本文選題：電針 + 2型糖尿病��； 參考：《北京中醫(yī)藥大學(xué)》2017年博士論文

【摘要】：背景:2型糖尿病(T2DM)發(fā)病率、死亡率、經(jīng)濟(jì)消耗均較高,給社會和家庭帶來了沉重的負(fù)擔(dān)。既往關(guān)于T2DM的研究多重視胰島素抵抗,口服藥物也主要以胰島素增敏劑和促胰島素分泌劑為主。而在T2DM的發(fā)生、發(fā)展過程中β細(xì)胞功能失調(diào)和細(xì)胞凋亡起著至關(guān)重要的作用,目前尚沒有藥物能抑制β細(xì)胞凋亡和功能衰竭。而抑制MST1可能就是改善β細(xì)胞功能失調(diào)、抑制β細(xì)胞凋亡從而治療T2DM的新靶點(diǎn)。臨床及實(shí)驗(yàn)研究均證明針灸可有效干預(yù)T2DM。胰俞(胃脘下俞)、脾俞、腎俞是針灸治療T2DM的常用穴,且三穴均位于胰腺同神經(jīng)節(jié)段。本研究以此為出發(fā)點(diǎn)設(shè)計(jì)實(shí)驗(yàn),觀察電針"胰俞"、"脾俞"、"腎俞"干預(yù)T2DM動物模型,是否存在療效差異,并探索電針三背俞穴是否通過MST1相關(guān)通路影響β細(xì)胞功能和凋亡。本實(shí)驗(yàn)聚焦于β細(xì)胞功能和β細(xì)胞凋亡,吸引大家對于其在T2DM發(fā)生發(fā)展中作用的重視;同時(shí)也更能體現(xiàn)出針灸相較于現(xiàn)有藥物通過多途徑干預(yù)T2DM的優(yōu)勢;MST1是調(diào)節(jié)β細(xì)胞功能和凋亡的多途徑通路的上游指標(biāo),將研究聚焦于MST1,為針灸干預(yù)T2DM的研究提出新的著眼點(diǎn),同時(shí)可從更宏觀角度對針刺改善T2DM進(jìn)行探究。此外,驗(yàn)證了針刺對于MST1的良性調(diào)節(jié),可推動針刺對于T1DM療效和干預(yù)機(jī)制的研究,從而擴(kuò)大針灸的應(yīng)用范圍。目的:1.通過檢測電針"胰俞"、"脾俞"、"腎俞"對T2DM模型大鼠體質(zhì)量、空腹血糖(FBG)、口服葡萄糖耐量試驗(yàn)(OGTT)、糖化血清蛋白(GSP)、血脂、空腹胰島素(FINS)、胰島素抵抗指數(shù)(HOMA-IR)、胰島β細(xì)胞形態(tài)的影響,觀察電針"胰俞"、"脾俞"、"腎俞"對T2DM的干預(yù)效果及療效差異。2.通過檢測電針"胰俞"、"脾俞"、"腎俞"對T2DM模型大鼠胰島β細(xì)胞中MST1基因及蛋白表達(dá)、MST1裂解蛋白(clMST1)和磷酸化蛋白(pMST1)、BIM和caspase-3活化、PDX-1蛋白、INS基因和蛋白表達(dá)的影響,觀察電針"胰俞"、"脾俞"、"腎俞"對T2DM模型大鼠胰島β細(xì)胞凋亡和合成INS功能的影響,探究電針"胰俞"、"脾俞"、"腎俞"干預(yù)T2DM的作用機(jī)制及差異。方法:將48只雄性SD大鼠隨機(jī)分為正常組8只和2型糖尿病造模組(簡稱"造模組")40只。造模組高糖高脂飼料喂養(yǎng)50天的基礎(chǔ)上以35mg/kg.BW腹腔注射新鮮配制的鏈脲佐菌素(STZ)溶液以制造2型糖尿病模型。注射后72h尾靜脈采血,以羅氏血糖儀檢測隨機(jī)血糖;注射STZ2周后對大鼠行OGTT。以隨機(jī)血糖≥16.7mmol/L,OGTT2h后血糖≥11.1mmol/L的大鼠為成功造模大鼠,納入后續(xù)試驗(yàn)。造模成功32只,根據(jù)血糖水平隨機(jī)區(qū)組分組,分為模型組8只,電針胰俞組8只,電針脾俞組8只,電針腎俞組8只。各電針組每日干預(yù)1次,每次20min,6次/周,連續(xù)干預(yù)4周。每日觀察記錄大鼠的一般狀況;每周末檢測各組大鼠體質(zhì)量和FBG;干預(yù)前后進(jìn)行OGTT試驗(yàn),計(jì)算曲線下面積。4周后麻醉處死,腹主動脈取血,離心取血清,以自動生化分析儀檢測血清甘油三酯(TG)、總膽固醇(TC)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)、GSP水平,以放免法檢測血清INS水平。取部分胰腺組織,一部分多聚甲醛固定,以HE染色觀察胰島形態(tài),并以免疫組化方法檢測胰島β細(xì)胞中MST1、clMST1、pMST1、BIM、caspase-3活化、PDX1、INS蛋白的表達(dá)水平;一部分液氮凍存,以Real-time PCR法檢測大鼠胰腺組織中目的基因MST1及INS的表達(dá)水平。結(jié)果:1.血糖代謝相關(guān)指標(biāo):本實(shí)驗(yàn)結(jié)果顯示:在干預(yù)4周期間,模型組大鼠體質(zhì)量基本呈下降態(tài)勢,4周后較干預(yù)前明顯降低;而FBG一直維持在較高水平,4周后較干預(yù)前顯著升高;GSP水平也顯示其在過去2-3周內(nèi)血糖維持在較正常組明顯升高的狀態(tài);OGTT結(jié)果顯示其在干預(yù)前后均較正常組葡萄糖耐量顯著受損,且干預(yù)4周后OGTT曲線下面積較自身干預(yù)前顯著升高,與FBG變化趨勢一致;干預(yù)4周后HOMA-IR也顯著高于正常組;總體而言,說明了干預(yù)期4周后模型組大鼠血糖升高,葡萄糖耐量受損和胰島素抵抗情況惡化,T2DM有所進(jìn)展。而電針胰俞組大鼠,在4周干預(yù)期間,體質(zhì)量變化趨勢同模型組一致,同時(shí)間點(diǎn)比較均沒有顯著差異;FBG較自身而言,在干預(yù)第1周末有顯著下降,但在干預(yù)第2周末又有所回升,此后一直維持在較高水平;但與同時(shí)期模型組相比,電針胰俞組在干預(yù)第3、4周末FBG水平顯著下降;GSP水平也顯示其在過去2-3周內(nèi)血糖平均水平較模型組是顯著下降的;OGTT結(jié)果同F(xiàn)BG變化趨勢一樣,干預(yù)前后自身無明顯變化,但在干預(yù)4周后曲線下面積顯著低于模型組;干預(yù)4周后,電針胰俞組HOMA-IR較模型組顯著下降;總體而言,電針胰俞穴干預(yù)T2DM模型大鼠4周,可顯著抑制血糖升高,改善葡萄糖耐量受損和胰島素抵抗?fàn)顟B(tài)的惡化,抑制T2DM的發(fā)展。電針脾俞組大鼠,在4周干預(yù)期間,體質(zhì)量變化趨勢同模型組、電針胰俞組一致,同時(shí)間點(diǎn)比較均沒有顯著差異;FBG較自身而言,在干預(yù)第1、2周末較干預(yù)前顯著下降,但干預(yù)第3、4周又顯著回升;與同時(shí)期模型組相比,干預(yù)每周末血糖水平均有下降,但差異不顯著;GSP水平顯示其在過去2-3周內(nèi)血糖平均水平較模型組是顯著下降的;OGTT結(jié)果同F(xiàn)BG變化趨勢一樣,干預(yù)前后自身無明顯變化,干預(yù)4周后曲線下面積比模型組有所縮減,但差異不顯著;干預(yù)4周后,電針脾俞組HOMA-IR較模型組顯著下降;總體而言,電針脾俞穴干預(yù)T2DM模型大鼠4周,還是可以改善大鼠血糖升高和葡萄糖耐量受損、胰島素抵抗?fàn)顟B(tài)惡化趨勢的,只是不如電針胰俞穴顯著。