活性维生素D通过下调TLR4介导的炎症反应通路对胰岛素抵抗大鼠肾脏的保护作用  

Active vitamin D protects the kidneys of insulin resistant rats by downregulating the TLR4-mediated inflammatory response pathway

作　　者：房方[1] 刘雅馨 张鑫[1] 朱梅[1] Fang Fang;Liu Yaxin;Zhang Xin;Zhu Mei(Department of Endocrinology and Metabolism,Tianjin Medical University General Hospital,Tianjin 300052,China)

机构地区：[1]天津医科大学总医院内分泌代谢科,天津300052

出　　处：《中华内分泌代谢杂志》2024年第8期690-696,共7页Chinese Journal of Endocrinology and Metabolism

基　　金：天津市教委科研计划项目(2021KJ208)。

摘　　要：目的探究活性维生素D对胰岛素抵抗(insulin resistance,IR)所致肾病的保护作用及其机制。方法选取雄性SD大鼠分成3组:正常对照组(C组),单纯高脂喂养组(HF组)和高脂喂养活性维生素D干预组(VD组)。比较各组间血清生化指标、肾脏组织细胞形态、Toll样受体(Toll-like receptor,TLR)4-髓分化因子(myeloid differentiation factor,MyD)88-NF-κB炎症反应通路在mRNA和蛋白表达水平上的差异。结果HF组大鼠存在明显IR,血清胱抑素C、丙氨酸转氨酶、天冬氨酸转氨酶、三酰甘油、低密度脂蛋白胆固醇和C反应蛋白水平均较C组显著升高;VD组大鼠上述各指标均较HF组明显改善。与C组大鼠相比,HF组大鼠肾小球及肾小管形态异常,肾间质大量炎症细胞浸润;VD组大鼠肾脏组织细胞形态较HF组大鼠明显改善。实时荧光定量PCR、免疫组织化学和蛋白质免疫印迹法结果提示HF组大鼠肾脏组织中TLR4、MyD88和NF-κB的mRNA和蛋白表达水平较C组显著增加;VD组上述指标的表达水平较HF组下降。结论本研究结果提示TLR4-MyD88-NF-κB炎症反应通路在IR肾病的发病机制中发挥重要作用,而补充活性维生素D可以通过下调TLR4介导的炎症反应通路保护IR大鼠的肾脏。希望今后有更多基础和临床研究聚焦IR肾病,从而为IR肾病的防治提供更多思路和证据。Objective To explore the protective effect and mechanism of active vitamin D against kidney disease induced by insulin resistance(IR)and its underlying mechanisms.Methods Male SD rats were divided into three groups:normal control group(group C),simple high-fat group(group HF),and high-fat with active vitamin D group(group VD).Differences of serum biochemical indicators,renal tissue cell morphology,Toll-like receptor(TLR)4-(myeloid differentiation factor,MyD)88-NF-κB inflammatory response pathway expression in mRNA and protein levels were compared among different groups.Results Rats in group HF showed significant IR,higher serum levels of cystatin C,alanine aminotransferase,aspartate aminotransferase,triglycerides,low density lipoprotein-cholesterol,and C-reactive protein compared to group C.Rats in group VD demonstrated significant improvements in these indicators compared with group HF.Compared with rats in group C,the morphology of renal glomeruli and tubules in group HF was abnormal,with a large number of inflammatory cells infiltrating the renal interstitium.The situation in group VD was significantly improved compared with group HF.The results of real-time fluorescence quantitative PCR,immunohistochemistry,and western blot showed higher TLR4,MyD88,and NF-κB levels in the renal tissues of group HF than those in group C.The levels of the above indicators in group VD were lower than those in group HF.Conclusion The results of this study suggest that TLR4-MyD88-NF-κB inflammatory response pathway play an important role in the pathogenesis of IR nephropathy,and supplementing with active vitamin D can protect the kidneys of IR rats by downregulating the TLR4-mediated inflammatory response pathway.Future basic and clinical research should focus on IR nephropathy to provide more insights and evidence for prevention and treatment.

关 键 词：胰岛素抵抗 肾病 维生素D TOLL样受体4 

分 类 号：R692[医药卫生—泌尿科学] R587.2[医药卫生—外科学]