针刺逆转胰岛素抵抗血管内皮功能障碍的实验研究
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摘要
内皮功能障碍(Endothelium Dysfunction,ED)作为动脉粥样硬化(Artherosclerosis,AS)的始动环节,对疾病的发生发展有重大影响。近年发现胰岛素抵抗(IR)可导致内皮功能障碍,参与动脉粥样硬化的发病。胰岛素抵抗是代谢综合征多种疾病包括萄葡糖耐量异常、2型糖尿病、肥胖、血脂异常和高血压等代谢紊乱的基础,是动脉粥样硬化、冠状动脉粥样硬化性心脏病等多种心脑血管终点事件基础疾病的重要原因。其对血管的影响,最主要的是慢性并发症。目前血管病变的基础研究的热点话题为“血管内皮功能的障碍”是所有血管病变的中心环节。血管内皮功能的损伤是血管病变的起始环节,也是中心环节。目前,保护血管内皮,逆转内皮损害是防治血管病变的中心环节,也是目前现代医学仍无法突破的瓶颈问题。
针灸作为一种自然疗法,因其简、便、验、廉等优势在几千年的中医传统诊疗中起着十分重要的作用,且众多的研究也证实针灸具有良好的调节内分泌代谢的作用,在治疗诸多现代疾病中已逐渐显示出优势。虽然目前针刺治疗胰岛素抵抗等研究工作开展得较少,但针刺对糖尿病、肥胖、脑梗塞等相关疾病的疗效早已得到了国内外同行的公认。
前人的临床及实验研究表明,针刺对胰岛素抵抗具有一定的逆转效应——通过针刺干预可改善动物模型及糖尿病患者的胰岛素抵抗状态,并可防治慢性并发症的产生与发展,降低由于长期高血糖状态引发的血管性慢性并发症的产生。但目前研究对于以上作用的机制并未进行系统并有针对性的研究。
本研究是前人研究的基础上,以高糖、高脂、高盐饮食复制胰岛素抵抗动物实验模型,结合现代检测技术,深入探讨胰岛素抵抗状态下血管内皮功能的变化状况及针刺对内皮功能变化的影响作用。
全文分文献研究、实验研究和小结三大部分进行。
1文献研究
通过对大量关于胰岛素抵抗的文献综合研究,从胰岛素抵抗概念、胰岛素抵抗与相关疾病关系、胰岛素抵抗发生的影响因素以及胰岛素抵抗发生机理及防治等多方面阐述了胰岛素抵抗的最新研究进展,并对中医药防治胰岛素抵抗的研究现状进行了分析,特别对针灸治疗胰岛素抵抗的国内外研究进展进行了评述,提出今后的研究方向,认为针刺不失为改善胰岛素抵抗的有效方法之一,应加强对其作用机理的深入研究和探讨。
2实验研究
2.1方法
(1)实验分组
将60只雄性sD大鼠[体重(200±20)g以普通饲料进行适应性饲养1周,按体质量随机分为5组,每组12只,分别为空白对照组(Blank Group)、模型1组(ModelGroup 1)、模型2组(Model Group 2)、针刺1组(Acupuncture Therapy Group 1,AT1)和针刺2组(Acupuncture Therapy Group 2,AT2)。空白对照组以普通饲料喂养,其它各组均以高脂高糖高盐饲料饲养。从第5周开始至实验结束,每周测1次体重;从第4周开始,每隔1周空白对照组和模型1组大鼠从眼眶静脉窦采血1次,检测FPG、INS,并计算ISI进行对比,确定造模是否成功。第8周造模成功后,空白对照组、模型2组及针刺2组继续以普通饲料喂养4周,其中针刺2组同时给予针刺治疗,1次/d,连续4周;模型1组、针刺1组继续以高脂高糖高盐饲料喂养4周,其中针刺1组同时给予针刺治疗,1次/d,连续4周。
(2)取穴及针刺方法