電針腎俞組大鼠,在4周干預(yù)期間,體質(zhì)量變化趨勢同模型組、電針胰俞組及電針脾俞組一致,同時(shí)間點(diǎn)比較均沒有顯著差異;FBG較自身而言,在干預(yù)第1周末有顯著下降,但在干預(yù)第2周末又有所回升,此后一直維持在較高水平;與同時(shí)期模型組相比,電針腎俞組在干預(yù)第3、4周末FBG水平下降,但差異不顯著;其在第2周末的FBG水平顯著高于電針脾俞組,說明在第2周末時(shí)電針脾俞穴降血糖作用優(yōu)于電針腎俞穴;GSP水平顯示其在過去2-3周內(nèi)血糖平均水平也較模型組是顯著下降的;OGTT結(jié)果同F(xiàn)BG變化趨勢一樣,干預(yù)前后自身無明顯變化,干預(yù)4周后曲線下面積比模型組有所縮減,但差異不顯著;干預(yù)4周后,電針腎俞組HOMA-IR較模型組顯著下降;總體而言,電針腎俞穴干預(yù)T2DM模型大鼠4周,同電針脾俞穴相似,還是可以改善大鼠血糖升高和葡萄糖耐量受損、胰島素抵抗?fàn)顟B(tài)惡化趨勢的,只是不如電針胰俞穴顯著。2.血脂相關(guān)指標(biāo):本實(shí)驗(yàn)結(jié)果顯示:T2DM模型組大鼠TC、TG、LDL水平均較正常組大鼠顯著升高,而HDL水平與正常組大鼠無明顯變化。這符合HFD/STZ造模大鼠的血脂代謝紊亂特點(diǎn)。電針胰俞穴干預(yù)T2DM模型大鼠4周,可降低其TC、TG和LDL水平,改善脂質(zhì)代謝。電針脾俞穴干預(yù)T2DM模型大鼠4周,可降低其LDL水平,而對TC、TG、HDL水平無顯著影響。電針腎俞穴干預(yù)T2DM模型大鼠4周,可降低TC和LDL水平,而對TG、HDL水平無顯著影響。電針胰俞穴調(diào)節(jié)TG的能力優(yōu)于電針脾俞穴;電針胰俞調(diào)節(jié)血脂紊亂的能力比電針脾俞穴和電針腎俞穴更為顯著;這也可能是電針胰俞穴調(diào)節(jié)血糖作用比電針脾俞穴和電針腎俞穴更為顯著的原因之一。3.胰島素水平:本實(shí)驗(yàn)結(jié)果顯示:模型組大鼠胰島素水平與正常組無顯著差異,而電針胰俞穴可顯著降低T2DM模型大鼠胰島素水平,電針脾俞穴、電針腎俞穴有降低胰島素水平的趨勢,但效果不顯著。4.MST1相關(guān)機(jī)制指標(biāo):本實(shí)驗(yàn)結(jié)果顯示:與正常組相比,T2DM模型組大鼠MST1基因和蛋白的表達(dá)增多,MST1蛋白的裂解和磷酸化水平升高,即MST1蛋白的活化增多;線粒體凋亡途徑中促凋亡因子BIM蛋白和caspase-3裂解蛋白表達(dá)增多,即BIM和caspase-3的活化增強(qiáng),細(xì)胞凋亡增多;PDX1蛋白的表達(dá)減少,INS基因和蛋白表達(dá)減少,即胰島β細(xì)胞合成胰島素的功能降低。電針胰俞穴、電針脾俞穴均可減少T2DM模型大鼠MST1基因和蛋白的表達(dá),并顯著抑制MST1蛋白的裂解和磷酸化,即抑制MST1蛋白的活化;從而進(jìn)一步顯著抑制線粒體凋亡途徑中促凋亡因子BIM和caspase-3的活化,產(chǎn)生抑制細(xì)胞凋亡的效應(yīng)。同時(shí)電針胰俞穴、電針脾俞穴均可顯著促進(jìn)PDX1蛋白的表達(dá),并促進(jìn)PDX1啟動INS基因的轉(zhuǎn)錄表達(dá),促進(jìn)INS蛋白的表達(dá),即促進(jìn)胰島β細(xì)胞合成胰島素的功能。而電針腎俞穴可抑制MST1基因和蛋白的表達(dá),并顯著抑制MST1蛋白的裂解,對其磷酸化的影響效果不明顯;但也可以進(jìn)一步顯著抑制BIM和caspase-3的活化,產(chǎn)生抑制細(xì)胞凋亡的效應(yīng)。同時(shí)電針腎俞穴可顯著促進(jìn)PDX1蛋白的表達(dá),但對于INS基因轉(zhuǎn)錄的影響不明顯,卻可以顯著促進(jìn)INS蛋白的表達(dá),由此也可說電針腎俞穴亦可以促進(jìn)胰島β細(xì)胞合成胰島素的功能。由此可見,電針胰俞穴、電針脾俞穴、電針腎俞穴均可以通過調(diào)節(jié)MST1相關(guān)基因和蛋白表達(dá)抑制β細(xì)胞的凋亡,促進(jìn)β細(xì)胞合成胰島素的功能。結(jié)論:1.電針胰俞穴、電針脾俞穴、電針腎俞穴干預(yù)T2DM模型大鼠4周,均可以抑制T2DM大鼠血糖升高、葡萄糖耐量受損、胰島素抵抗?fàn)顟B(tài)惡化的趨勢,均可從一定程度上改善血脂代謝;但電針脾俞穴和電針腎俞穴調(diào)節(jié)血糖、血脂代謝的能力不如電針胰俞穴顯著。由此可見,胰俞在干預(yù)治療T2DM上具有一定的優(yōu)勢和特異性。鑒于三穴均位于胰腺同神經(jīng)節(jié)段內(nèi),但又與胰腺有不同節(jié)段聯(lián)系,還不能確定電針胰俞、脾俞、腎俞干預(yù)T2DM起效的機(jī)制及療效的差異與神經(jīng)節(jié)段無關(guān),但具體關(guān)系還有待進(jìn)一步的探究。2.電針胰俞穴、電針脾俞穴、電針腎俞穴干預(yù)T2DM模型大鼠4周,均可通過抑制MST1基因和蛋白的表達(dá),以及抑制MST1的活化,抑制β細(xì)胞凋亡,促進(jìn)β細(xì)胞合成INS能力,進(jìn)而發(fā)揮調(diào)節(jié)血糖、血脂代謝的作用。電針胰俞穴、電針脾俞穴、電針腎俞穴對機(jī)制指標(biāo)影響無明顯差異。胰俞干預(yù)T2DM的特異性機(jī)制還有待進(jìn)一步探索。
[Abstract]:Background: the incidence, mortality and economic consumption of type 2 diabetes mellitus (T2DM) are all high, bringing heavy burden to society and family. Previous studies on T2DM pay more attention to insulin resistance. Oral drugs are mainly insulin sensitizer and insulin secretant. In the development of T2DM, the development process of beta cell dysfunction and cells Apoptosis plays a vital role. At present, there is no drug to inhibit apoptosis and failure of beta cells. Inhibition of MST1 may be a new target for the improvement of beta cell dysfunction, inhibition of beta cell apoptosis and the treatment of T2DM. Clinical and experimental studies have proved that acupuncture can effectively interfere with T2DM. Yishu (xiishu), spleen Yu, and Shenshu is the treatment of acupuncture