Yu Jiali, Da Jingjing, Dong Rong, Sun Yi, Nie Yingjie, Yu Fuxun, Zuo Li, Zha Yan
Department of Nephrology, Guizhou Provincial People's Hospital, Guiyang, Guizhou Province, China.
Department of Immunology, Guizhou Medical University, Guiyang, Guizhou Province, China.
Endocr Metab Immune Disord Drug Targets. 2018;18(3):241-250. doi: 10.2174/1871530318666180131102707.
This study was established to investigate the contribution of high mobility group nucleosome-binding protein 1 (HMGN1)/ Toll-like receptor 4 (TLR4) pathway in diabetic nephropathy (DN). And as an intervention of the potential mechanism above, the insulin growth factor 1 receptor (IGF-1R) inhibitor was examined for its therapeutic effect in the diabetic mice.
Male C57BL/6J mice were administered streptozotocin(STZ) to induce diabetes and thus divided into 5 groups: the untreated group (DN group), the benazepril-treated group (BEN-DN group), the insulin-treated group (INS-DN group) and the IGF-1R inhibitor-treated group (IGF-DN group). Immunohistochemistry and in situ hybrization were performed to detect the expression of HMGN1 and TLR4 in renal tissue. To evaluate the effect of IGF-1R inhibitor, levels of blood glucose and kidney/ body weight (KW/BW) were measured. And morphological changes and mesangial matrix expansion in kidneys were also detected.
Increased expression of HMGN1 and TLR4 in renal tissue of STZ-induced type1 diabetic mellitus (T1DM) mice models was observed. IGF-1R inhibitor attenuate the established nephropathy with reduced expression of TLR4 protein, as revealed by a decrease in mesangial index.
IGF-1R inhibitor might have therapeutic potential in DN through inhibition of HMGN1/TLR4 pathway.
本研究旨在探讨高迁移率族核小体结合蛋白1（HMGN1）/Toll样受体4（TLR4）通路在糖尿病肾病（DN）中的作用。作为对上述潜在机制的干预措施，研究胰岛素生长因子1受体（IGF-1R）抑制剂对糖尿病小鼠的治疗效果。
给雄性C57BL/6J小鼠注射链脲佐菌素（STZ）诱导糖尿病，将其分为5组：未治疗组（DN组）、苯那普利治疗组（BEN-DN组）、胰岛素治疗组（INS-DN组）和IGF-1R抑制剂治疗组（IGF-DN组）。采用免疫组织化学和原位杂交技术检测肾组织中HMGN1和TLR4的表达。为评估IGF-1R抑制剂的效果，检测血糖水平和肾重/体重（KW/BW）。同时检测肾脏的形态学变化和系膜基质扩张情况。
在链脲佐菌素诱导的1型糖尿病（T1DM）小鼠模型的肾组织中，观察到HMGN1和TLR4表达增加。IGF-1R抑制剂可减轻已形成的肾病，系膜指数降低表明TLR4蛋白表达减少。
IGF-1R抑制剂可能通过抑制HMGN1/TLR4通路对糖尿病肾病具有治疗潜力。
