本文選題：2型糖尿病 + 大鼠��； 參考：《昆明醫(yī)科大學》2015年碩士論文

【摘要】：目的：高脂高糖飲食結合小劑量鏈脈佐菌素誘導2型糖尿病模型,觀察糖尿病狀態(tài)下大鼠骨代謝的特點,探討GLP-1類似物(利拉魯肽)對2型糖尿病大鼠骨代謝的影響。方法：選SPF級健康雄性SD大鼠90只,隨機分為20只為正常對照組(NC組),實驗組70只。高脂高糖飲食聯(lián)合小劑量鏈脈菌素(STZ)誘導建立2型糖尿病大鼠模型,成模的大鼠按血糖進行區(qū)組隨機化分為3組,利拉魯肽低劑量(400ug/kg)干預組(LR-L)：18只,利拉魯肽高劑量(800ug/kg)干預組(LR-H)：18只,按其劑量每日皮下注射利拉魯肽,糖尿病未治療組(DM)：19只,DM組、NC組以等量生理鹽水皮下注射,共干預4周,每周監(jiān)測各組大鼠的血糖、體重并記錄,同時觀察其飲食情況以及精神狀態(tài)。至實驗結束時,采用DEXA法檢測大鼠骨密度,收集大鼠血清,檢測大鼠血糖、血脂、胰島素抵抗相關指標、骨代謝相關指標,制作骨組織病理學切片。結果：誘導2型糖尿病大鼠58只,造模率為：83%,①體重：實驗結束時,NC組DM組LR-L、LR-H組,差異具體統(tǒng)計學意義(P0.05)；②糖代謝相關指標：LR-H、LR-L、DM組大鼠FBG、TG、TCH較NC組均明顯升高(P0.05),LR-L組FBG、TCH、TG低于DM組,LR-H組FBG、TCH低于DM組,差異有統(tǒng)計學意義(P0.05)；藥物干預前,DM、LR-L、LR-H組FIS、HOMA-IR明顯高于NC組,ISI明顯小于NC組,差異有統(tǒng)計學意義(P0.05),利拉魯肽干預4周后,LR-H、LR-L組HOMA-IR明顯低于DM組,ISI明顯高于DM組,差異具有統(tǒng)計學意義(P0.05),LR-H與LR-L之間FIS、HOMA-IR、ISI均無明顯差異,LR-L、LR-H組藥物干預4周后HOMA-IR均明顯較前下降,ISI有所升高,差異有統(tǒng)計學意義(P0.05)；③肝指數(shù)：DM組大鼠肝指數(shù)較NC組重(P0.01), LR-H與LR-L組肝指數(shù)介于兩者之間,且明顯低于DM組,差異具有統(tǒng)計學意義(P0.01),LR-H組肝指數(shù)明顯低于LR-L組(P0.01)；④四組間組血清P、Ca、CTX-1、BGP無明顯差異(P0.05)；DM組ALP高于NC組,差異有統(tǒng)計學意義(P0.01),LR-L組ALP低于DM組,差異有統(tǒng)計學意義；⑤骨密度：DM、LR-L、LR-H組大鼠骨密度均低于NC,差異具有統(tǒng)計學意義(P0.05),LR-H及LR-L組大鼠骨密度介于NC組與DM組之間,與DM組比較差異無統(tǒng)計學意義；⑥ DM、LR-H、LR-L組血清OPG、RANKL明顯高于NC組,DM組血清SO明顯高于NC組,差異具有統(tǒng)計學意義(P0.05),LR-L、LR-L組血清OPG、RANKL、SO介于NC與DM之間,且LR-H組OPG明顯高于DM組,LR-H與LR-L組RANKL明顯低于DM組,差異有統(tǒng)計學意義(P0.05)；DM組血清OPG/RANKL比率明顯低于NC組,LR-L、LR-H組血清OPG/RANKL較DM明顯升高,差異具有統(tǒng)計學意義(P0.05)；⑦HE染色：NC組骨小梁排列密集,寬度正常、均勻,連續(xù)性好,成網(wǎng)狀連接,骨小梁間距較小。DM與NC組相比,骨小梁變細、數(shù)量減少,連續(xù)性破壞,游離斷增多,骨小梁間距增大,LR-L、LR-H組介于NC組與DM組之間,骨小梁寬度減小,排列整齊,連續(xù)性較好,斷端較少,骨小梁間距減少,與NC組接近,但LR-L與LR-H之間未見明顯異常。結論：1)高脂高糖喂養(yǎng)SD大鼠5周后一次性腹腔注射STZ35mg/kg,可以建立穩(wěn)定的具有高血糖、高血脂、高胰島素血癥和胰島素抵抗為特征的2型糖尿病動物模型,與人類2型糖尿病的臨床特點相似,是研究人類2型糖尿病較理想的動物模型。2)高脂高糖飲食結合小劑量STZ誘導的2型糖尿病大鼠骨密度下降,骨病理學提示骨吸收增加的結構改變,但骨代謝指標血清BGP、CTX-1無明顯變化,而血清SO及ALP水平升高。3)利拉魯肽可降低2型糖尿病大鼠的空腹血糖,改善胰島素抵抗,增加胰島素敏感性,降低血清TC、TG、RANKL水平,升高血清OPG的含量,具有明顯的降體重作用。4)骨病理形態(tài)學檢查提示糖尿病大鼠骨吸收增加,利拉魯肽可抑制糖尿病大鼠骨吸收,利拉魯肽干預未見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 .

【學位授予單位】：昆明醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2015
【分類號】：R587.1;R580

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