本文選題：針刺 + 胰島素抵抗��； 參考：《廣州中醫(yī)藥大學(xué)》2017年博士論文

【摘要】：本研究是以PI3K胰島素信號(hào)轉(zhuǎn)導(dǎo)途徑為基礎(chǔ),設(shè)計(jì)實(shí)驗(yàn)觀察針刺對(duì)胰島素抵抗(IR)的干預(yù)作用;以自發(fā)性胰島素抵抗模型-OLETF大鼠為動(dòng)物模型,用R燈-PCR、Western blotting等檢測(cè)方法,檢測(cè)指標(biāo)空腹血糖(FPG)、血漿胰島素(FINS)、C肽、腦脊液胰島素,以觀察針刺干預(yù)對(duì)OLETF大鼠海馬中IRS-2、PI3K、Akt、GSK的mRNA和蛋白表達(dá)的改變,以及大鼠海馬中Aβ的沉淀以及Tau蛋白mRNA改變的情況,由分子生物學(xué)水平探討針刺改善胰島素抵抗的機(jī)制原理。目的:以自發(fā)性胰島素抵抗模型OLETF大鼠為研究對(duì)象,在此動(dòng)物模型基礎(chǔ)上建立AD模型,觀察針刺(穴選百會(huì)、腎俞、內(nèi)關(guān)、足三里、三陰交)對(duì)AD模型大鼠中樞胰島素抵抗?fàn)顟B(tài)的影響,初步探討針刺對(duì)AD模型大鼠中樞胰島素信號(hào)轉(zhuǎn)導(dǎo)PI3K通路各組成蛋白(IRS-2,PI3K,Akt,IDE,GSK-3α/β,Aββ,Tau)表達(dá)的作用,從中樞胰島素信號(hào)轉(zhuǎn)導(dǎo)通路的角度闡釋針灸治療AD的機(jī)理。方法:選用自發(fā)性胰島素抵抗OLETF大鼠和同品系LETO大鼠,以O(shè)LETF大鼠為基礎(chǔ)建立AD模型。造模方法采用腹腔注射D-半乳糖和灌胃A1C13溶液的方法建立AD 模型。D-半乳糖采用 60mg · kg-1 · d-1,A1C13 采用 50mg · kg-1 · day-1,按照1Oml/kg溶液體積配置溶液。連續(xù)造模60天,造模完成后用Morris水迷宮進(jìn)行行為學(xué)測(cè)試,剔除不合格模型。以L(fǎng)ETO大鼠為正常組,將造模成功的OLETF大鼠隨機(jī)分為模型組和針刺組,每組8只。針刺組給予針刺干預(yù),穴選百會(huì)、腎俞(雙)、內(nèi)關(guān)(雙)、足三里(雙)、三陰交(雙),連續(xù)治療三周。治療結(jié)束后,檢測(cè)所有大鼠空腹血糖(FPG)、血漿胰島素(FINS)、血清C-肽(C-P),和海馬中的IRS-2、PI3K-p85α、Akt2、IDE、GSK-3α/β,以及海馬中的 Aβ 含量、tau 蛋白。結(jié)果:針刺干預(yù)的EA-AD-OLETF組大鼠的FPG、FINS、C-P較模型AD-OLETF組顯著降低(P0.01)。Morris水迷宮實(shí)驗(yàn)中,模型AD-OLETF組較正常LETO組穿越原平臺(tái)象限時(shí)間占總時(shí)間百分比減小(P0.01);針刺EA-AD-OLETF組較模型組則顯增大(P0.05)。海馬中的 IRS-2、PI3K-p85α、Akt2、IDE、GSK-3α/β 針刺作用后,其mRNA變化不明顯,但是其相關(guān)的p-IRS-2、IDE、p-GSK-3 β蛋白在干預(yù)后有了明顯的提升(P0.01,P0.05),p-PI3K-p85α、p-Akt2 蛋白較干預(yù)前有所降低(P0.05)。在針刺干預(yù)后,針刺組EA-AD-OLETF組大鼠海馬中Aβ沉淀細(xì)胞的個(gè)數(shù)較AD-OLETF組明顯減少(P0.05)。針刺干預(yù)后的EA-AD-OLETF大鼠海馬Tau mRNA表達(dá)比 AD-OLETF 升高(P0.05)。結(jié)論:從針刺干預(yù)胰島素抵抗角度治療AD,可以明顯改善模型大鼠胰島素抵抗?fàn)顟B(tài),并且改善其認(rèn)知行為,可以增加對(duì)A β的降解,改善A β在海馬的沉積,抑制Tau蛋白表達(dá)�？偨Y(jié)提出"針刺影響胰島素IRS-PI3K-Akt-GSK信號(hào)轉(zhuǎn)導(dǎo)途徑可能是針刺干預(yù)胰島素抵抗影響AD狀態(tài)的關(guān)鍵環(huán)節(jié)之一",為臨床運(yùn)用針刺治療胰島素抵抗提供新的科學(xué)證據(jù)和理論基礎(chǔ)。
[Abstract]:On the basis of PI3K insulin signal transduction pathway, we designed an experiment to observe the intervention effect of acupuncture on insulin resistance (IRR), and used spontaneous insulin resistance model (-OLETF) as animal model, using R-PCRX Western blotting, and so on. To observe the effect of acupuncture intervention on the expression of mRNA and protein in the hippocampus of OLETF rats, as well as the precipitation of A 尾 and the changes of Tau mRNA in hippocampus of OLETF rats. To explore the mechanism of acupuncture in improving insulin resistance from molecular biological level. Objective: to establish AD model on the basis of spontaneous insulin resistance (OLETF) model in rats and observe acupuncture (points Xanbaihui, Shenshu, Neiguan, Zusanli). The effect of acupuncture on the expression of GSK-3 偽 / 尾 A 尾 Tau3 in central insulin signal transduction PI3K pathway of AD model rats was studied in order to explore the effect of acupuncture on the expression of GSK-3 偽 / 尾 A 尾 Taug in the central insulin signal transduction pathway of AD rats, and the expression of GSK-3 偽 / 尾 A 尾 Taug in the central insulin signal transduction pathway of AD model rats. To explain the mechanism of acupuncture and moxibustion in treating AD from the angle of central insulin signal transduction pathway. Methods: the AD model of spontaneous insulin resistance (OLETF) rats and homologous LETO rats was established on the basis of OLETF rats. The AD model was established by intraperitoneal injection of D-galactose and intragastric administration of A1C13 solution. 