BACKGROUND The leptin receptor-deficient knockout (db/db) mouse is a well-established model for studying type II diabetes mellitus (T2DM). T2DM is an important risk factor of intervertebral disc degeneration (IVDD). Although the relationship between type I diabetes and IVDD has been reported by many studies, few studies have reported the effects of T2DM on IVDD in db/db mice model. METHODS Mice were separated into 3 groups: wild-type (WT), db/db, and IGF-1 groups (leptin receptor-deficient mice were treated with insulin-like growth factor-1 (IGF-1). To observe the effects of T2DM and glucose-lowering treatment on IVDD, IGF-1 injection was used. The IVD phenotype was detected by H&E and safranin O fast green staining among db/db, WT and IGF-1 mice. The levels of blood glucose and weight in mice were also recorded. The changes in the mass of the trabecular bone in the fifth lumbar vertebra were documented by micro-computed tomography (micro-CT). Tunnel assays were used to detect cell apoptosis in each group. RESULTS The weight of the mice were 27.68 ± 1.6 g in WT group, which was less than 57.56 ± 4.8 g in db/db group, and 52.17 ± 3.7 g in IGF-1 injected group (P < 0.05). The blood glucose levels were also significantly higher in the db/db mice group. T2DM caused by leptin receptor knockout showed an association with significantly decreased vertebral bone mass and increased IVDD when compared to WT mice. The db/db mice induced by leptin deletion showed a higher percentage of MMP3 expression as well as cell apoptosis in IVDD mice than WT mice (P < 0.05), while IGF-1 treatment reversed this situation (P < 0.05). CONCLUSIONS T2DM induced by leptin receptor knockout led to IVDD by increasing the levels of MMP3 and promoting cell apoptosis. IGF-1 treatment partially rescue the phenotype of IVDD induced by leptin receptor knockout.

中文翻译：

---

瘦素受体缺乏引起的II型糖尿病小鼠椎间盘退变。

背景技术瘦素受体缺陷型敲除（db / db）小鼠是研究II型糖尿病（T2DM）的公认模型。T2DM是椎间盘退变（IVDD）的重要危险因素。尽管许多研究都报告了I型糖尿病与IVDD之间的关系，但很少有研究报道db / db小鼠模型中T2DM对IVDD的影响。方法将小鼠分为野生型（WT），db / db和IGF-1组3组（瘦素受体缺陷型小鼠用胰岛素样生长因子-1（IGF-1）治疗），观察其作用。 T2DM和降糖治疗对IVDD的影响，采用IGF-1注射，通过H＆E和番红蛋白O快速绿色染色法检测db / db，WT和IGF-1小鼠的IVD表型。还记录了小鼠。微型计算机断层扫描（micro-CT）记录了第五个腰椎中小梁骨的质量变化。使用隧道测定法检测每组中的细胞凋亡。结果WT组小鼠体重为27.68±1.6 g，db / db组小鼠为57.56±4.8 g，IGF-1注射组小鼠为52.17±3.7 g（P <0.05）。db / db小鼠组的血糖水平也明显更高。与WT小鼠相比，瘦素受体敲除引起的T2DM与椎骨量明显减少和IVDD增加有关。瘦素缺失引起的db / db小鼠在IVDD小鼠中显示出比WT小鼠更高的MMP3表达百分比和细胞凋亡（P <0.05），而IGF-1处理逆转了这种情况（P <0.05）。结论瘦素受体敲除诱导的T2DM通过增加MMP3水平和促进细胞凋亡导致IVDD。IGF-1治疗可部分挽救瘦素受体敲除诱导的IVDD表型。