伊班膦酸钠激活Nrf2/HO-1信号通路减轻糖尿病性骨质疏松大鼠炎症损伤的研究  

Ibandronate alleviates inflammatory damage in diabetic osteoporosis rats by activating Nrf2/HO-1 signaling pathway

作　　者：刘晓莉[1] 朱沁芳[1] 李金娟[1] 杨历新[1] LIU Xiao-li;ZHU Qin-fang;LI Jin-juan;YANG Li-xin(Department of Endocrinology,Qinghai Provincial People’s Hospital,Xining 810000,Qinghai Province,China)

机构地区：[1]青海省人民医院内分泌科,青海西宁810000

出　　处：《中国临床药理学杂志》2024年第2期230-233,共4页The Chinese Journal of Clinical Pharmacology

基　　金：青海省科技计划基金资助项目(2020-ZJ-930)。

摘　　要：目的探讨伊班膦酸钠(IB)通过激活核转录因子红系2相关因子2(Nrf2)/血红素加氧酶1(HO-1)信号通路减轻糖尿病性骨质疏松大鼠炎症损伤的机制。方法用小剂量链脲佐菌素多次腹腔注射方式构建糖尿病大鼠模型,再行双侧卵巢切除术诱导骨质疏松,建立糖尿病合并骨质疏松(T2DOP)大鼠模型。将T2DOP模型大鼠分为模型组、对照组、联合组和低、中、高剂量实验组,每组8只;另取8只糖尿病模型大鼠作为空白组。模型组给予0.9%NaCl;对照组给予等体积的二甲基亚砜;低、中、高剂量实验组分别给予2、10、50 mg·kg^(-1)IB;联合组给予50 mg·kg^(-1)IB+50 mg·kg^(-1)ML385。7组大鼠每天腹腔注射1次,给药12周。用钙黄蛋白双标记法检测骨组织形态学参数,用蛋白质印迹法检测Nrf2和HO-1蛋白的表达水平。结果中、高剂量实验组和联合组、对照组、模型组和空白组的骨组织形态学参数分别为1.74±0.32、2.94±0.58、0.98±0.32、1.01±0.24、0.98±0.42和2.92±0.42,Nrf2蛋白相对表达水平分别为0.99±0.09、1.47±0.12、0.51±0.06、0.52±0.06、0.52±0.05和1.48±0.12,HO-1蛋白相对表达水平分别为1.02±0.11、1.33±0.14、0.61±0.05、0.59±0.06、0.62±0.06和1.29±0.13。对照组的上述指标与中、高剂量实验组比较,在统计学上差异均有统计学意义(均P<0.05)。结论IB通过激活Nrf2/HO-1信号通路,减轻糖尿病性骨质疏松大鼠的炎症损伤并修复骨微观结构。Objective To investigate the potential mechanism of ibandronate sodium(IB)in alleviating inflammatory damage in diabetic osteoporosis rats by activating the nuclear transcription factor erythro 2-associated factor 2(Nrf2)/heme oxygenase-1(HO-1)signaling pathway.Methods Intraperitoneal injection of streptozotocin at several low doess was used to induce rat model of diabetes mellitus,then bilateral oophorectomy were used to establish type 2 diabetic osteoporosis(T2DOP)rat model.T2DOP model rats were divided into model group,control group,combined group and experimental-L,-M,-H groups,with 8 rats in each group;another 8 diabetic rats were selected as blank group.Model group was treated with normal saline.Control group was given the same volume of solvent.Experimental-L,-M,-H groups were given 2,10 and 50 mg·kg^(-1)IB.Combined group was treated with 50 m g·kg^(-1)IB and 50 mg·kg^(-1)ML385.Seven groups were administered intraperitoneally once a day for 12 weeks.After 12 weeks of treatment,the bone morphologic parameters were detected by calxanthoprotein double labeling method,the expression levels of Nrf2 and HO-1 pathway protein were detected by Western blot.Results The bone morphologic parameters of experimental-M,-H groups,combined group,control group,model group and blank group were 1.74±0.32,2.94±0.58,0.98±0.32,1.01±0.24,0.98±0.42 and 2.92±0.42;the relative expression levels of Nrf2 protein were 0.99±0.09,1.47±0.12,0.51±0.06,0.52±0.06,0.52±0.05 and 1.48±0.12;the relative expression levels of HO-1 protein were 1.02±0.11,1.33±0.14,0.61±0.05,0.59±0.06,0.62±0.06 and 1.29±0.13,respectively.The above indexes in the control group were statistically different with those in the experimental-M,-H groups(all P<0.05).Conclusion IB repairs bone microstructure and alleviates inflammation in diabetic osteoporosis rats by activating the Nrf2/HO-1 signaling pathway.

关 键 词：伊班膦酸钠 骨质疏松 核转录因子红系2相关因子2 血红素加氧酶1 

分 类 号：R97[医药卫生—药品]