本文選題：西羅莫司 + 脂肪酸�。� 參考：《重慶醫(yī)科大學(xué)學(xué)報(bào)》2017年07期

【摘要】：目的:研究西羅莫司對(duì)小鼠肝臟脂質(zhì)積聚的影響及機(jī)制初探。方法:6~8周齡雄性C57BL/6J小鼠,隨機(jī)分為3組:A組為普通飲食組(n=12),B組為高脂飲食組(n=9),C組為高脂飲食加隔天注射西羅莫司組(n=7),喂養(yǎng)14周。全自動(dòng)生化分析儀檢測(cè)血清生化指標(biāo)。酶聯(lián)免疫吸附法和酶偶聯(lián)比色法分別檢測(cè)肝臟游離脂肪酸(free fatty acid,FFA)和甘油三酯(triglyceride,TG)的含量。Western blot檢測(cè)脂肪酸轉(zhuǎn)運(yùn)酶(fatty acid translocase,FAT/CD36)蛋白的表達(dá)水平。熒光顯微鏡觀察原代肝細(xì)胞對(duì)熒光標(biāo)記FFA的動(dòng)態(tài)攝取。結(jié)果:與A組相比,B組小鼠體質(zhì)量(q=6.68,P=0.000),血清TG(q=4.88,P=0.045),高密度脂蛋白(high-density lipoprotein,HDL)(q=6.311,P=0.002),谷草轉(zhuǎn)氨酶(aspirate aminotransferase,AST)(q=8.84,P=0.001)水平明顯增高,肝臟組織TG(q=14.4,P=0.000),FFA(q=18.0,P=0.000)也明顯增高。C組小鼠較B組體質(zhì)量(q=7.99,P=0.000),血清TG(q=4.636,P=0.050),AST(q=5.16,P=0.016)及肝臟TG(q=8.91,P=0.000)和FFA(q=14.1,P=0.000)都顯著降低。Western blot結(jié)果顯示C組小鼠肝臟CD36的蛋白表達(dá)水平較B組明顯降低。FFA動(dòng)態(tài)攝取實(shí)驗(yàn)通過(guò)定量熒光強(qiáng)度顯示西羅莫司能明顯抑制肝細(xì)胞對(duì)FFA的攝取速度(各時(shí)間點(diǎn)P均0.05)。結(jié)論:西羅莫司能抑制肝細(xì)胞對(duì)外源性FFA的攝取,減輕肝臟脂質(zhì)積聚,其作用機(jī)制可能與CD36相關(guān)。
[Abstract]:Objective: to study the effect and mechanism of sirolimus on lipids accumulation in mice. Methods male C57BL/6J mice at the age of 6 to 8 weeks were randomly divided into 3 groups: group A, normal diet group, group B, group B, high fat diet group, group C, high fat diet plus sirolimus group for the next day, fed for 14 weeks. The serum biochemical indexes were detected by automatic biochemical analyzer. The content of free fatty acid (FFA) and triglyceride triglyceride (TGG) in liver were detected by enzyme-linked immunosorbent assay (Elisa) and enzyme-coupled colorimetry (Elisa) respectively. Western blot was used to detect the expression of fatty acid translocase / FATP / CD36 protein. Fluorescence microscopy was used to observe the dynamic uptake of fluorescent labeled FFA in primary hepatocytes. Results: compared with group A, the body weight of mice in group B was significantly higher than that in group A (P 0.000), the levels of serum TGQ, 4.88 and 0.045, high density lipoprotein, high density lipoprotein, high density lipoprotein, high density lipoprotein, high density lipoprotein, and aspartate aminotransferase ASA, 8.84, P0. 001 were significantly higher in group B than in group A (P < 0.05), and the levels of high density lipoprotein in group B were significantly higher than those in group A (P < 0.05). Liver tissue (TGQN 14.4P0.000) and FFAq14.1P0.000) also significantly increased compared with group B. the expression of CD36 protein in group C was significantly lower than that in group B, and the level of serum TGGQ (4.636), ASTq5.16P0.016) and liver TGQ (8.91) and FFAq14.1P0.000) were significantly decreased. The results of Western blot showed that the protein expression level of liver CD36 in group C was significantly lower than that in group B (P 0.016). The results of Western blot showed that the protein expression level of liver CD36 in group C was significantly lower than that in group B (P < 0.01). The results of Western blot showed that the protein expression level of liver CD36 in group C was significantly lower than that in group B (P < 0.01). The results of Western blot showed that the protein expression of liver CD36 in group C was significantly lower than that in group B. The over-quantitative fluorescence intensity showed that sirolimus could significantly inhibit the uptake of FFA by hepatocytes (P < 0.05). Conclusion: sirolimus can inhibit the uptake of exogenous FFA and alleviate the accumulation of lipids in liver cells. The mechanism of sirolimus may be related to CD36.
【作者單位】： 重慶醫(yī)科大學(xué)脂糖代謝性疾病重慶市重點(diǎn)實(shí)驗(yàn)室;
【基金】：國(guó)家自然科學(xué)基金資助項(xiàng)目(編號(hào):81400786) 重慶市科委基礎(chǔ)與前沿研究計(jì)劃資助項(xiàng)目(編號(hào):cstc2015jcyj A10001)
【分類號(hào)】：R575.5

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