2型糖尿病大鼠骨代谢特点及GLP-1类似物对骨代谢的影响

发布时间：2018-04-28 03:47

本文选题：2型糖尿病 + 大鼠　；参考：《昆明医科大学》2015年硕士论文

【摘要】：目的：高脂高糖饮食结合小剂量链脉佐菌素诱导2型糖尿病模型,观察糖尿病状态下大鼠骨代谢的特点,探讨GLP-1类似物(利拉鲁肽)对2型糖尿病大鼠骨代谢的影响。方法：选SPF级健康雄性SD大鼠90只,随机分为20只为正常对照组(NC组),实验组70只。高脂高糖饮食联合小剂量链脉菌素(STZ)诱导建立2型糖尿病大鼠模型,成模的大鼠按血糖进行区组随机化分为3组,利拉鲁肽低剂量(400ug/kg)干预组(LR-L)：18只,利拉鲁肽高剂量(800ug/kg)干预组(LR-H)：18只,按其剂量每日皮下注射利拉鲁肽,糖尿病未治疗组(DM)：19只,DM组、NC组以等量生理盐水皮下注射,共干预4周,每周监测各组大鼠的血糖、体重并记录,同时观察其饮食情况以及精神状态。至实验结束时,采用DEXA法检测大鼠骨密度,收集大鼠血清,检测大鼠血糖、血脂、胰岛素抵抗相关指标、骨代谢相关指标,制作骨组织病理学切片。结果：诱导2型糖尿病大鼠58只,造模率为：83%,①体重：实验结束时,NC组DM组LR-L、LR-H组,差异具体统计学意义(P0.05)；②糖代谢相关指标：LR-H、LR-L、DM组大鼠FBG、TG、TCH较NC组均明显升高(P0.05),LR-L组FBG、TCH、TG低于DM组,LR-H组FBG、TCH低于DM组,差异有统计学意义(P0.05)；药物干预前,DM、LR-L、LR-H组FIS、HOMA-IR明显高于NC组,ISI明显小于NC组,差异有统计学意义(P0.05),利拉鲁肽干预4周后,LR-H、LR-L组HOMA-IR明显低于DM组,ISI明显高于DM组,差异具有统计学意义(P0.05),LR-H与LR-L之间FIS、HOMA-IR、ISI均无明显差异,LR-L、LR-H组药物干预4周后HOMA-IR均明显较前下降,ISI有所升高,差异有统计学意义(P0.05)；③肝指数：DM组大鼠肝指数较NC组重(P0.01), LR-H与LR-L组肝指数介于两者之间,且明显低于DM组,差异具有统计学意义(P0.01),LR-H组肝指数明显低于LR-L组(P0.01)；④四组间组血清P、Ca、CTX-1、BGP无明显差异(P0.05)；DM组ALP高于NC组,差异有统计学意义(P0.01),LR-L组ALP低于DM组,差异有统计学意义；⑤骨密度：DM、LR-L、LR-H组大鼠骨密度均低于NC,差异具有统计学意义(P0.05),LR-H及LR-L组大鼠骨密度介于NC组与DM组之间,与DM组比较差异无统计学意义；⑥ DM、LR-H、LR-L组血清OPG、RANKL明显高于NC组,DM组血清SO明显高于NC组,差异具有统计学意义(P0.05),LR-L、LR-L组血清OPG、RANKL、SO介于NC与DM之间,且LR-H组OPG明显高于DM组,LR-H与LR-L组RANKL明显低于DM组,差异有统计学意义(P0.05)；DM组血清OPG/RANKL比率明显低于NC组,LR-L、LR-H组血清OPG/RANKL较DM明显升高,差异具有统计学意义(P0.05)；⑦HE染色：NC组骨小梁排列密集,宽度正常、均匀,连续性好,成网状连接,骨小梁间距较小。DM与NC组相比,骨小梁变细、数量减少,连续性破坏,游离断增多,骨小梁间距增大,LR-L、LR-H组介于NC组与DM组之间,骨小梁宽度减小,排列整齐,连续性较好,断端较少,骨小梁间距减少,与NC组接近,但LR-L与LR-H之间未见明显异常。结论：1)高脂高糖喂养SD大鼠5周后一次性腹腔注射STZ35mg/kg,可以建立稳定的具有高血糖、高血脂、高胰岛素血症和胰岛素抵抗为特征的2型糖尿病动物模型,与人类2型糖尿病的临床特点相似,是研究人类2型糖尿病较理想的动物模型。2)高脂高糖饮食结合小剂量STZ诱导的2型糖尿病大鼠骨密度下降,骨病理学提示骨吸收增加的结构改变,但骨代谢指标血清BGP、CTX-1无明显变化,而血清SO及ALP水平升高。3)利拉鲁肽可降低2型糖尿病大鼠的空腹血糖,改善胰岛素抵抗,增加胰岛素敏感性,降低血清TC、TG、RANKL水平,升高血清OPG的含量,具有明显的降体重作用。4)骨病理形态学检查提示糖尿病大鼠骨吸收增加,利拉鲁肽可抑制糖尿病大鼠骨吸收,利拉鲁肽干预未见糖尿病大鼠骨密度的提高。
[Abstract]:Objective : To investigate the effects of high - fat and high - sugar diet combined with low - dose streptozocin on bone metabolism in rats with type 2 diabetes mellitus . Methods : Ninety - nine healthy male SD rats were randomly divided into three groups .
( 2 ) The correlation indexes of glucose metabolism : LR - H , LR - L , FBG , TG , TCH in DM group were significantly higher than those in NC group ( P0.05 ) , FBG , TCH , TG in LR - L group were lower than that in DM group , FBG and TCH in LR - L group were lower than that in DM group , and the difference was statistically significant ( P0.05 ) ;
There was no significant difference between LR - H and LR - L in patients with DM , LR - L , LR - H and LR - L than those in the DM group ( P0.05 ) . In the LR - L and LR - L groups , there was no significant difference between LR - H and LR - L .
( 3 ) The liver index of the DM group was significantly lower than that in the NC group ( P0.01 ) , and the liver index of LR - H and LR - L groups was significantly lower than that in the DM group ( P0.01 ) .
There was no significant difference in serum P , Ca , CTX - 1 and BGP among the four groups ( P0.05 ) .
ALP in DM group was higher than that in NC group ( P0.01 ) . ALP in LR - L group was lower than that in DM group .
( 5 ) Bone mineral density : DM , LR - L , LR - H group had lower bone mineral density than NC group ( P0.05 ) . The bone mineral density of LR - H and LR - L group was between NC group and DM group .
The serum levels of OPG and RANKL in DM , LR - H , LR - L groups were significantly higher than those in NC group . The serum levels of OPG , RANKL and SO were significantly higher in DM group than in NC group ( P0.05 ) . In LR - H group , OPG was significantly higher in LR - L group than in DM group , and that of LR - H and LR - L group were significantly lower than that in DM group , and there was significant difference in LR - H and LR - L groups ( P0.05 ) .
The serum OPG / RANKL ratio in DM group was significantly lower than that in NC group , LR - L and LR - H group , and the level of OPG / RANKL increased significantly in LR - L and LR - H group ( P0.05 ) .
Conclusion : 1 ) High - fat and high - sugar diet combined with low - dose - induced diabetic rats ' bone mineral density decreased , the bone trabecular distance increased , the level of LR - L and LR - H was close to NC group , but the level of serum SO and ALP increased .

【学位授予单位】：昆明医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R587.1;R580

【参考文献】