本文選題：胰島素抵抗 + 針刺　； 參考：《廣州中醫(yī)藥大學(xué)》2016年博士論文

【摘要】：第一部分文獻(xiàn)研究隨著生活水平提高、飲食架構(gòu)的變化,人類飲食相關(guān)疾病成為發(fā)展中國家及發(fā)達(dá)國家的潛在威脅。營養(yǎng)過剩的飲食習(xí)慣及以靜坐為主的工作模式導(dǎo)致現(xiàn)代人代謝類疾病的頻繁發(fā)展,最明顯的就是糖尿病(DM)。胰島素抵抗(IR)作為糖尿病的前驅(qū)狀態(tài),受到了現(xiàn)代研究的高度關(guān)注。而且作為高血壓、脂肪肝、多囊卵巢綜合癥等疾病的“共同土壤”,胰島素抵抗同時受到廣泛關(guān)注。目前研究表明,糖尿病發(fā)病率的增長趨勢正在逐年增長,嚴(yán)重危害人類健康。目前為止,對現(xiàn)代醫(yī)學(xué)對2型糖尿病(T2DM)的發(fā)病機制尚未完全剖析清楚,胰島素抵抗和胰島素β細(xì)胞功能缺陷是其基本特征,而現(xiàn)代生活營養(yǎng)過剩所引起的肥胖、高血壓、糖尿病與胰島素抵抗關(guān)系密切。胰島素抵抗作為T2DM發(fā)生的核心環(huán)節(jié),是治療T2DM及胰島素抵抗相關(guān)疾病的關(guān)鍵。因此,調(diào)節(jié)胰島素信號通路異常,從而改善胰島素抵抗,以此為突破口,是治療T2DM的關(guān)鍵所在。中醫(yī)又將糖尿病稱為消渴病,歷史記載由來已久,因此歷代醫(yī)家及后世學(xué)者都在治療消渴病的過程中積累了豐富的臨床經(jīng)驗,或以之撰寫醫(yī)案分享臨床心得,或以之進(jìn)行實驗深化研究,都為人類的醫(yī)學(xué)事業(yè)作出了偉大的貢獻(xiàn)。大量文獻(xiàn)表明,針刺治療胰島素抵抗相關(guān)疾病過程中存在不可取代的優(yōu)勢,其作用機理與改善胰島素抵抗密切相關(guān)。本課題組通過既往研究發(fā)現(xiàn)針刺可通過受體及受體后水平改善胰島素抵抗。為了進(jìn)一步完善針刺改善胰島素抵抗的機理,本課題選擇胰島素抵抗發(fā)生、發(fā)展過程中的脂代謝紊亂作為切入點,以脂聯(lián)素所激發(fā)的AMPK-ACC信號轉(zhuǎn)導(dǎo)通路為研究方向,通過檢測相關(guān)指標(biāo)觀察針刺對胰島素抵抗從宏觀到微觀的整體性理論,進(jìn)一步證明其作用機理與治療作用。第二部分實驗研究目的：以高脂飲食誘導(dǎo)胰島素抵抗模型大鼠為研究對象,以噻唑烷二酮類藥物吡格列酮為對照,系統(tǒng)觀察針刺對胰島素抵抗大鼠血清脂聯(lián)素、游離脂肪酸含量的影響,肝臟AMPK、ACC蛋白表達(dá)的影響,以及肝臟超微結(jié)構(gòu)形態(tài)學(xué)的改變,從而多層次、多水平詮釋針刺對胰島素抵抗脂質(zhì)代謝紊亂的調(diào)節(jié)效應(yīng),為其強化胰島敏感功能提供新的理論基礎(chǔ)。方法：將52只雄性SPF級SD大鼠(180-220g)普通飼料適應(yīng)性飼養(yǎng)5天,隨機抽出10只為正常組,喂以普通飼料；余下大鼠改用高脂飼料喂養(yǎng)3個月為造模組。從第8周開始,每隔一周對所有大鼠進(jìn)行眼眶靜脈竇取血,檢測空腹血糖(FPG)、血漿胰島素(FINS),并計算胰島素敏感指標(biāo)(ISI、HOMA-IR),當(dāng)模型組大鼠ISI比空白組明顯降低(P0.05),HOMA-IR明顯升高(P0.05)時,即進(jìn)行高胰島素正葡萄糖鉗夾試驗,當(dāng)葡萄糖輸注率(GIR)與空白組相比明顯降低(P0.05)時為造模成功。第12周造模成功后,采用分層隨機法分為3組：模型組(11只)、西藥組(13只)、電針組(12只)。空白組繼續(xù)以普通飼料飼養(yǎng)2周,模型組繼續(xù)以高脂飼料飼養(yǎng)2周。電針組繼續(xù)以高脂飼料飼養(yǎng)2周,同時給予電針治療,穴取“豐隆”、“三陰交”,1次/日。西藥組續(xù)以高脂飼料飼養(yǎng)2周,同時給予吡格列酮懸濁液10mg/kg灌胃,1次/日。各組大鼠于治療結(jié)束后眼眶靜脈竇采血檢測FINS. ADP. FFA等指標(biāo),FPG測定采用葡萄糖氧化酶法,FINS. ADP. FFA測定采用ELISA法。取肝臟,使用蛋白印跡檢測手段,觀察針刺前后胰島素抵抗模型大鼠肝臟AMPK. ACC蛋白表達(dá)情況。使用透射電鏡觀察針刺后胰島素抵抗模型大鼠肝臟組織超微結(jié)構(gòu)形態(tài)學(xué)的改變。成果：1.高脂飼料飼養(yǎng)12周后,模型組、西藥組、電針組大鼠的GIR均較空白組顯著降低(P0.01),表明造模成功。經(jīng)過2周治療后,西藥組、電針組的GIR較模型組顯著升高(P0.01)。2.透射電鏡觀察：空白組干細(xì)胞中細(xì)胞器結(jié)構(gòu)完好,線粒體、粗面內(nèi)質(zhì)網(wǎng)豐富,胞漿內(nèi)無脂滴及脫顆�，F(xiàn)象,線粒體膜、嵴結(jié)構(gòu)完整,排列規(guī)則,粗面內(nèi)質(zhì)網(wǎng)排列整齊；模型組肝細(xì)胞內(nèi)可見大量脂滴分布,線粒體呈現(xiàn)不同程度腫脹,線粒體嵴變少變短,甚至出現(xiàn)空泡化。通過治療,西藥組、電針組肝細(xì)胞胞漿中脂滴較模型組減少,線粒體腫脹減輕,內(nèi)外膜部分融合。3.模型組血清中ADP較空白組顯著性降低(R0.01), FFA較空白組顯著性升高(P0.01)。經(jīng)治療后,西藥組、電針組的ADP較模型組顯著性升高(R0.01, R0.05), FFA較模型組顯著性降低(P0.01,P0.05)。4.模型組大鼠肝臟的AMPK蛋白水平較空白組顯著降低(P0.01), ACC蛋白水平顯著性升高(P0.05)。經(jīng)治療后,西藥組、電針組AMPK蛋白水平較模型組顯著升高(P0.01,P0.05)；西藥組、電針組ACC蛋白水平較模型組顯著降低(P0.01)。結(jié)論：研究表明,電針可通過激活脂聯(lián)素介導(dǎo)的信號通路,上調(diào)AMPK蛋白表達(dá),進(jìn)而下調(diào)ACC蛋白表達(dá),以調(diào)整機體脂質(zhì)代謝紊亂從而改善胰島素抵抗?fàn)顟B(tài)。這可能是針刺治療胰島素抵抗的機制之一。
[Abstract]:The first part of the literature study is a potential threat to developing countries and developed countries with the improvement of living standards, dietary patterns and human diet related diseases. The dietary habits of excess nutrition and the mode of sitting mainly lead to the frequent development of modern metabolic diseases. The most obvious is diabetes mellitus (DM). IR, as a precursor of diabetes, is highly concerned by modern research. And as a "common soil" for hypertension, fatty liver, polycystic ovary syndrome and other