發(fā)布時(shí)間：2018-05-09 20:09

  本文選題：糖耐量低減 + 胰島素抵抗��； 參考：《黑龍江中醫(yī)藥大學(xué)》2017年博士論文

【摘要】：研究目的建立單純高脂飲食誘導(dǎo)的IGT大鼠模型,在此基礎(chǔ)上觀察化瘀溫膽湯對(duì)高脂誘導(dǎo)大鼠外觀表現(xiàn)和醫(yī)學(xué)病理特征的影響。闡明化瘀溫膽湯改善I R和能量代謝的機(jī)制,為探尋其作用靶點(diǎn)提供實(shí)驗(yàn)依據(jù)。研究方法健康Wistar雄性大鼠,隨機(jī)分兩組,正常組給予普通飼料喂養(yǎng),其余大鼠給予高脂飼料喂養(yǎng),共持續(xù)20w,誘導(dǎo)IGT模型。觀察大鼠外觀表現(xiàn),行IPGTT檢測(cè)血糖,測(cè)定FPG及2hPG。模型復(fù)制成功后,隨機(jī)分為模型組、中藥組、西藥組,中藥組給予5.2g/kg·d化瘀溫膽湯,西藥組給予99 mg/kg·d二甲雙胍溶液,正常組和模型組給予同體積生理鹽水。連續(xù)灌胃給藥4w。實(shí)驗(yàn)結(jié)束后,腹主動(dòng)脈取血,分離血清,ELISA法檢測(cè)Fins、G SP、ADPN、LEP,計(jì)算IAI、IRI,生化分析儀檢測(cè)HDL-C、LDL-C。稱取肝臟質(zhì)量,計(jì)算肝臟指數(shù)。肝組織勻漿,檢測(cè)TG、TC、LPO、GSH-Px水平。行肝臟糖原染色觀察糖原儲(chǔ)備情況,圖像分析軟件分析陽性目標(biāo)面密度和平均灰度。Realtime PCR法檢測(cè)肝臟AMPK信號(hào)通路中AMPKα、A CCα mRNA的表達(dá)。Western Blot法檢測(cè)AMPKα、p-AMPKα、ACCα、p-ACCα蛋白的表達(dá)。研究結(jié)果1.血糖、血脂、胰島素相關(guān)指標(biāo):化瘀溫膽湯減輕體重,降低大鼠F PG、2hPG,與模型組比較有統(tǒng)計(jì)學(xué)意義(p0.05或p0.01),降低FPG存在時(shí)效性�；�瘀溫膽湯降低Fins、IRI、GSP水平,提高IAI水平,與模型組比較有統(tǒng)計(jì)學(xué)意義(p0.05)�；�瘀溫膽湯提高血清HDL-C水平、降低L DL-C水平,與模型組比較有統(tǒng)計(jì)學(xué)意義O?0.01)。2.細(xì)胞因子:化瘀溫膽湯提高血清ADPN水平、降低LEP水平,與模型組比較有顯著性差異(p0.01)。3.肝臟糖脂代謝及氧化應(yīng)激指標(biāo):化瘀溫膽湯降低肝臟質(zhì)量、肝臟指數(shù),肝臟TG、TC水平,與模型組比較有統(tǒng)計(jì)學(xué)意義(p0.05或p0.01)�；�瘀溫膽湯降低LPO水平,提高GSH-Px水平,與模型組比較有統(tǒng)計(jì)學(xué)意義(p0.05或p0.01)�；�瘀溫膽湯提高陽性目標(biāo)面密度和平均灰度值,與模型組比較有顯著性差異(p0.01),增加肝臟糖原儲(chǔ)備。4.肝臟AMPK信號(hào)通路:化瘀溫膽湯上調(diào)肝臟組織AMPKα mRNA表達(dá),與模型組比較差異有統(tǒng)計(jì)學(xué)意義(p0.05),對(duì)ACCα mRNA表達(dá)無影響(p0.05)。化瘀溫膽湯上調(diào)肝臟組織AMPKα、p-AMPKα、p-ACCα蛋白表達(dá),與模型組比較有統(tǒng)計(jì)學(xué)意義(p0.05或p0.01),對(duì)ACCα蛋蛋表達(dá)無明顯影響(p0.05)。結(jié)論1.化瘀溫膽湯能夠降低模型大鼠血糖及血脂水平,糾正糖脂代謝紊亂,改善IR。2.化瘀溫膽湯提高模型大鼠ADPN水平,降低LEP水平,改善能量代謝狀態(tài)。3.化瘀溫膽湯能夠減輕模型大鼠肝臟脂肪沉積,改善氧化應(yīng)激狀態(tài),增加肝臟糖原儲(chǔ)備,起到保護(hù)肝臟作用。4.化瘀溫膽湯能夠提高模型大鼠肝臟AMPK活性,抑制ACC活性,發(fā)揮抑制脂肪合成,增加脂肪酸氧化,改善能量代謝狀態(tài),增加胰島素敏感性作用。5.化瘀溫膽湯影響模型大鼠肝臟AMPK-ACC信號(hào)通路,是其改善IGT IR的作用靶點(diǎn)之一。
[Abstract]:Objective to establish IGT rat model induced by high fat diet and observe the effect of Huayu Wendan decoction on the appearance and medical pathological characteristics of rats induced by high fat diet. To elucidate the mechanism of Huayu Wendan decoction (Huayu Wendan decoction) in improving I R and energy metabolism. Methods healthy male Wistar rats were randomly divided into two groups: normal group were fed with normal diet and other rats were fed with high fat diet for 20 weeks to induce IGT model. The appearance of rats was observed, blood glucose was detected by IPGTT, FPG and 2 h PG were measured. After successful replication, the model group was randomly divided into three groups: model group, traditional Chinese medicine group, western medicine group, 5.2g/kg d Huayu Wendan decoction, western medicine group 99 mg/kg d metformin solution, normal group and model group were given the same volume of normal saline. The drug was continuously administered by gavage for 4 weeks. At the end of the experiment, the abdominal aorta blood was taken and the serum was separated by Elisa for the detection of Finsberg SPN ADPNN LEP, the IAI IRI was calculated, and the HDL-CU LDL-C was detected by biochemical analyzer. The liver mass was measured and the liver index was calculated. Liver tissue homogenate was used to