and moxibustion. The common acupoints for the treatment of T2DM were located in the same ganglion segment of the pancreas. This study was designed as the starting point for the experiment to observe the effect of Electroacupuncture on "Yishu", "spleen Yu" and "Shenshu" in the T2DM animal model, whether there was a difference in effect and whether the three back Shu Points of electroacupuncture could affect the function and apoptosis of beta cells through the MST1 related pathway. The experiment focused on the beta cells. Function and beta cell apoptosis attract people's attention to its role in the development of T2DM; meanwhile, it can also reflect the advantages of acupuncture and moxibustion compared with existing drugs to intervene in T2DM through multiple pathways; MST1 is the upstream index for regulating the function and apoptosis of beta cells, focusing on MST1, and putting forward a new study on the intervention of acupuncture and moxibustion in T2DM. At the same time, we can explore the improvement of T2DM by acupuncture at a more macro point of view. Furthermore, it proves that acupuncture has a good regulation of MST1, which can promote the effect of acupuncture on the effect of T1DM and the mechanism of intervention, so as to enlarge the application scope of acupuncture and moxibustion. Objective: 1. the body mass of T2DM model rats was detected by the detection of electroacupuncture "Yu Yu", "spleen Yu" and "Shenshu". Blood glucose (FBG), oral glucose tolerance test (OGTT), glycosylated serum protein (GSP), blood lipid, fasting insulin (FINS), insulin resistance index (HOMA-IR), the morphology of islet beta cells, observation of the effect and effect difference of Electroacupuncture of "Yu Yu", "spleen Yu", "Shenshu" on T2DM and the difference of curative effect.2. through the detection of electroacupuncture "Yu Yu", "spleen Yu", "Shenshu" "T2DM model big. The effects of MST1 gene and protein expression, MST1 lysis protein (clMST1) and phosphorylated protein (pMST1), BIM and caspase-3 activation, PDX-1 protein, INS gene and protein expression, and the effect of Electroacupuncture on the apoptosis of pancreatic beta cells and the function of INS in T2DM model rats were observed, and the Electroacupuncture of "Yu Yu" and "spleen Yu" were investigated. The mechanism and difference of the effect of "Shenshu" on the intervention of T2DM. Methods: 48 male SD rats were randomly divided into 8 rats in the normal group and 40 in type 2 diabetes model ("model group"). On the basis of high sugar and high fat feed for 50 days, a new type of streptozotocin (STZ) solution was injected into 35mg/kg.BW to produce type 2 diabetes model. After 72h tail vein blood sampling, random blood sugar was detected by Roche blood glucose meter. Rats with OGTT. with random blood glucose of more than 16.7mmol/L and OGTT2h after OGTT2h after STZ2 weeks were successful model rats, and the model group was successfully established. The model group was divided into 8 rats in the model group and 8 rats in the electroacupuncture and the Yu group. Acupuncture and spleen Yu Group 8, electroacupuncture Shenshu Group 8. Each