白藜芦醇对1型糖尿病小鼠骨组织代谢的影响
Effect of resveratrol on bone metabolism in type 1 diabetic mice
  
DOI:10.3969/j.issn.1006-7108.2020.01.003
中文关键词:  1型糖尿病  白藜芦醇  骨破坏  骨形成  动物实验
英文关键词:type 1 diabetes  resveratrol  bone destruction  bone formation  animal experimentation
基金项目:国家自然科学基金(81571625)
作者单位
刘方超 陈颖 董冰子 付正菊* 王颜刚 胡建霞 青岛大学附属医院内分泌科山东 青岛 266000 
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中文摘要:
      目的 探讨白藜芦醇(resveratrol,RESV)对初发1型糖尿病骨损害的影响,为临床上治疗1型糖尿病继发骨损害提供有价值的思路和启示。方法 将NOD小鼠分为正常(N)组、糖尿病(DM)组、胰岛素(INS)组、白藜芦醇(RESV)组。N组、DM组用生理盐水灌胃,INS组用0.2~0.4 U/(kg·d)甘精胰岛素注射液进行皮下注射,RESV组用200 mg/(kg·d)白藜芦醇进行灌胃治疗,治疗8周后取右侧股骨应用Micro-CT进行微观结构观察,并用左侧股骨进行碱性磷酸酶染色。同时检测骨组织相关基因OCN、Runx2、PPARr、TRAP的表达水平。结果 (1)Micro-CT结果显示,与正常组相比,糖尿病组骨密度降低(P=0.015),骨体积百分比降低(P=0.049);与糖尿病组相比,白藜芦醇治疗组骨密度升高(P=0.008),骨体积百分比升高(P=0.014)、骨表面密度增加(P=0.016),结构模型指数升高(P=0.029);与胰岛素治疗组相比,白藜芦醇治疗组骨小梁数目明显增加(P=0.018)。(2)骨组织切片碱性磷酸酶染色显示,糖尿病骨小梁变细、减少,成骨细胞数目明显减少;与糖病组相比,胰岛素组及白藜芦醇组成骨细胞明显增多。(3)实时荧光定量PCR结果显示,与正常组相比,糖尿病组TRAP、PPARr表达量增加;与糖尿病组相比,胰岛素治疗组和白藜芦醇治疗组TRAP、PPARr表达量降低,Runx2表达量增加。结论 白藜芦醇通过减少骨吸收并促进骨形成改善1型糖尿病鼠的骨质破坏。
英文摘要:
      Objective To investigate the effect of resveratrol (RESV) on bone damage in first-onset diabetes mellitus type 1, and to provide valuable ideas and inspiration for clinical treatment of bone damage secondary to diabetes mellitus type 1. Methods NOD mice were divided into normal (N) group, diabetes (DM) group, insulin-treated (INS) group, and resveratrol-treated (RESV) group. Mice in the N group and the DM group were intragastrically administered with 0.9% sodium chloride solution. Mice in the INS group was injected subcutaneously with 0.2-0.4 U/kg·d insulin injection. Mice in the RESV group was treated with 200 mg/kg·d of RESV. RESV was administered by intragastric administration. After 8 weeks of treatment, the right femur was collected for microstructural observation using Micro-CT. Alkaline phosphatase (ALP) staining was performed at the left femur. At the same time, the expression levels of bone tissue related genes, OCN, Runx2, PPARr, and TRAP were detected. Results (1) Micro-CT results showed that bone mineral density (BMD) decreased (P=0.015) and bone volume percentage (BV/TV) decreased in the diabetes group compared with those in the normal group (P=0.049). Compared with the diabetes group, the RESV-treated group had increased BMD (P=0.008), increased BV/TV (P=0.014), increased bone surface density (BS/TV) (P=0.016), and increased structural model index (SMI) (P=0.029). The number of trabecular bone (Tb.N.) was significantly increased in the resveratrol-treated group compared with in the insulin-treated group (P=0.018). (2) ALP staining of bone tissue sections showed that the trabecular bone was thinned, the number was reduced, and the number of osteoblasts were significantly reduced in DM group. Compared with the DM group, the number of osteoblasts were increased significantly in INS and RESV groups. (3) Real-time quantitative PCR (RT-PCR) results showed that compared with the normal group, the expression of TRAP and PPARr increased in the DM group. Compared with the DM group, the expression levels of TRAP and PPARr decreased in the INS group and the RESV group, but the expression of Runx2 was increased. Conclusion RESV improves bone destruction in type 1diabetes mellitus mice by reducing bone resorption and promoting bone formation.
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