结果:与正常组比较,尾静脉注射脂多糖1周即已开始出现炎症细胞的增多以及肾脏组织炎症细胞的浸润,随着给药次数增加,炎症细胞的水平均逐渐升高,4周时0.4 mg/kg组肾脏组织出现结缔组织的增生。同一周期内,0.4 mg/kg组炎症细胞水平的升高更加明显。结论:0.4 mg/kg剂量脂多糖尾静脉给药4周可成功复制肾小管慢性炎症大鼠动物模型。

Objective:To investigate the appropriate dose and cycle of renal tubular chronic inflammation rat model through different doses and cycles of injection of lipopolysaccharide at the tail vein.Methods:There were 63 male SD rats in SPF grade,and they were divided into 9 groups:the normal group,the 0.41 group(0.4 mg/kg dose administration for 1 week),the 0.42 group(0.4 mg/kg dose administration for 2 weeks),the 0.43 group(4 mg/kg dose administration for 3 weeks),the 0.44 group(0.4 mg/kg dose administration for 4 weeks),the 0.21 group(0.2 mg/kg dose administration for 1 week),the 0.22 group(0.2 mg/kg dose administration for 2 weeks),the 0.23 group(3 weeks of administration at 0.2 mg/kg dose)and the 0.24 group(4 weeks of administration at 0.2 mg/kg dose).At the end of each cycle,the rats in the 0.4 mg/kg group and 0.2 mg/kg group of the corresponding cycle were collected to detect the total number of white blood cells,lymphocyte proportion,neutrophil ratio,mononucleocyte ratio,hypersensitivity C-reactive protein,interleukin-1,and tumor necrosis factor-αlevels.The pathological changes of kidney tissue were observed under light microscope.Results:Compared with the normal group,the increase of inflammatory cells and the infiltration of inflammatory cells in kidney tissue began to appear after 1 week of tail vein injection of lipopolysaccharide.The levels of inflammatory cells were gradually increased with the increase of administration times,and the hyperplasia of connective tissue appeared in the kidney tissue in the 0.4 mg/kg group at 4 weeks.During the same cycle,the level of inflammatory cells was increased more significantly in the 0.4 mg/kg group.Conclusion:The 0.4 mg/kg dose of lipopolysaccharide administered by tail vein for 4 weeks can successfully replicate the rat animal model of chronic renal tubular inflammation.