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

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