Abstract: Objective　To investigate the inhibiting effects of vitamin receptor agonist-parlicalcitol on the inflammatory reaction of kidney tissue in diabetic nephropathy mice by exploiting the db/db mouse model of type 2 diabetic nephropathy.Methods　From January to November in 2015，under the method of random number table，we divided the 60 male five-week C57BLKS/J db/db mice of SPF level into three groups：db/db-control group（N group，n=20），db/db-dimethyl sulfoxide group（D group，n=20），and db/db-paricalcitol group（P group，n=20），and we enrolled db/m mice of littermate as the normal control group（C group，n=20）.At the age of 10 weeks，mice in P group were given intraperitoneal injection of paricalcitol at a dose of 0.3 μg/kg qod，the same amount of dimethyl sulfoxide as P group plus 0.9% sodium chloride solution were injected into D group，N and C group were not intervened.After 12-week intervention，we measured the body mass index，the fasting blood-glucose，24-hour urine protein quantitation；we retained the kidney tissue to make a renal histopathological examination.The expression of real-time fluorescent quantitative PCR，Western blotting，and immunohistochemical detection of inflammatory factor interleukin（IL）-6，and tumor necrosis factor-α（TNF-α）mRNA and the protein expression levels were applied.Results　After 12-week medical intervention，the comparison of body mass，fasting blood-glucose，and the 24-hour urine protein quantitation in the four groups showed significant differences（P<0.01）；the body mass，fasting blood-glucose，the 24-hour urine protein quantitation of N group，D group and P group were higher than those of C group，the 24-hour urine protein quantitation of P group was lower than that of N group and D group（P<0.05）.Pathological examination showed that the structure of the glomerulus and the renal tubular of C group was complete and clear；while there was partially inflammatory cell infiltration in renal tubulointerstitial in subjects of N group and D group，the inflammatory reaction was evident compared with C group；compared with N group and D group，the renal pathologic changes of P group reduced，and the inflammatory reaction alleviated.The IL-6，TNF-α mRNA and the protein expression level of the four groups were significantly different（P<0.01）；the expression levels of IL-6，TNF-α mRNA and protein of N group，D group and P group were all higher than those of C group，and the expression levels of IL-6，TNF-α mRNA and protein of P group were lower than those of N group and D group（P<0.05）.Immunohistochemical results showed that compared with C group，the renal tissue expression of IL-6，TNF-α of N group and D group increased，and those of P group decreased compared with N group and D group.Conclusion　Paricalcitol can alleviate the inflammatory reaction in diabetic nephropathy mice kidney tissue，and the effect may not rely on reducing blood glucose.

Key words: Diabetic nephropathies, Paricalcitol, Interleukin-6, Tumor necrosis factor-alpha

摘要： 目的　利用2型糖尿病肾病db/db小鼠模型，探讨维生素受体激动剂帕立骨化醇对糖尿病肾病小鼠肾组织炎性反应的抑制作用。方法　2015年1—11月，将60只雄性5周龄SPF级C57BLKS/J db/db小鼠采用随机数字表法分为db/db-对照组（N组，n=20）、db/db-二甲基亚砜组（D组，n=20）、db/db-帕立骨化醇组（P组，n=20），同窝出生的db/m小鼠作为正常对照组（C组，n=20）。10周龄时P组小鼠腹腔注射0.3 μg/kg帕立骨化醇，隔日1次，D组小鼠腹腔注射与P组等量的二甲基亚砜+0.9%氯化钠溶液，N组和C组小鼠不做处理。干预12周后测定小鼠体质量、空腹血糖、24 h尿蛋白定量；留取肾组织并进行肾组织病理学检查。应用实时荧光定量PCR、Western blotting和免疫组化检测炎性因子白介素（IL）-6、肿瘤坏死因子α（TNF-α）mRNA及其蛋白的表达水平。结果　干预12周后，4组小鼠体质量、空腹血糖水平、24 h尿蛋白定量比较，差异均有统计学意义（P<0.01）；其中N组、D组和P组小鼠体质量、空腹血糖水平和24 h尿蛋白定量高于C组，P组小鼠24 h尿蛋白定量低于N组和D组（P<0.05）。病理学检查显示：C组肾小球及肾小管结构完整清晰；N组和D组可见肾小管间质局部炎性细胞浸润，与C组比较，炎性反应明显；P组肾脏病理改变较N组和D组减轻，炎性反应减轻。4组IL-6、TNF-α mRNA及其蛋白表达水平比较，差异均有统计学意义（P<0.01）；其中N组、D组、P组IL-6、TNF-α mRNA及其蛋白表达水平均高于C组，P组IL-6、TNF-α mRNA及其蛋白表达水平均低于N组和D组（P<0.05）。免疫组化结果显示，与C组比较，N组和D组肾组织IL-6、TNF-α表达上调；而P组肾组织IL-6、TNF-α表达较N组和D组下调。结论　帕立骨化醇可减轻糖尿病肾病小鼠肾组织炎性反应，且该作用可能不依赖于降糖。

关键词: 糖尿病肾病, 帕立骨化醇, 白细胞介素6, 肿瘤坏死因子α