60mg kg-1 d-1A1C13 was used for 50mg kg-1 day-1, and the solution was configured according to the volume of 1Oml/kg solution. After 60 consecutive days of modeling, Morris water labyrinth was used to conduct behavioral tests to eliminate the unqualified model. LETO rats were randomly divided into model group and acupuncture group with 8 rats in each group. Acupuncture group was given acupuncture intervention, point selection Baihui, Shenshu (Shuangzheng, Neiguan (Shuangzhu, Zusanli), Sanyinjiao (Shuangzhuo, Shuangjingjiao), continuous treatment for three weeks. At the end of treatment, fasting blood glucose (FPG), plasma insulin (FINSN), serum C- peptide (C- peptide) and PI3K-p85 偽 in hippocampus (IRS-2PI3K-p85 偽), GSK-3 偽 / 尾, and A 尾 content in hippocampus were measured in all rats. Results: compared with the model AD-OLETF group, the time of crossing the original platform quadrant in the model AD-OLETF group was significantly lower than that in the normal LETO group, and that in the acupuncture EA-AD-OLETF group was significantly higher than that in the model group. Results: compared with the model AD-OLETF group, the percentage of the total time of crossing the original platform quadrant in the model AD-OLETF group was significantly lower than that in the model AD-OLETF group, and that in the acupuncture EA-AD-OLETF group was significantly higher than that in the model group. The mRNA of IRS-2PI3K-p85 偽 and Akt2I3K-p85 偽 after acupuncture did not change significantly, but the related protein of p-IRS-2IDEP-GSK-3 尾 increased significantly after intervention, and the protein of p-PI3K-p85 偽 -p-Akt2 was lower than that of P0.05p85 偽 -PI3K-p85 偽. After acupuncture intervention, the number of A 尾 -precipitated cells in hippocampus of EA-AD-OLETF group was significantly lower than that of AD-OLETF group. The expression of Tau mRNA in hippocampus of EA-AD-OLETF rats after acupuncture intervention was higher than that of AD-OLETF. Conclusion: the treatment with acupuncture on insulin resistance can obviously improve the insulin resistance state and cognitive behavior of the model rats, increase the degradation of A 尾, improve the deposition of A 尾 in the hippocampus and inhibit the expression of Tau protein. It is concluded that "acupuncture affecting insulin IRS-PI3K-Akt-GSK signal transduction pathway may be one of the key links of acupuncture intervention in insulin resistance affecting AD state", which provides a new scientific evidence and theoretical basis for clinical treatment of insulin resistance.
【學(xué)位授予單位】：廣州中醫(yī)藥大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：R245;R-332

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