【摘要】： 目的：觀察28周高脂飲食對(duì)SD大鼠外周組織胰島素敏感性及血管內(nèi)皮舒張功能的影響。 方法：41只SD雄性大鼠隨機(jī)分為高脂飼料喂養(yǎng)組(HF，n=21)和普通飼料喂養(yǎng)組(NC，n=20)，喂養(yǎng)28周后，做以下檢查：(1)體重及腹內(nèi)脂肪稱重：(2)采血檢測(cè)空腹血糖(FBG)、胰島素(FINS)、游離脂肪酸(FFA)、甘油三酯(TG)等：(3)正常血糖高胰島素鉗夾試驗(yàn)評(píng)價(jià)外周胰島素抵抗程度和(4)取出主動(dòng)脈置于器官浴槽中，平衡后先經(jīng)PGF2α預(yù)收縮，再分別加入乙酰膽堿及硝普鈉，觀察主動(dòng)脈環(huán)對(duì)其舒張反應(yīng)。 結(jié)果：(1) 28周時(shí)HF組體重及腹內(nèi)脂肪含量升高：(2)與NC組相比，HF組血FBG和FINS水平增高，血FFA和TG也明顯增高(p＜0.05)；(3) HF組葡萄糖輸注率(GIR)為3.60±1.2 mg·min~(-1)·kg~(-1)，，明顯低于NC組11.94±1.7mg·min~(-1)·kg~(-1)(p＜0.01)；(4)與NC組相比，HF組內(nèi)皮依賴性血管舒張(EDV)明顯降低(81.3±3.1％vs 35.2±2.4％，p＜0.01)，而非內(nèi)皮依賴性血管舒張(NEDV)兩組無明顯差別(85.4±3.2％vs 72.3±2.2％，p＞0.05)和(5)相關(guān)分析顯示：HF組腹內(nèi)脂肪重量及血FFA水平與GIR呈負(fù)相關(guān)，HF組血FFA水平與內(nèi)皮依賴性血管舒張(EDV)呈負(fù)相關(guān)。 結(jié)論：長(zhǎng)期高脂喂養(yǎng)可導(dǎo)致大鼠外周組織胰島素抵抗和內(nèi)皮依賴性血管舒張功能受損，其機(jī)理與長(zhǎng)期高脂喂養(yǎng)導(dǎo)致大鼠血FFA水平升高有關(guān)。 目的：觀察28周高脂飼養(yǎng)對(duì)SD大鼠主動(dòng)脈內(nèi)皮依賴性血管舒張功能影響的機(jī)制。 方法：8周齡雄性SD大鼠41只隨機(jī)分為2組：正常飼料喂養(yǎng)組(NC，n=20)和高脂飼料喂養(yǎng)組(HF，n=21)，喂養(yǎng)28周后，做以下檢查：(1)采血檢測(cè)MDA、GSH水平；(2)檢測(cè)C-反應(yīng)蛋白(CRP)水平；(3)檢測(cè)血管細(xì)胞間粘附因子-1(sVCAM-1)水平：(4)評(píng)價(jià)離體主動(dòng)脈環(huán)對(duì)乙酰膽堿及硝普鈉的舒張反應(yīng)和(5)采用熒光定量PCR檢測(cè)主動(dòng)脈內(nèi)皮細(xì)胞eNOSmRNA表達(dá)。 結(jié)果：(1)與NC組相比，HF組血MDA水平明顯增高(16.86±4.5 vs26.63±5.0 nmol／ml，p＜0.01)，血GSH水平降低(124.10±34.7 vs84.78±21.0mg／ml，p＜0.01)；(2) HF組血CRP水平高于NC組(0.71±0.23mg／L vs 0.53±0.14 mg／L，p＜0.05)；(3)與NC組相比，HF組血sVCAM-1水平明顯增高(344.1±84.5 vs 465.3±124.6ng／mlnmol／ml，p＜0.01)；(4)與NC組相比，HF組內(nèi)皮依賴性血管舒張(EDV)明顯降低(81.3±3.1％vs 35.2±2.4％，p＜0.01)，而非內(nèi)皮依賴性血管舒張(NEDV)兩組無明顯差別(85.4±3.2％vs 72.3±2.2％，p＞0.05)和(5)與NC組相比，HF組主動(dòng)脈eNOSmRNA表達(dá)降低了34％。 結(jié)論：長(zhǎng)期高脂飼養(yǎng)SD大鼠存在內(nèi)皮依賴性血管舒張功能減低，可能是高FFA血癥抑制血管內(nèi)皮細(xì)胞eNOS表達(dá)而引起內(nèi)皮細(xì)胞NO產(chǎn)生和釋放減少所致，其機(jī)制與FFA所誘導(dǎo)的氧化應(yīng)激和炎癥反應(yīng)有關(guān)。
[Abstract]:Aim: to observe the effects of 28 weeks high fat diet on insulin sensitivity and vascular endothelial diastolic function in peripheral tissues of SD rats. Methods: 41 male SD rats were randomly divided into high fat diet (HF,n=21) group and general feed feeding (NC,n=20) group. Do the following tests: (1) body weight and abdominal fat weighing; (2) fasting blood glucose, (FBG), insulin, (FINS), free fatty acid, (FFA), triglyceride (TG) et al; (3) normal hyperglycemic hyperinsulinemic clamp test to evaluate the degree of peripheral insulin resistance; (4) Take out the aorta and put it in an organ bath. After equilibrium, the aortic rings were precontracted by PGF2 偽, then acetylcholine and sodium nitroprusside were added respectively to observe the diastolic response of aortic rings. Results: (1) after 28 weeks, the body weight and abdominal fat content in HF group increased: (2) compared with NC group, the serum FBG and FINS levels in HF group were higher than those in NC group (p < 0. 