acupuncture group intervention 1 times a day, each time 20min, 6 times per week, continuous intervention for 4 weeks. Observe and record the general condition of rats daily; test each group of rats' body mass and FBG every weekend; before and after the intervention, the OGTT test, the calculation of the area under the curve for.4 weeks after anesthesia, the abdominal aorta blood, centrifugation serum, in order to take the serum, in order to centrifuge the serum. Serum triglyceride (TG), total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL), GSP level, serum INS level were detected by radioimmunoassay analyzer. Partial pancreatic tissue, partial paraformaldehyde was fixed, HE staining was used to observe the form of islet, and MST1, clMST1, pMST in islet beta cells were detected by immunohistochemical method. 1, BIM, caspase-3 activation, PDX1, INS protein expression level; a part of liquid nitrogen cryopreservation, Real-time PCR method to detect the expression level of MST1 and INS in rat pancreas tissue. Results: 1. blood glucose metabolism related indicators: the results of this experiment showed that during the 4 week intervention, the body mass of the model group decreased basically, 4 weeks later than before the intervention. The level of FBG maintained at a higher level and increased significantly after 4 weeks than before the intervention; the GSP level also showed that the blood glucose level in the last 2-3 weeks was significantly higher than that in the normal group; the OGTT results showed that the glucose tolerance was significantly impaired before and after the intervention, and the area under the OGTT curve was more than before the intervention for 4 weeks. In 4 weeks, HOMA-IR was significantly higher than that in the normal group, and after 4 weeks of intervention, HOMA-IR was also significantly higher than that of the normal group. In general, it was indicated that the blood glucose of the rats in the model group, the impaired glucose tolerance and the deterioration of insulin resistance, and the progress of T2DM in the model group after the dry expectation, and the body mass change during the 4 week intervention of the electroacupuncture and pancreas Yu group were the same as that of the model group. There was no significant difference at the same time point; FBG was significantly lower at the first weekend than the intervention, but it rose again at the end of the second week, and then maintained at a higher level, but compared with the same period model group, the level of FBG decreased significantly at the end of the intervention on the weekend of 3,4; the GSP level also showed that it was in the past 2-3 weeks. The average blood sugar level was significantly lower than that in the model group; the OGTT result was the same as the FBG change trend, but the area under the curve was significantly lower than that in the model group after 4 weeks of intervention, and after the intervention for 4 weeks, the HOMA-IR of the electroacupuncture and pancreas Yu group was significantly lower than that of the model group. In general, the electroacupuncture and Yishu acupoint intervention