detect the level of GSH-Px in TGV TCU. The glycogen reserve was observed by liver glycogen staining, and the expression of AMPK 偽 -A CC 偽 mRNA in liver AMPK signaling pathway was detected by image analysis software. The expression of AMPK 偽 -ACC 偽 -p-ACC 偽 protein in liver AMPK signaling pathway was detected by image analysis software and the expression of AMPK 偽 -p-AMPK 偽 -ACC 偽 -p-ACC 偽 protein was detected by Western Blot method. Results 1. Blood glucose, blood lipids, insulin related indexes: Huayu Wendan decoction to reduce body weight, reduce the rat F-PG2 hPG2, compared with the model group, compared with the model group, p0.05 or p0.01a, reduce the time effect of FPG. Huayu Wendan decoction decreased the level of IAI and increased the level of IAI, which had statistical significance compared with the model group. Huayu Wendan decoction increased serum HDL-C level and decreased L DL-C level, which had statistical significance compared with model group. Cytokines: Huayu Wendan decoction increased the level of serum ADPN and decreased the level of LEP, there was significant difference between the model group and the model group. Liver glucose and lipid metabolism and oxidative stress index: Huayu Wendan decoction decreased liver quality, liver index, liver TGG TC level, and compared with model group, there was significant difference between model group and model group (P 0.05 or p 0.01). Huayu Wendan decoction decreased the level of LPO and increased the level of GSH-Px, which had statistical significance compared with the model group (p0.05 or p0.01). Huayu Wendan decoction increased the positive target surface density and average gray value, compared with the model group, the difference was significant (p0.01), and increased liver glycogen reserve. 4. Liver AMPK signal pathway: Huayu Wendan decoction upregulated the expression of AMPK 偽 mRNA in liver tissue, which was significantly different from the model group, but had no effect on the expression of ACC 偽 mRNA. Huayu Wendan decoction upregulated the expression of AMPK 偽 -pACC 偽 protein in liver tissue, which had statistical significance compared with the model group (p0.05 or p0.01), but had no significant effect on the expression of ACC 偽 egg. Conclusion 1. Huayu Wendan decoction can reduce blood sugar and blood lipid level, correct glucose and lipid metabolism disorder and improve IR.2. Huayu Wendan decoction increased ADPN level, decreased LEP level and improved energy metabolism state of model rats. Huayu Wendan decoction can reduce hepatic fat deposition, improve oxidative stress, increase liver glycogen reserve and protect liver. Huayu Wendan decoction could increase AMPK activity, inhibit ACC activity, inhibit fat synthesis, increase fatty acid oxidation, improve energy metabolism and increase insulin sensitivity. Huayu Wendan decoction (Huayu Wendan decoction) affects AMPK-ACC signal pathway in liver of model rats and is one of the targets for improving IGT IR.
【學(xué)位授予單位】：黑龍江中醫(yī)藥大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2017
【分類號(hào)】：R285.5

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相關(guān)期刊論文 前10條

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本文編號(hào)：1867250