Jiang Bo, Mou Yan Jie, Zhang Xian Mei, Lu Kun, Xie Ping, Rao Yan Ling, Cong Ze Wei, Sun Qin Guo
Department of Traditional Chinese Medicine, Wuhan Third Hospital, Wuhan, 430060, China.
Comb Chem High Throughput Screen. 2024;27(5):786-796. doi: 10.2174/0113862073261310231113062630.
Diabetic osteoporosis (DOP) belongs to the group of diabetes-induced secondary osteoporosis and is the main cause of bone fragility and fractures in many patients with diabetes. The aim of this study was to determine whether Ziyin Bushen Fang (ZYBSF) can improve DOP by inhibiting autophagy and oxidative stress.
Type 1 diabetes mellitus (T1DM) was induced in rats using a high-fat high-sugar diet combined with streptozotocin. Micro-CT scanning was used to quantitatively observe changes in the bone microstructure in each group. Changes in the serum metabolites of DOP rats were analyzed using UHPLC-QTOF-MS. The DOP mouse embryonic osteoblast precursor cell model (MC3T3-E1) was induced using high glucose levels.
After ZYBSF treatment, bone microstructure significantly improved. The bone mineral density, trabecular number, and trabecular thickness in the ZYBSF-M and ZYBSF-H groups significantly increased. After ZYBSF treatment, the femur structure of the rats was relatively intact, collagen fibers were significantly increased, and osteoporosis was significantly improved. A total of 1239 metabolites were upregulated and 1527 were downregulated in the serum of T1DM and ZYBSF-treated rats. A total of 20 metabolic pathways were identified. In cellular experiments, ZYBSF reduced ROS levels and inhibited the protein expression of LC3II / I, Beclin-1, and p-ERK.
ZYBSF may improve DOP by inhibiting the ROS/ERK-induced autophagy signaling pathway.
糖尿病性骨质疏松症(DOP)属于糖尿病诱发的继发性骨质疏松症,是许多糖尿病患者骨脆性和骨折的主要原因。本研究旨在确定滋阴补肾方(ZYBSF)是否能通过抑制自噬和氧化应激来改善DOP。
采用高脂高糖饮食联合链脲佐菌素诱导大鼠1型糖尿病(T1DM)。使用微型计算机断层扫描(Micro-CT)定量观察各组骨微结构的变化。采用超高效液相色谱-四极杆飞行时间质谱(UHPLC-QTOF-MS)分析DOP大鼠血清代谢物的变化。使用高糖水平诱导DOP小鼠胚胎成骨细胞前体细胞模型(MC3T3-E1)。
ZYBSF治疗后,骨微结构显著改善。ZYBSF-M组和ZYBSF-H组的骨密度、骨小梁数量和骨小梁厚度显著增加。ZYBSF治疗后,大鼠股骨结构相对完整,胶原纤维显著增加,骨质疏松明显改善。T1DM大鼠和ZYBSF治疗大鼠血清中共有1239种代谢物上调,1527种代谢物下调。共鉴定出20条代谢途径。在细胞实验中,ZYBSF降低了活性氧(ROS)水平,抑制了微管相关蛋白1轻链3II/I(LC3II/I)、自噬相关蛋白1(Beclin-1)和磷酸化细胞外信号调节激酶(p-ERK)的蛋白表达。
ZYBSF可能通过抑制ROS/ERK诱导的自噬信号通路来改善DOP。