diseases, insulin resistance is widely concerned. The current research shows that the trend of diabetes incidence is increasing year by year, seriously endangering human health. So far, the pathogenesis of type 2 diabetes (T2DM) has not been completely dissect. Insulin resistance and insulin beta cell dysfunction are the basic characteristics of modern medicine. Obesity, hypertension, diabetes and insulin resistance are closely related to the excess nutrition in modern life. Insulin resistance is the core link in the occurrence of T2DM. The key to T2DM and insulin resistance related diseases is to adjust the abnormal insulin signaling pathway to improve insulin resistance, which is the key to the treatment of T2DM. Great contributions have been made to the medical cause of human being, with rich clinical experience, or by writing medical cases to share clinical experiences, or to carry out experimental deepening research. A large number of literatures show that acupuncture treatment of insulin resistance related diseases has an important potential in the process of insulin resistance, and its mechanism is closely related to the improvement of insulin resistance. Through previous studies, we found that acupuncture can improve insulin resistance through receptor and receptor level. In order to further improve the mechanism of acupuncture to improve insulin resistance, this topic chooses insulin resistance, the disorder of lipid metabolism in the development process as a breakthrough point, AMPK-ACC signal transduction pathway induced by adiponectin as a signal transduction pathway. Research direction, through the detection of relevant indicators to observe the theory of acupuncture on insulin resistance from macro to microcosmic, and further prove its mechanism and therapeutic effect. The second part of the experimental study: using high fat diet induced insulin resistance model rats as the research object, with the thiazolidane two ketone drug pioglitazone as the control, The effects of acupuncture on serum adiponectin, free fatty acid content, the expression of AMPK and ACC in the liver, and the changes in the ultrastructural morphology of the liver were observed. The effects of acupuncture on the lipid metabolism disorder of insulin resistance were explained at a multi-level and multilevel level, and a new theory was provided for the enhancement of the islet sensitive function. Methods: 52 male SPF grade SD rats (180-220g) common feed was fed for 5 days, 10 normal groups were randomly selected as normal diet, and the remaining rats were fed with high fat feed for 3 months. From the eighth week, all rats were taken blood from the orbital venous sinus every other week to detect the fasting blood glucose (FPG) and plasma Insulin (FINS), and the insulin sensitivity index (ISI, HOMA-IR), when the model group was significantly lower (P0.05) than the blank group (P0.05), HOMA-IR significantly increased (P0.05), that is, the high insulin positive glucose clamp test, when the glucose infusion rate (GIR) was significantly lower than the empty white group (P0.05) was a successful model. After twelfth weeks of successful model production, harvest Stratified random method was divided into 3 groups: model group (11), western medicine group (13), electroacupuncture group (12). The blank