脂联素对2型糖尿病大鼠骨髓微环境氧化应激水平及骨吸收的影响  

Effects of adiponectin on oxidative stress and bone resorption in the bone marrow microenvironment of type 2 diabetic rats

作　　者：郭耀文 渠鹏霞 胡希鉴 赵倩[4] 朱亦堃[4] GUO Yao-wen;QU Peng-xia;HU Xi-jian;ZHAO Qian;ZHU Yi-kun(Department of Respiration and Critical Care Medicine,the Ninth Clinical Medicine College of Shanxi Medical University-Taiyuan Center Hospital,Taiyuan 030009,China;Department of Endocrinology,the Ninth Clinical Medicine College of Shanxi Medical University-Taiyuan Center Hospital,Taiyuan 030009,China;Department of Orthopedics,the Second Hospital of Shanxi Medical University,Taiyuan 030001,China;Department of Endocrinology,the Second Hospital of Shanxi Medical University,Taiyuan 030001,China)

机构地区：[1]山西医科大学第九临床医学院-太原市中心医院呼吸与危重症医学科,太原030009 [2]山西医科大学第九临床医学院-太原市中心医院内分泌科,太原030009 [3]山西医科大学第二医院骨科,太原030001 [4]山西医科大学第二医院内分泌科,太原030001

出　　处：《中华骨质疏松和骨矿盐疾病杂志》2019年第4期369-376,共8页Chinese Journal Of Osteoporosis And Bone Mineral Research

基　　金：山西省卫生和计划生育委员会科研项目(201601044)

摘　　要：目的 探讨脂联素(adiponectin,APN)对2型糖尿病大鼠骨髓微环境氧化应激水平及骨吸收指标的影响及其可能的作用机制。方法 将6周龄雄性SD大鼠60只随机分为正常对照组、糖尿病模型组。将建模成功大鼠36只随机分为糖尿病组(DM组)和APN干预组(APN组),APN组予腹腔注射球形APN 10 μg/(kg·d)。干预后分别于4、8、12周检测骨髓糖基化终末产物(advanced glycation end products,AGEs)、晚期氧化蛋白产物(advanced oxidation protein products,AOPP)、骨保护素(osteoprotegerin,OPG)、核因子κB受体活化素配体(receptor activator of nuclear fator-κB ligand,RANKL)、抗酒石酸酸性磷酸酶(tartrate-resistant acid phosphatase,TRAP)水平,骨组织HE染色观察骨小梁结构。结果 正常对照组大鼠骨组织AGEs、骨髓上清液AOPP水平随饲养时间延长无明显变化,TRAP水平逐渐升高,DM组及APN组上述指标水平逐渐升高,各组骨髓细胞中OPG /RANKL及骨密度(bone mineral density,BMD)均降低。组间比较,12周时,DM组AGEs(1 041.44±82.20)、AOPP(1 260.86±263.71)pg/mL及TRAP(65.12± 4.44)pg/mL 水平较正常组AGEs(276.48±54.97)、AOPP(279.69±54.57)pg/mL及TRAP(57.60±6.55)pg/mL水平明显升高( P <0.05),DM组OPG/RANKL(5.91±1.69)、BMD(0.19± 0.03)g/m 2 水平较正常组OPG/RANKL(29.62±9.78)、BMD(0.25±0.01)g/m 2水平显著降低( P <0.05);APN组AGEs(691.44±106.76)、AOPP(936.90±89.58)pg/mL及TRAP(55.63±2.73)pg/mL水平较DM组明显减低( P <0.05),OPG /RANKL(29.70±6.26)、BMD(0.24±0.01)g/m 2水平较DM组明显升高( P <0.05)。骨组织形态学观察可见4周时三组间骨小梁结构尚无明显差异;12周时DM组与对照组相比骨小梁稀疏变细,破坏严重,而APN组与DM组相比骨小梁结构有所改善。结论 2型糖尿病大鼠骨髓微环境中氧化应激程度加重,可能诱导破骨细胞生成增多而导致骨吸收增强,外源性APN可能通过降低骨髓微环境氧化应激水平,降低骨吸收,从而对骨代谢起正向调节�Objective To observe the effect of adiponectin (APN) on the expression of oxidative stress and bone resorption index in bone marrow microenvironment of type 2 diabetic rats, and to explore the possible mechanism. Methods Six-week old male SD rats were randomly divided into normal control group and diabetic model group. The 36 successfully-induced diabetic rats were divided into diabetic group (DM group) and APN intervention group (APN group). The rats in APN group were injected with APN 10 μg/(kg·d) by intraperitoneal injection. The rats were sacrificed at 4, 8, and 12 weeks after intervention to detect the expression of tartrate-resistant acid phosphatase(TRAP), receptor activator of nuclear fator-κB ligand(RANKL), osteoprotegerin(OPG), advanced oxidation protein products(AOPP) and advanced glycation end products(AGEs) in bone tissue. HE staining was used to observe the bone microstructure (trabecular bone density and cortical thickness). Results With the change of time, the expression of AGEs and AOPP in normal rats were not significantly different, and TRAP was increased in normal rats, but all the three indices were increased in DM group and APN intervention group ( P <0.05). In addition, the OPG/RANKL and BMD value in each group were gradually decreased. At 12 weeks, the expression level of AGEs (1 041.44±82.20), AOPP (1 260.86± 263.71)pg/mL, and TRAP (65.12± 4.44)pg/mL in the DM group were higher than the expression level of AGEs (276.48±54.97), AOPP (279.69±54.57)pg/mL, and TRAP (57.60±6.55)pg/mL in the control group ( P <0.05), and the OPG/RANKL (5.91±1.69) and BMD (0.19±0.03)g/m 2 values in the DM group were significantly lower than the OPG/RANKL (29.62±9.78) and BMD (0.25±0.01)g/m 2 values in the control group ( P <0.05). Compared with DM group, the expression level of AGEs (691.44±106.76), AOPP (936.90±89.58)pg/mL, TRAP (55.63±2.73) pg/mL, the OPG/RANKL (29.7±6.26) and BMD (0.24±0.01)g/m 2 values were improved after APN intervention ( P <0.05). At 4 weeks, the trabecular bone structur

关 键 词：糖尿病 骨质疏松症 氧化应激 脂联素 

分 类 号：R589[医药卫生—内分泌] R681[医药卫生—内科学]