本文選題：高脂血癥 + 殼聚糖�。� 參考：《廣東藥學(xué)院》2014年碩士論文

【摘要】：高脂血癥是一種嚴(yán)重危害人類健康的全身脂質(zhì)代謝異常疾病，是心腦血管疾病的重要危險因素，隨著現(xiàn)代飲食和生活方式的轉(zhuǎn)變，高脂血癥已經(jīng)成為全球性公共衛(wèi)生問題。目前以化學(xué)藥物治療為主，但存在多種嚴(yán)重不良反應(yīng)。開發(fā)安全、有效、不良反應(yīng)少的天然降血脂藥物意義重大。 殼聚糖（CTS）是從蝦蟹殼中提取出的帶正電荷的堿性多糖，具有良好的生物相容性和生物可降解性，大量體內(nèi)外實(shí)驗證明殼聚糖具有良好的降脂和減肥活性。但其水溶性差需大劑量服用，易產(chǎn)生惡心、嘔吐和便秘等副作用。課題組成員前期將其制備成分散性好、利用度高的殼聚糖微球（CTMS）以及載辣椒堿的殼聚糖微球（CCMS），達(dá)到了增強(qiáng)活性和降低副作用的目的。殼寡糖（COSII和COSI）和氨基葡萄糖（GLC）是殼聚糖的降解產(chǎn)物，水溶性高、易吸收且無毒副作用。 本實(shí)驗研究CTS及相關(guān)產(chǎn)物對油酸誘導(dǎo)的HepG2細(xì)胞內(nèi)脂質(zhì)堆積的作用，，MTT法確定安全給藥濃度范圍，油紅O染色后觀察細(xì)胞形態(tài)和脂滴分布，提取油紅O定量脂質(zhì)含量，測定細(xì)胞內(nèi)TG含量。結(jié)果表明，CTS、CTMS、CCMS、COSII、COSI和GLC均可有效抑制HepG2細(xì)胞內(nèi)的脂質(zhì)堆積，顯著降低細(xì)胞內(nèi)TG含量，呈劑量依賴性。 采用高脂飲食誘導(dǎo)高脂血癥大鼠模型，研究CTS及降解產(chǎn)物的降脂藥效活性。結(jié)果表明，CTS、COSII和GLC可不同程度的減緩高脂血癥大鼠的體重、脂體比、Lee's指數(shù)、臟器指數(shù)的增長，抑制脂肪細(xì)胞的生長，具有一定的減肥活性，呈劑量依賴性；可顯著降低血清TC、TG和LDL-C含量；減少肝臟中TC和TG含量、增加總膽汁酸（TBA）含量，促進(jìn)糞便中TC、TG和TBA的排泄，發(fā)揮降脂作用。COSII、GLC可不同程度的提高高脂血癥大鼠SOD酶活性，具有抗氧化作用。CTS、COSII和GLC可顯著降低高脂血癥大鼠血清和肝臟中AST、ALT的含量，不同程度地緩解脂肪肝癥狀，具有保肝護(hù)肝作用。 為進(jìn)一步研究CTS及相關(guān)物質(zhì)降脂活性的作用機(jī)理，通過Western Blot技術(shù)檢測其對HepG2細(xì)胞內(nèi)脂質(zhì)代謝相關(guān)的肝脂酶（HL）和過氧化物酶體增殖物激活受體α（PPARα）的蛋白表達(dá)。結(jié)果顯示，CTMS可促進(jìn)HepG2細(xì)胞內(nèi)HL蛋白和PPARα蛋白的表達(dá)，而CTS、CCMS、COSII、COSI和GLC對其表達(dá)基本無影響；抑制PPARα基因表達(dá)，可顯著抑制HL蛋白表達(dá)，表明CTMS促進(jìn)HL蛋白表達(dá)與PPARα基因有關(guān)；在高TC、TG條件下，CTMS干預(yù)后對HL蛋白和PPARα蛋白表達(dá)均有促進(jìn)作用，抑制PPARα基因后，上述作用消失，說明CTMS促進(jìn)HL蛋白表達(dá)影響可能是先通過促進(jìn)PPARα表達(dá)實(shí)現(xiàn)。
[Abstract]:Hyperlipidemia is a serious disease of lipid metabolism and an important risk factor of cardiovascular and cerebrovascular diseases. With the change of modern diet and lifestyle, hyperlipidemia has become a global public health problem. At present, chemotherapeutic therapy is the main treatment, but there are many serious adverse reactions. It is of great significance to develop natural hypolipidemic drugs that are safe, effective and less adverse. Chitosan (CTS) is a positively charged alkaline polysaccharide extracted from shrimp and crab shell. It has good biocompatibility and biodegradability. A large number of experiments in vivo and in vitro have proved that chitosan has good lipid-lowering and weight loss activities. However, its poor water-solubility needs a large dose, easy to produce nausea, vomiting and constipation and other side effects. In the early stage, the chitosan microspheres (CTMSs) with good dispersity and high availability and capsaicin loaded chitosan microspheres (CCMSS) were prepared, which achieved the purpose of enhancing the activity and reducing the side effects. Chito-oligosaccharide (COSII and COSI) and glucosamine (GLC) are the degradation products of chitosan, which have high water solubility, easy absorption and no toxic side effects. The effect of CTS and its related products on lipid accumulation in HepG2 cells induced by oleic acid was studied in this experiment. The safe range of administration concentration was determined by MTT method. After oil red O staining, cell morphology and lipid droplet distribution were observed, and the quantitative lipid content of oil red O was extracted. The content of TG in cells was measured. The results showed that both CTS and GLC could effectively inhibit lipid accumulation in HepG2 cells and decrease the content of TG in a dose-dependent manner. Hyperlipidemic rat model was induced by high fat diet to study the antilipidemic effect of CTS and its degradation products. The results showed that CTSS-COSII and GLC could decrease the body weight, fat / body ratio, Leehs index and viscera index of hyperlipidemia rats, inhibit the growth of adipocytes, and have a certain weight loss activity in a dose-dependent manner. TC and TG contents in liver, total bile acid (TBA) content and excretion of TCTG and TBA in feces were significantly decreased, and the activity of SOD in hyperlipidemia rats was increased in different degree. The results showed that the antioxidative activity. CTSS-COSII and GLC could significantly reduce the alt content in serum and liver of rats with hyperlipidemia, relieve the symptoms of fatty liver in varying degrees, and protect the liver and liver of hyperlipidemic rats. In order to study the mechanism of lipid lowering activity of CTS and its related substances, the expression of lipopolipase HL1 and peroxisome proliferator-activated receptor 偽 -PPAR- 偽) in HepG2 cells was detected by Western Blot technique. The results showed that CTMS could promote the expression of HL protein and PPAR 偽 protein in HepG2 cells, but the expression of PPAR 偽 gene was not affected by CTS- CCMS CS-III-COSI and GLC, and the expression of HL protein was significantly inhibited by inhibiting the expression of PPAR 偽 gene, indicating that the expression of HL protein promoted by CTMS was related to PPAR 偽 gene. Under the condition of high TCT-TG, the expression of HL protein and PPAR 偽 protein were promoted by CTMS. After inhibiting PPAR 偽 gene, the above effects disappeared, which suggested that the effect of CTMS on HL protein expression might be achieved by promoting PPAR 偽 expression first.
【學(xué)位授予單位】：廣東藥學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R96

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本文編號：1932010