for the T2DM model rats was significant for 4 weeks. Inhibit the increase of blood glucose, improve the deterioration of glucose tolerance and insulin resistance, and inhibit the development of T2DM. The body mass changes during the 4 week intervention were the same as that in the model group, the electroacupuncture and the Yishu group, and there was no significant difference at the same time point; FBG was significantly lower than the intervention at the end of the intervention for the week 1,2. In the same period, the average blood glucose water decreased, but the difference was not significant compared with the same period model group, but the GSP level showed that the blood glucose level in the last 2-3 weeks was significantly lower than that in the model group; the OGTT result was the same with the FBG, and there was no obvious change before and after the intervention, and the curve after the intervention was 4 weeks after the intervention. The lower area was less than that of the model group, but the difference was not significant. After 4 weeks of intervention, the HOMA-IR was significantly lower than that of the model group. As a whole, the intervention of the T2DM model rats by the acupuncture at the acupuncture point of the spleen and the spleen can improve the increase of blood glucose and glucose tolerance in rats, and the tendency of insulin resistance to deteriorate is not as good as that of the electroacupuncture Yu Xuexian. In the 4 week intervention, the trend of body mass change was the same as that of the model group, the Electroacupuncture of the Yu Yu group and the electroacupuncture spleen Yu group, and there was no significant difference at the same time point. FBG compared with itself, there was a significant decrease at the end of the intervention for the first weekend, but after the intervention of the second weekend, it remained at a higher level; and the same period. Compared with the model group, the level of FBG in the electroacupuncture Shenshu group decreased at the end of the 3,4 weekend, but the difference was not significant. The level of FBG in the second weekend was significantly higher than that of the electroacupuncture spleen Yu group. It showed that the hypoglycemic effect of the acupuncture point at the second weekend was better than that of the electroacupuncture on the Shenshu Point. The level of GSP showed that the average level of blood glucose in the past 2-3 weeks was significantly lower than that of the model group. The OGTT results were the same as the FBG change trend, and there was no obvious change before and after intervention. After 4 weeks, the area under the curve was reduced, but the difference was not significant. After 4 weeks, the HOMA-IR of the electroacupuncture Shenshu group was significantly lower than that of the model group; in general, the electroacupuncture Shenshu acupoint was similar to the Electroacupuncture of the splenic Shu point for 4 weeks. In order to improve the increase of blood glucose and impaired glucose tolerance in rats, the tendency of insulin resistance to deteriorate is not as good as the significant.2..2. blood