Orexin-2受体激动剂不同给药方式对去卵巢糖尿病大鼠骨组织的影响  

Effects of orexin-2 receptor agonist on bone tissue of ovariectomized diabetic rats

作　　者：张丽媛 谭丹丹 纳青青 刘钰瑜 余永杰 周丽敏 ZHANG Li-yuan;TAN Dan-dan;NA Qing-qing;LIU Yu-yu;YU Yong-jie;ZHOU Li-min(Department of Anatomy,Guangdong Medical College,Zhanjiang 524023,Guangdong,China;Department of Pharmacy,Guangdong Medical College,Zhanjiang 524023,Guanagdong,China)

机构地区：[1]广东医科大学解剖教研室,广东湛江524023 [2]广东医科大学药理学教研室,广东湛江524023

出　　处：《中华骨质疏松和骨矿盐疾病杂志》2020年第6期539-546,共8页Chinese Journal Of Osteoporosis And Bone Mineral Research

基　　金：广东省医学科技技术研究基金(B2017014);湛江市财政基金科技专项竞争性分配项目(2015A01030)。

摘　　要：目的研究orexin-2受体激动剂对去卵巢糖尿病大鼠骨组织的影响。方法选取成年雌性SD大鼠作为动物模型,分为5组,每组6只。正常组:正常SD大鼠连续8周每天接受缓冲液注射;模型组:SD大鼠进行去卵巢手术,术后1周腹腔注射链脲佐菌素60 mg/kg,连续8周每天接受缓冲液注射;口服给药组、腹腔给药组和侧脑室给药组:大鼠给予orexin-2受体激动剂(Ala11,d-Leu15-orexin B),连续8周。实验8周后处死大鼠,用双能X线骨矿物质密度检测仪检测左侧股骨及第5腰椎骨密度;采用半自动图像分析系统,对左侧胫骨上段进行骨形态计量学参数的分析;分析股骨和第5腰椎的生物力学性能。结果与正常组相比,模型组股骨的各项生物力学性能指标呈明显下降趋势,其中弹性载荷值,最大载荷值、断裂载荷值,分别降低19.63%(P<0.01)、21.08%(P<0.01)和24.58%(P<0.01),胫骨上段的骨小梁数量减少,骨小梁分离度增加。每毫米破骨细胞数和破骨细胞贴壁长度增加,侧脑室给药组能改善成模组大鼠骨组织的上述指标,差异有统计学意义(P<0.05);但是口服给药组和腹腔注射给药组不能改善模型组骨丢失指标,差异无统计学意义(P>0.05)。结论侧脑室给予orxin-2受体激动剂能改善去卵巢糖尿病大鼠的骨微结构,防治骨质疏松症。Objective To study the effects of Orexin-2 receptor agonist on bone tissue of ovariectomized diabetic rats.Methods Adult female SD rats were selected as animal models and divided into 5 groups with 6 rats in each group.Normal group:Normal SD rats received buffer injection daily for 8 weeks.Model group:SD rats underwent ovariectomies,and received intraperitoneal injection of streptozotocin 60 mg/kg weekly after the operation,and received daily buffer injection for 8 weeks continuously.Oral,intraperitoneal,and lateral ventricle groups were given Orexin-2 receptor agonists(Ala11,D-LeU15-Orexin B)for 8 weeks.After 8 weeks,the rats were sacrificed,and the bone mineral density of the left femur and the fifth lumbar vertebra was measured by dual-energy X-ray absorptcometry.Semi-automatic image analysis system was used to analyze bone morphometric parameters in the upper left tibia segment.The biomechanical properties of femur and the fifth lumbar vertebra were analyzed.Results Compared with the normal group,the biomechanical performance index of femur in the model group showed a significant decrease trend,in which the elastic load value,maximum load value,and fracture load value were reduced to 19.63%(P<0.01),21.08%(P<0.01),and 24.58%(P<0.01),respectively.The number of trabecular bone in the upper tibia segment decreased,the degree of trabecular bone separation increased;the number of osteoclasts per millimeter and the length of osteoclasts adherent to the wall increased.The lateral ventricle administration group could improve the above indicators of bone tissue in the model group(P<0.05),but the oral administration group and the intraperitoneal injection group could not improve the indicators of bone loss in the model group(P>0.05).Conclusion Orxin-2 receptor agonist in lateral ventricle can improve the bone microstructure of ovariectomized diabetic rats and prevent osteoporosis.

关 键 词：orexin-2受体激动剂 骨质疏松 糖尿病 去卵巢大鼠 

分 类 号：R683[医药卫生—骨科学]