二甲双胍抑制高迁移率族蛋白B1及晚期糖基化终末产物受体改善2型糖尿病大鼠种植体骨结合的研究  

Metformin improves implant osseointegration in type 2 diabetic rats through inhibition high mobility group box 1 and receptor for advanced glycation end product

作　　者：王惠[1] 李风兰[1] 张静怡 李毅 Wang Hui;Li Fenglan;Zhang Jingyi;Li Yi(Department of Prosthodontics,the Fifth Clinical Medical College of Shanxi Medical University,Taiyuan 030000,China;Department of Prosthodontics,Shanxi Medical University School and Hospital of Stomatology,Taiyuan 030000,China)

机构地区：[1]山西医科大学第五临床医学院口腔修复科,太原030000 [2]山西医科大学口腔医学院口腔医院修复科,太原030000

出　　处：《中华内分泌代谢杂志》2022年第9期789-797,共9页Chinese Journal of Endocrinology and Metabolism

基　　金：山西省应用基础研究计划(201901D111442);山西省重点研发计划(指南)项目(201703D321027-2)。

摘　　要：目的探讨二甲双胍对高迁移率族蛋白B1(high mobility group box 1,HMGB1)、晚期糖基化终末产物受体(receptor for advanced glycation end product,RAGE)在2型糖尿病大鼠种植体周表达的变化及影响骨结合的可能机制;探讨二甲双胍对非糖尿病大鼠骨结合的影响。方法40只6~8周雄性SD大鼠以随机数字表法随机分成4组,各10只:正常组(T0组)、正常+二甲双胍组(T1组)、糖尿病组(T2组)、糖尿病+二甲双胍组(T3组)。T2、T3组2型糖尿病模型造模成功后,所有大鼠双侧胫骨干骺端植入纯钛植体,当日T1、T3组以300 mg·kg^(-1)·d^(-1)二甲双胍灌胃,其余组以等量生理盐水灌胃。术后第4、8周每组随机处死5只大鼠,HE染色及微计算机断层扫描(micro-CT)观察骨结构;免疫组化及酶联免疫吸附测定检测相关因子表达。结果术后第4、8周,T3组种植体周骨小梁结构、新骨形成质量、骨微参数均优于T2组,且与T2组相比,T3组HMGB1、RAGE表达降低,骨钙素含量升高,肿瘤坏死因子-α表达降低(均P<0.01)。术后4周,T1组骨体积分数和骨小梁数目高于T0组[(0.569±0.013)%对(0.523±0.030)%,P=0.014;(1.695±0.059)/mm对(1.569±0.050)/mm,P=0.007]。术后8周,T1组骨小梁数目高于T0组[(2.324±0.337)/mm对(1.882±0.057)/mm,P=0.042],T1组RAGE含量显著低于T0组[(35.49±2.77)ng/L对(44.92±7.99)ng/L,P=0.005],T1组骨钙素含量显著高于T0组[(1.32±0.19)ng/L对(0.89±0.26)ng/L,P=0.001]。结论二甲双胍降低2型糖尿病大鼠种植体周HMGB1及配体RAGE表达,可能是促进种植体骨结合的机制之一;二甲双胍对非糖尿病大鼠具有骨保护作用。Objective To investigate the effects of metformin on the expression of high mobility group box 1(HMGB1)and receptor for advanced glycation end product(RAGE)around implants in type 2 diabetic rats and underlying mechanism on bone bonding.To investigate the effect of metformin on osseointegration in non-diabetic rats.Methods Forty male SD rats aged 6 to 8 weeks were randomly divided into 4 groups by random number table with 10 rats each:normal group(T0 group),normal+metformin group(T1 group),diabetic group(T2 group),and diabetic+metformin group(T3 group).After type 2 diabetes model was established in T2 and T3 groups,pure titanium implants were implanted in bilateral tibial epiphyseal of all rats.On the same day,T1 and T3 groups were given 300 mg·kg^(-1)·d^(-1)metformin,and other groups were gavaged with the same amount of normal saline.At the 4th and 8th week after surgery,5 rats in each group were randomly sacrificed,and bone structure was examined using HE staining and micro-computed tomography(micro-CT).The expression of related factors was detected with immunohistochemistry and enzyme linked immunosorbent assay.Results At the 4th and 8th week after surgery,the trabecular bone structure,new bone formation quality,and bone microparameters in T3 group were better than those in T2 group.Compared with T2 group,the expression of HMGB1 and RAGE was decreased,the content of osteocalcin was increased,and the expression of tumor necrosis factor-αwas decreased(all P<0.01).4 weeks after operation,bone volume/tissue volume and trabecular number in T1 group was higher than that in T0 group[(0.569±0.013)%vs(0.523±0.030)%,P=0.014;(1.695±0.059)/mm vs(1.569±0.050)/mm,P=0.007].8 weeks after operation,trabecular number in T1 group was higher than that in T0 group[(2.324±0.337)/mm vs(1.882±0.057)/mm,P=0.042].Compared with T0 group,the content of RAGE in T1 group was significantly decreased[(35.49±2.77)ng/L vs(44.92±7.99)ng/L,P=0.005].The osteocalcin content in T1 group was significantly higher than that in T0 group[(1.3

关 键 词：糖尿病 2型 二甲双胍 骨结合 高迁移率族蛋白B1 晚期糖基化终末产物受体 

分 类 号：R587.1[医药卫生—内分泌] R783[医药卫生—内科学]