group continued to feed with ordinary feed for 2 weeks, the model group continued to feed with high fat feed for 2 weeks. The electroacupuncture Group continued to feed high fat feed for 2 weeks, and the acupuncture treatment was given, "Feng long", "Three Yin Jiao", and 1 times. For 2 weeks, pioglitazone suspension was given at the same time with 10mg/kg gavage, 1 times. The rats in each group were used to detect FINS. ADP. FFA in the orbital venous sinus after the end of the treatment. The FPG was measured by the glucose oxidase method and the FINS. ADP. FFA was measured by ELISA. The liver was taken and the insulin resistance was observed before and after the acupuncture. The expression of AMPK. ACC protein in the liver of the model rats was observed. The ultrastructural morphological changes of the liver tissues of the rats were observed by transmission electron microscope. Results: after 12 weeks of feeding of 1. high fat diet, the GIR of the rats in the model group, the western medicine group and the electroacupuncture group were significantly lower than those in the blank group (P0.01), indicating that the model was successful after 2 weeks of treatment. After that, the GIR in the western medicine group and the electroacupuncture group were significantly higher than the model group (P0.01).2. transmission electron microscope observation: the cell organelle structure in the blank group was intact, the mitochondria, the rough endoplasmic reticulum rich, the cytoplasm no fat drop and degranulation phenomenon, the mitochondria membrane, the ridge structure complete, the arrangement rules, the rough endoplasmic reticulum arranged neatly; the model group liver cells can be seen big inside. After treatment, the lipid droplets in the cytoplasm of liver cells in the western medicine group and electroacupuncture group decreased compared with the model group, the swelling of mitochondria decreased, and the serum ADP in the.3. model group was significantly lower than that in the blank group (R0.01), and the FFA was more significant than that in the blank group. After treatment, the ADP in the western medicine group and the electroacupuncture group was significantly higher than the model group (R0.01, R0.05), and the FFA in the model group was significantly lower than that in the model group (P0.01, P0.05). The level of AMPK protein in the liver of the rat liver was significantly lower than that in the blank group (P0.01), and the ACC protein was significantly increased (P0.05). After treatment, the western medicine group and the electroacupuncture group had a protein water. Compared with the model group (P0.01, P0.05), the level of ACC protein in the western medicine group and the electroacupuncture group was significantly lower than that in the model group (P0.01). Conclusion: the study showed that the electroacupuncture could increase the expression of AMPK protein by activating the signal pathway mediated by adiponectin, and then down the expression of ACC protein in order to adjust the disorder of lipid metabolism and improve the insulin resistance. This may be one of the mechanisms of acupuncture for insulin resistance.
【學(xué)位授予單位】：廣州中醫(yī)藥大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2016
【分類號】：R245

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