目的探讨Peyer小结在IgA肾病(IgAN)发病中的作用。方法雄性BALB/C小鼠予牛血清清蛋白、葡萄球菌肠毒素B诱导IgAN模型,另选40只正常雄性BALB/C小鼠作为对照组。第12周免疫荧光检测其肾组织IgA沉积,测定其血清总蛋白(TP)、清蛋白(Alb)、BUN、Cr、半胱氨酸蛋白酶抑制剂C(Cys C)。荧光定量反转录(RT)-PCR检测Peyer小结IL-21、转化生长因子-β1(TGF-β1)mRNA的表达。Western blot测定Peyer小结IL-21、B细胞淋巴瘤因子-6(Bcl-6)、B淋巴细胞诱导成熟蛋白-1(Blimp-1)蛋白表达。结果 1.IgAN组和对照组第0周、第6周、第12周24 h尿蛋白定量分别为(0.61±0.26)mg vs(0.67±0.22)mg、(3.61±0.75)mg vs(0.77±0.27)mg、(4.15±0.82)mg vs(2.09±0.51)mg,IgAN组第6周、第12周24 h尿蛋白均高于对照组(Pa<0.01)。2.IgAN组和对照组IL-21、TGF-β1 mRNA表达相对值分别为1.67±0.13 vs 1.48±0.13、1.21±0.09 vs 1.10±0.10,与对照组相比,IgAN组IL-21、TGF-β1 mRNA表达均增加,差异均有统计学意义(Pa<0.05)。3.Western blot显示IgAN组和对照组IL-21、Bcl-6、Blimp-1蛋白表达相对值分别为0.67±0.21 vs 0.45±0.10、0.34±0.21 vs 0.60±0.19、1.03±0.07 vs 0.67±0.07,与对照组相比,IgAN组IL-21、Blimp-1蛋白表达均显著增高,差异均有统计学意义(Pa<0.05),Bcl-6蛋白表达降低,差异有统计学意义(P<0.05)。结论 Peyer小结有促进B淋巴细胞向分泌IgA浆母细胞分化的微环境,参与IgAN的发病。
The aim of this study was to investigate the possible beneficial effects of Fenofibrate on renal ischemia-reperfusion injury（IRI） in mice and its potential mechanism. IRI was induced by bilateral renal ischemia for 60 min followed by reperfusion for 24 h. Eighteen male C57BL/6 mice were randomly divided into three groups： sham-operated group（sham）, IRI＋saline group（IRI group）, IRI＋Fenofibrate（FEN） group. Normal saline or Fenofibrate（3 mg/kg） was intravenously injected 60 min before renal ischemia in IRI group and FEN group, respectively. Blood samples and renal tissues were collected at the end of reperfusion. The renal function, histopathologic changes, and the expression levels of pro-inflammatory cytokines [interleukin-8（IL-8）, tumor necrosis factor alpha（TNF-α） and IL-6] in serum and renal tissue homogenate were assessed. Moreover, the effects of Fenofibrate on activating phosphoinositide 3 kinase/protein kinase B（PI3K/Akt） signaling and peroxisome proliferator-activated receptor-α（PPAR-α） were also measured in renal IRI. The results showed that plasma levels of blood urea nitrogen and creatinine, histopathologic scores and the expression levels of TNF-α, IL-8 and IL-6 were significantly lower in FEN group than in IRI group. Moreover, Fenofibrate pretreatment could further induce PI3K/Akt signal pathway and PPAR-α activation following renal IRI. These findings indicated PPAR-α activation by Fenofibrate exerts protective effects on renal IRI in mice by suppressing inflammation via PI3K/Akt activation. Thus, Fenofibrate could be a novel therapeutic alternative in renal IRI.