lipid related indexes of electroacupuncture and pancreas: the results of this experiment show that the level of TC, TG and LDL in the T2DM model group is significantly higher than that of the normal group, but the HDL level has no obvious change with the normal group. This conforms to the HFD/STZ made. The intervention of T2DM model rats with electroacupuncture at 4 weeks can reduce the level of TC, TG and LDL and improve the lipid metabolism. The interference of the T2DM model rats by the acupuncture of the electroacupuncture spleen Yu point for 4 weeks can reduce the level of LDL, but has no significant influence on the level of TC, TG and HDL. The intervention of the Shenshu Point in the T2DM model rats for 4 weeks can reduce TC and LDL levels. There was no significant influence on the level of TG and HDL. The ability of electroacupuncture at Yishu point to regulate TG was better than that of the Electroacupuncture of spleen Yu Xue, and the ability of electroacupuncture and pancreas Yu to regulate blood lipid disorders was more significant than that of the acupuncture point of the electroacupuncture spleen and the electroacupuncture of Shenshu. It may also be one of the more significant reasons for the regulation of blood glucose in the Electroacupuncture of the pancreas and the pancreas, which is one of the more significant reasons for the.3. insulin water than the electroacupuncture at the spleen and the electroacupuncture at the Shenshu Point. The results of this experiment showed that the insulin level in the model group was not significantly different from that in the normal group, but the electroacupuncture and pancreatic Yu Xueke significantly reduced the insulin level in the T2DM model rats, the electroacupuncture at the spleen Yu point and the electroacupuncture at Shenshu Point had a tendency to reduce the insulin level, but the effect was not significant in.4.MST1 phase. The results of this experiment showed that compared with the normal group, the results of this experiment showed that the results of this experiment were compared with that of the normal group. The expression of MST1 gene and protein in the T2DM model group increased, the MST1 protein lysis and phosphorylation level increased, that is, the activation of MST1 protein increased, the apoptosis factor BIM protein and the caspase-3 lysis protein expression increased in mitochondrial apoptosis pathway, that is, the activation of BIM and Caspase-3, the increase of apoptosis, the decrease of PDX1 protein, INS based The decrease of the protein expression and the decrease in the expression of insulin in islet beta cells. The electroacupuncture at the Yishu point and the Electroacupuncture of spleen Yu Xue can reduce the expression of MST1 gene and protein in the T2DM model rats, and significantly inhibit the cracking and phosphorylation of MST1 protein, that is, to inhibit the activation of MST1 protein, and thus further inhibit the apoptosis in mitochondrial apoptosis pathway to further inhibit apoptosis. The activation of factor BIM and caspase-3 produced the effect of inhibiting apoptosis. At the same time, electroacupuncture