利拉鲁肽通过自噬及改善氧化应激缓解大鼠糖皮质激素性骨质疏松

Liraglutide relieves glucocorticoid osteoporosis in rats through autophagy and improvement of oxidative stress

目的探讨利拉鲁肽对大鼠糖皮质激素性骨质疏松的作用及其可能机制。方法将30只健康8周龄雄性SD大鼠,随机分为正常对照组、地塞米松组以及地塞米松+利拉鲁肽干预组,干预12周后通过Micro-CT检测骨密度及骨微结构,试剂盒检测骨组织内活性氧(ROS)、超氧化物歧化酶(SOD)及丙二醛(MDA)含量,Western blot检测自噬特异性蛋白Beclin-1、Atg5、p62/SQSTM1W及Map1-LC3-Ⅱ的表达水平。结果地塞米松组股骨远端干骺端的骨密度(BMD)、骨小梁体积比率(BV/TV)、骨小梁数量(Tb.N)、骨小梁厚度(Tb.Th)、骨小梁间距(Tb.Sp)及骨小梁连接密度(Conn.D)均较正常对照组降低,骨组织内氧化应激产物ROS及MDA含量升高,抗氧化酶SOD活性降低,自噬相关蛋白Beclin-1、Atg5及Map1-LC3-Ⅱ表达水平均升高,p62/SQSTM1W蛋白表达水平下降(均P<0.05)。利拉鲁肽干预组大鼠的骨密度、骨微结构得到改善,骨组织内ROS及MDA含量降低,抗氧化酶SOD活性升高,自噬相关蛋白Beclin-1、Atg5及Map1-LC3-Ⅱ的表达水平下降,p62/SQSTM1W蛋白表达水平上升(均P<0.05)。结论利拉鲁肽能改善糖皮质激素造成的骨质疏松,其机制可能与调整自噬及改善氧化应激有关。

Objective To investigate the effects of liraglutide on glucocorticoid-induce osteoporosis rats and the possible mechanism.Methods Thirty healthy 8-week-old male SD rats were randomly divided into normal control group,dexamethasone group,and dexamethasone+liraglutide intervention group.After 12 weeks of intervention,BMD and bone microstructure were measured by Micro-CT.The kits were used to detect the content of reactive oxygen species(ROS),superoxide dismutase(SOD)and malondialdehyde(MDA)in bone tissue,Western blot was used to detect autophagy specific protein Beclin-1,Atg5,p62/SQSTM1 W and Map1-LC3-Ⅱexpression level.Results In the dexamethasone group,the bone density(BMD),trabecular bone volume ratio(BV/TV),trabecular bone volume(Tb.N),trabecular bone thickness(Tb.Th),and bone size of the distal femur Beam spacing(Tb.Sp)and trabecular bone connection density(Conn.D)were lower than those in the control group.The content of oxidative stress products ROS and MDA in bone tissue increased,the antioxidant enzyme SOD activity was reduced,and the expression levels of autophagy related proteins Beclin-1,Atg5 and Map1-LC3-Ⅱincreased,and the expression level of p62/SQSTM1 W protein decreased(all P<0.05).Bone density and bone microstructure of rats in the liraglutide intervention group were improved,ROS and MDA content in bone tissue reduced,antioxidant enzyme SOD activity was increased,and the expression levels of autophagy-related proteins Beclin-1,Atg5,and Map1-LC3-Ⅱdecreased,and the expression level of p62/SQSTM1 W protein increased(all P<0.05).Conclution Liraglutide can improve osteoporosis caused by glucocorticoids,and its mechanism may be related to adjusting autophagy and improving oxidative stress.