取穴:穴位选用“脂三针”(手厥阴心包经“内关”、足阳明胃经“足三里”、足太阴脾经“三阴交”)以及足太阳膀胱经“肾俞”穴。其定位参照大鼠的常用针灸穴位:“内关”位于前肢内侧,离腕关节约3mm左右的尺挠骨缝间;“足三里”位于大鼠后肢膝关节外下方当排骨小头下约5mm处;“三阴交”位于大鼠后肢内踝尖直上10mm处;“肾俞”位于大鼠后背第二腰椎下旁开5mm之两旁肋间。
刺法:内关、足三里、三阴交均以30号1寸毫针(华佗牌,苏州医疗用品厂生产),沿皮斜刺8mm,针尖朝向肢体近端,肾俞直刺5mm,在内关、足三里穴,接电针治疗,将针柄分别连接至电针仪的电极上,采用青岛华声仪器厂生产的G6805电针仪,疏密波,频率5～10Hz强度以肌肉轻微抖为度,电压3～5v,时间持续30分钟。每天1次,连续治疗28天。
第12周实验结束后取标本进行相关指标的检测,结合免疫组学、病理、放射免疫检测等现代检测技术观察针刺对胰岛素抵抗大鼠模型、血脂、相关脏器(肝脏、胰腺)的形态学的影响,以及反应IR大鼠模型血管内皮功能的相关指标:血液流变学指标、相关细胞因子(TXB_2、6-Keto-PGF_(1α)、ET、NO)、主动脉VEGF表达的影响等的影响,重点突出针刺对IR大鼠模型血管内皮功能的影响。
2.2结果
2.2.1针刺对IR大鼠模型一般状况及体重的影响
实验过程中,正常对照组大鼠体质量逐渐增加,精神状态良好,反应灵敏,动作自如,毛发平伏有光泽,无1例死亡。第5周开始模型1、2组、针刺1组、针刺2组大鼠性情变温顺,体态肥胖,嗜睡少动,大鼠皮毛蓬乱而无光泽,大便量较正常组偏少,色灰,质较软,体重增长较快,腹部肥胖。一直以高脂、高糖、高盐饲料喂养的模型1组大鼠逐渐出现多饮、多食、多尿,且精神萎靡,反应迟钝,动作迟缓,后期体重增长缓慢,实验过程中死亡1只。模型2组在改用普通饲料喂养后(饮食干预),仅少数大鼠出现多饮、多食、多尿等症状,体重仍有继续增长,但精神较模型一组好,反应、动作等未见明显迟钝。实验过程中未见动物死亡。一直以高盐、高脂、高糖饮食饲养的针刺1组大鼠(仅针刺干预),经针刺治疗后精神、反应、动作较前有所好转,实验过程中死亡1只。针刺2组大鼠(饮食与针刺干预),经针刺治疗后,精神萎靡,反应迟钝,动作迟缓等较前明显好转,体重增长速度明显降低,实验过程中未有动物死亡。所有死亡动物均解剖后送病理室检查,未发现异常。
2.2.2针刺对IR大鼠模型血糖、血脂、胰岛素敏感指数的影响
在给予高盐、高糖、高脂饮食8周后大鼠血糖、血脂显著升高,与空白对照组比较,差异显著,P＜0.01;胰岛素敏感指数显著降低,与空白对照组比较,P＜0.01。经饮食干预后,模型2组大鼠血糖、血脂等有所下降,胰岛素敏感指数有所回升,与干预前及模型1组大鼠比较,差异显著,P＜0.05;经针刺治疗后的针刺1组,血糖、血脂水平显著下降,与干预前及模型组比较,差异显著,P＜0.05;经针刺及饮食干预治疗后的针刺2组,其血糖及血脂水平下降明显,胰岛素敏感指数显著回升,与干预前及模型组比较,差异显著,P＜0.01;与针刺1组及模型1组比较,差异显著,P＜0.05。
2.2.3针刺对IR大鼠模型胰腺、肝脏形态学的影响
模型1组大鼠胰腺组织部分有黄色混浊现象。光镜观察可见胰岛周边有大量的淋巴细胞浸润,部分胰岛实质内也有炎性细胞浸润,间质结缔组织增生,系膜增厚。模型2组,经4周饮食干预后,大鼠胰腺组织仍有黄色混浊现象。光镜观察可见胰岛周边有明显的淋巴细胞浸润,部分胰岛实质内也有炎性细胞浸润,间质结缔组织增生,系膜增厚。总体病变程度较模型1组相对减轻。