at Yishu point can promote the expression of PDX1 protein, promote the transcription of INS gene and promote the expression of INS protein, promote the function of islet beta cells in the islet beta cell synthesis, and the electroacupuncture at Shenshu point can inhibit the MST1 gene and the function of the MST1 gene and the electroacupuncture at Shenshu Point. Protein expression, and significantly inhibit the fragmentation of MST1 protein, has no obvious effect on its phosphorylation, but it can further inhibit the activation of BIM and Caspase-3 and inhibit the apoptosis of cells. At the same time, the electroacupuncture at Shenshu Point can significantly promote the expression of PDX1 protein, but the effect on INS gene transcription is not obvious, but it can be significant. The expression of INS protein can be promoted, and it can also be said that electroacupuncture at Shenshu Point can also promote the function of insulin synthesis in islet beta cells. Thus, it can be seen that electroacupuncture at Yishu acupoint, electroacupuncture spleen Yu point, and electroacupuncture at Shenshu Point can inhibit the apoptosis of beta cells by regulating MST1 related genes and protein expression, and promote the function of insulin synthesis in beta cells. Conclusion: 1. electroacupuncture. Yishu acupoint, electroacupuncture spleen Shu point, electroacupuncture at Shenshu Point intervention T2DM model rats for 4 weeks, can inhibit the increase of blood glucose in T2DM rats, the impaired glucose tolerance and the deterioration of insulin resistance, which can improve blood lipid metabolism to a certain extent, but the ability of electroacupuncture at spleen Yu point and Electroacupuncture at Shenshu acupoint to regulate blood glucose and blood lipid metabolism is not as good as that of electroacupuncture Yu Xue It can be seen that Yishu has some advantages and specificity in the intervention treatment of T2DM. Given that three points are all located in the same ganglion segment of the pancreas, but there are different segments associated with the pancreas, the mechanism and the difference of the effect of the intervention of T2DM in the electroacupuncture, the spleen Yu, the Shenshu intervention are not related to the ganglion segment, but the specific relationship remains to be entered. One step to explore.2. electroacupuncture at Yishu point, electroacupuncture spleen Yu point, electroacupuncture at Shenshu Point intervention T2DM model rats for 4 weeks, can inhibit the expression of MST1 gene and protein, and inhibit the activation of MST1, inhibit the apoptosis of beta cells, promote the synthesis of INS in beta cells, and then play the role of regulating blood glucose and lipid metabolism. Electroacupuncture at Yishu point, electric acupuncture spleen Yu Xue, electricity There is no significant difference in the effect of acupuncture Shenshu Point on the mechanism index. The specific mechanism of Yishu intervention on T2DM needs further exploration.

【學(xué)位授予單位】：北京中醫(yī)藥大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2017
【分類號】：R245

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