CXCL16缺失缓解STZ诱导的糖尿病小鼠的肾脏病变

 目的: 探索CXCL16基因缺失对链脲佐菌素(STZ)引发的糖尿病小鼠肾脏病变的影响。方法: 选取8周龄雄性C57BL/6J CXCL16基因缺失(C16 KO)小鼠,以及相同年龄及背景的野生型(WT)小鼠,采用STZ诱导的方式,建立糖尿病小鼠模型,观察CXCL16基因缺失对糖尿病肾病发生发展的影响。结果: 在糖尿病病变方面,与STZ处理的WT小鼠相比,STZ诱导C16 KO糖尿病小鼠的空腹血糖显著降低,并且其葡萄糖耐受能力得到显著改善。在糖尿病引发的肾脏病变方面,STZ处理后,C16 KO糖尿病小鼠的尿蛋白量显著低于WT糖尿病小鼠,此外,C16 KO糖尿病小鼠的肾小球损伤也明显低于WT糖尿病小鼠。与此同时,与WT糖尿病小鼠相比,C16 KO糖尿病小鼠肾脏组织活性氧簇(ROS)、丙二醛(MDA)、氧化低密度脂蛋白(ox-LDL)水平及凝集素样氧化低密度脂蛋白受体 1(Lox-1)的mRNA表达水平均显著下调。此外,在STZ处理后,C16 KO糖尿病小鼠肾组织中的巨噬细胞移动抑制因子(MIF)、炎症因子TNF-α 和IL-6以及黏附因子ICAM-1和CXCL1的mRNA表达水平均显著低于WT糖尿病小鼠。结论: CXCL16基因缺失能显著抑制STZ诱导的糖尿病小鼠肾脏病变。

CXCL16 deficiency attenuates STZ-induced diabetic nephropathy in mice

AIM: To explore the effect of CXCL16 deficiency on streptozocin (STZ)-induced diabetic nephropathy in mice. METHODS: CXCL16 knockout (C16 KO) mice (8 years old) were used to build up diabetes model by treating with STZ.Age- and gender-matched wild-type (WT) C57BL/6J mice treated with STZ were used as control. All mice were fed with chow diets for 12 weeks, and the development of diabetic nephropathy was evaluated. RESULTS: Compared with the WT mice treated with STZ, C16 KO mice treated with STZ presented lower fasting glucose levels and better glucose tolerance power. C16 KO mice treated with STZ also had lower urine protein levels and smaller areas of glomerular injury as compared with WT mice treated with STZ. Furthermore, CXCL16 deficiency decreased the contents of renal reactive oxygen species (ROS), malondialdehyde (MDA) and oxidized low-density lipoprotein (ox-LDL) and the mRNA expression of lectin-like oxidized low-density lipoprotein receptor 1 (Lox-1), and attenuated the expression of renal inflammatory factors including tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6), as well as chemokines including intercellular cell adhesion molecular 1 (ICAM-1) and chemokine C-X-C motif ligand 1 (CXCL1). CONCLUSION: CXCL16 deficiency obviously inhibits the development of STZ-induced diabetic nephropathy in mice.