05); (3). The (GIR) infusion rate in HF group was 3.60 鹵1.2 mg min~ (-1) kg~ (-1), which was significantly lower than that in NC group (11.94 鹵1.7mg min~ (-1) kg~ (-1) (p < 0.01). (4) compared with NC group, (EDV) of endothelium-dependent vasodilation in HF group was significantly lower than that in NC group (81.3 鹵3.1%vs 35.2 鹵2.4, p < 0.01), but there was no significant difference between HF group and non-endothelium-dependent vasodilation (NEDV) group (85.4 鹵3.2%vs 72.3 鹵2.2, P > 0.05). Fat weight and serum FFA level were negatively correlated with GIR, and FFA levels were negatively correlated with endothelium-dependent vasodilation (EDV) in HF group. Conclusion: Long-term high fat feeding can lead to insulin resistance in peripheral tissues and impaired endothelium-dependent vasodilation function in rats. The mechanism is related to the increase of FFA level in blood of rats induced by long-term high fat feeding. Aim: to observe the mechanism of 28 weeks high fat feeding on endothelium-dependent vasodilation of aorta in SD rats. Methods: Forty-one 8-week-old male SD rats were randomly divided into two groups: normal feed feeding group (NC,n=20) and high-fat feed feeding group (HF,n=21). After 28 weeks of feeding, the following examinations were performed: (1) the level of MDA,GSH was detected by blood collection, (2) the level of C-reactive protein (CRP) was detected. (3) the levels of vascular intercellular adhesion factor-1 (sVCAM-1) were measured: (4) the relaxation response of isolated aortic rings to acetylcholine and sodium nitroprusside was evaluated; (5) the expression of eNOSmRNA in aortic endothelial cells was detected by fluorescence quantitative PCR. Results: (1) compared with the NC group, the serum MDA level in the HF group was significantly higher (16.86 鹵4.5 vs26.63 鹵5.0 nmol/ml,p < 0. 01) and the serum GSH level was decreased (124.10 鹵34.7 vs84.78 鹵21.0 mg / ml); (2). The CRP level in the HF group was higher than that in the NC group (0. 71 鹵0.23mg/L vs 0. 53 鹵0. 14 mg/L,p < 0. 05). (3) compared with NC group, the serum sVCAM-1 level in HF group was significantly higher than that in NC group (344.1 鹵84.5 vs, 465.3 鹵124.6 ngmol / ml, P < 0. 01). (4) compared with NC group, (EDV) of endothelium-dependent vasodilation in HF group was significantly lower than that in NC group (81.3 鹵3.1%vs 35.2 鹵2.4, p < 0.01), but there was no significant difference between (NEDV) group and non-endothelium-dependent vasodilation (NEDV) group (85.4 鹵3.2%vs 72.3 鹵2.2, P > 0.05) and (5) compared with NC group, aortic eNOSmRNA in HF group was significantly lower than that in NC group. The expression was reduced by 34%. Conclusion: there is a decrease in endothelium-dependent vasodilation function in SD rats fed with hyperlipidemia for a long time, which may be due to the inhibition of eNOS expression in vascular endothelial cells by hyperlipidemia and the decrease of NO production and release in endothelial cells. Its mechanism is related to oxidative stress and inflammation induced by FFA.
【學(xué)位授予單位】：中國(guó)協(xié)和醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2006
【分類號(hào)】：R363

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