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作 者:邹敏书[1] 余健[1] 聂国明 尹晓玲[2] 周建华[2]
机构地区:[1]广州军区武汉总医院儿科,湖北武汉430070 [2]华中科技大学同济医学院同济医院儿科,湖北武汉430030
出 处:《临床儿科杂志》2013年第9期871-875,共5页Journal of Clinical Pediatrics
基 金:国家自然科学基金面上项目(NO.81070557)
摘 要:目的探讨维生素D(VitD)在IgA肾病(IgAN)发病机制中的作用。方法 BALB/C小鼠诱导IgAN模型并随机分为IgAN组(n=15),IgAN+VitD组(n=15),分别给予丙二醇以及丙二醇+1,25(OH)2D 3 ng/(100g·d),连续6周;另设对照组(n=15)。第0、12、18周,测定各组小鼠24 h尿蛋白;第18周测定血清25(OH)D、成纤维细胞生长因子23(FGF23)及半乳糖缺乏IgA1(Gd-IgA1)水平;荧光定量RT-PCR及Western blot检测Peyer小结白介素-21(IL-21)mRNA及蛋白,Bcl-6蛋白表达;流式细胞测定Peyer小结Tfh细胞占T淋巴细胞,B220+IgM+、B220+IgA+、B220-IgA+淋巴细胞占B淋巴细胞百分率。结果与对照组相比,IgAN组小鼠24 h尿蛋白升高;血清25(OH)D降低,FGF23及Gd-IgA1升高;Peyer小结IL-21 mRNA和蛋白,Bcl-6蛋白表达升高;Peyer小结Tfh细胞占T细胞百分率,B220+IgM+、B220+IgA+、B220-IgA+淋巴细胞占B淋巴细胞百分率升高,差异均有统计学意义(P均<0.05);IgAN+VitD组各项指标均有所改善,与IgAN组相比差异均有统计学意义(P均<0.05),部分指标与对照组相比差异无统计学意义(P>0.05)。结论 1,25(OH)2D抑制IgAN鼠Peyer小结Tfh和B细胞分化,抑制Gd-IgA1生成,对Peyer小结微环境起保护作用。Objective To explore the possible role of vitamin D in the pathogenesis of IgA nephropathy (IgAN). Me- thods After the IgAN model was successfully induced at 12 weeks, the BALB/C mice were randomly divided into IgAN group (n=15) and IgAN+VitD group (n=15). The nephrosis mice were administrated with 100 μl/d propylene glycol or propyl- ene glycol+1,25(OH)2D, 3 ng/(100g·d), for 6 weeks. The control group was setted (n=15). The level of 24 hour urine protein was determined at week 0, 12 and 18. At week 18, the levels of serum 25(OH)D, fibroblast growth factor 23 (FGF23) and galactose- deficient IgA1 (Gd-IgA1) were detected. The mRNA and protein expressions of intefleukin-21 (IL-21) in Peyer's patches (PPs) were detected by fluorescent quantitative reverse transcription-polymerase chain reaction and western blot respectively. The protein expression of Bcl-6 was detected by western blot. The percentages of Tfh cells/T lymphocytes, B220+IgM+/B lympho- cytes, B220+IgA+/B lymphocytes, B220-IgA+/B lymphocytes in PPs were determined by flow cytometry. Results Compared with control group, the levels of 24 hour urine protein, FGF23 and Gd-IgA1 were increased, serum 25(OH)D was decreased, the mRNA and protein expressions of IL-21 and the protein level of Bcl-6 were increased, the percentages of Tfh cells/T lym- phocytes, B220+IgM+/B lymphocytes, B220+IgA+/B lymphocytes, B220IgA+/B lymphocytes were elevated in IgAN group (P〈0.05). These indicators were improved in IgAN+VitD group. Compared with the IgAN group, the differences were statisti- cally significant (P〈0.05), however compared with control group, some indicators showed no significant differences (P〉0.05). Conclusions 1,25(OH)2D may protect the microenvironment of PPs in IgAN through inhibiting the differentiation of Tfh cellsand B cells and the generation of Gd-IgA1.
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