GLP-1对2型糖尿病大鼠血清OPG、RANKL及骨密度的影响研究

The effect of GLP-1 on serum concentrations of OPG and RANKL and bone mineral density in type 2 diabetic rats

目的探讨GLP-1类似物利拉鲁肽对糖尿病大鼠血清OPG、RANKL及骨密度的影响。方法健康雄性SD大鼠随机分为正常对照组(NC组)、糖尿病组(DM)、利拉鲁肽低剂量组(LR-L)、利拉鲁肽高剂量组(LR-H)。高脂高糖饮食联合小剂量链脲佐菌素(STZ)诱导建立2型糖尿病大鼠模型,低剂量组予利拉鲁肽400μg/(kg.d)皮下注射,高剂量组予利拉鲁肽800μg/(kg.d)皮下注射,给药4w后处死大鼠,测血糖、血钙、血磷、碱性磷酸酶、胆固醇、甘油三酯,ELISA法检测OPG、RANK,DXA法检测大鼠骨密度。结果与NC组比较,1 DM组、LR-L组、LR-H组体重均减轻,LR-L组、LR-H组较DM组更轻,但LR-L组与LR-H组间比较无差异;2DM组、LR-L组、LR-H组血糖均升高,LR-L组、LR-H组血糖较DM组低,但LR-L组与LR-H组间比较无差异;3DM、LR-H、LR-L组血清OPG、RANKL明显升高,差异具有统计学意义(P<0.05),LR-L组OPG较DM组更高差异有统计学意义(P<0.05),LR-H组OPG高于DM组但差异无统计学意义;LR-H与LR-L组RANKL明显低于DM组;4DM组血清OPG/RANKL比值低于NC组,LR-L、LR-H组血清OPG/RANKL较DM升高,差异具有统计学意义(P<0.05);5DM组、LR-L、LR-H组大鼠全身及各部位骨密度均降低,差异具有统计学意义(P<0.05),但DM组、LR-L组、LR-H组3组间差异无统计学意义。结论利拉鲁肽具有降低2型糖尿病大鼠体重、减低血清RANKL、升高血清OPG的作用,但利拉鲁肽治疗后未见骨密度的提高。

Objective To investigate the effect of GLP-1 analogue liraglutide on the serum levels of osteoprotegerin（ OPG）,receptor activator of nuclear factor-kappa B ligand（ RANKL）,and bone mineral density in diabetic rats. Methods Healthy male SD rats were randomly divided into normal control group（ NC）,diabetes mellitus（ DM） group,lowdose liraglutide group（ LRL）,and high dose liraglutide group（ LR-H）. Type 2 diabetic rat model was induced with high fat and sugar diet combined with low-dose streptozotocin（ STZ）. Rats in LR-L group received 400 ug / kg / d of liraglutide with subcutaneous injection. Rats in LR-H group received 800 ug / kg / d of liraglutide subcutaneously. After 4 weeks,rats were sacrificed. The concentrations of blood glucose,serum calcium,phosphorus,alkaline phosphatase,total cholesterol,and triglyceride were measured. OPG and RANK were detected using ELISA method. Bone mineral density was detected with DEXA. Results Comparing with those in NC group,1） The body weight reduced in DM,LR-L,and LR-H group. The body weight in LR-L and LR-H group was lighter than that in the DMgroup.It was not different between LR-L group and LR-H group. 2） Blood glucose increased in DM,LR-L,and LR-H group. Blood glucose in LR-L and LR-H group was lower than that in DMgroup. It was not different between LR-L and LR-H group. 3） The serum concentrations of OPG and RANKL increased significantly in DM,LR-H,and LR-L group,and the difference was statistically significant（ P〈 0. 05）. The serum concentration of OPG in LR-L group is higher than that in DMgroup,and the difference was statistically significant（ P 〈0. 05）. The serum concentration of OPG in LR-H group was higher than that in DMgroup,but the difference was not statistically significant. The serum concentration of RANK in LR-H and LR-L group was significantly lower than that in DMgroup. 4） The serum OPG / RANKL ratio in DMgroup was lower than that in NC group. It was higher in LR-L and LR-H group than that in DMgroup,and the difference was statistically significant（ P〈 0. 05）. 5） The whole body BMD was lower in DM,LR-I,and LR-H group,and the difference was statistically significant（ P 〈0. 05）. There was no significant difference among the 3 groups. Conclusion Liraglutide plays a role in reducing the body weight in type 2 diabetic rats,reducing the serum RANKL, and elevating serum OPG. However, bone mineral density does not increase after liraglutide treatment.