针刺1组大鼠胰腺组织可见正常的腺泡和胰岛结构,部分胰腺周边有明显的炎性细胞浸润,部分胰岛实质内也有炎性细胞浸润;未见明显结缔组织增生,系膜增厚的现象。针刺2组胰腺组织可见正常的腺泡及胰岛结构,部分有轻度的炎性细胞浸润。未见明显结缔组织增生,系膜增厚的现象。正常对照组:肝小叶结构完整,中央静脉居中,肝索向四周呈放射状排列。模型1组:可见弥漫性肝细胞脂肪变性,以小空泡脂肪变为主,肝小叶内有炎细胞浸润。模型2组:可见弥漫性肝细胞脂肪变性,以小空泡脂肪变为主,肝小叶内有炎细胞浸润。针刺1组:可见散在肝细胞脂肪变性,以小空泡脂肪变为主,肝小叶内少许炎细胞浸润。针刺2组:肝小叶结构完整,中央静脉居中,肝索向四周呈放射状排列,未见明显肝细胞脂肪变性,肝小叶无炎细胞浸润。
2.2.4针刺对IR大鼠模型血液流变学的影响
本实验显示:IR大鼠模型血液呈高黏高凝状态:血液黏滞度增高,血细胞聚集性增强。经针刺及饮食干预治疗后,能够有效改善工R模型的血液流变学指标。与空白组比较,模型1组和模型2组的高切变率、低切变率、血浆比粘度、红细胞压积、红细胞电泳时间、红细胞聚集指数等都显著高于空白组(P＜0.01与模型1组比较,针刺1组的高切变率、红细胞压积、红细胞电泳时间、红细胞聚集指数都显著下降(P＜0.01或P＜0.05,针刺2组的高切变率、低切变率、血浆比粘度、红细胞压积、红细胞电泳时间、红细胞聚集指数都显著下降(P＜0.01与模型2组比较,针刺2组的高切变率、低切变率、血浆比粘度、红细胞压积、红细胞电泳时间、红细胞聚集指数都显著下降(P＜0.01)。
2.2.5针刺对IR大鼠模型SOD、MDA、GSH-Px的影响
实验结果显示:IR大鼠血浆氧化-抗氧化系统失衡,氧自由基产物MDA水平显著上升,抗氧化物质SOD、GSH-Px等水平显著下降。经针刺和(或)饮食干预后MDA水平下降,SOD、GSH-Px等水平有所回升,经针刺及饮食干预的针刺2组大鼠效果最好,与模型1组相比,差异显著,P＜0.01,与针刺1组及模型2组相比,差异显著,P＜0.01。提示针刺可能通过调节IR模型大鼠的氧化-抗氧化系统的平衡,起到逆转胰岛素抵抗的作用。
2.2.6针刺对IR大鼠模型TXB2、6-Keto-PGF1α、ET、NO的影响
研究结果显示,IR大鼠模型血浆中,反应血管内皮功能受损的指标:TXB2、ET等血浆水平显著上升,而内皮舒张因子NO及6-Keto-PGF1_α等水平却显著下降,提示IR大鼠模型血管内皮功能受损。经针刺及饮食干预后,6-Keto-PGF1α、NO水平有所回升,TXB_2、ET等下降,与模型1组比较,差异显著,P＜0.01或P＜0.05;与模型2组及针刺1组比较,P＜0.05。而模型2组与针刺1组比较,针刺1组似要优于模型2组,但无统计学意义,P＜0.05。
2.2.7针刺对IR大鼠模型主动脉VEGF表达的影响
模型1组大鼠主动脉切片可见棕黄色阳性表达信号,主要位于细胞质内及细胞外间质;模型2组、针刺1组可见棕黄色阳性表达,但是没有模型1组表达的强烈;针刺2组可见少范围表达,而正常对照组则表达较少。
3结论
(1)高脂、高糖、高盐饮食可成功复制出胰岛素抵抗大鼠模型,该模型能够表现出胰岛素抵抗所应具备的基本特征:高血糖、高血脂、高胰岛素血症、向心性肥胖等。经本研究证实,本模型大鼠血管内皮功能有明显的受损表现,为本研究的顺利开展打下良好的基础。(2)针刺干预可显著改善IR模型胰岛素抵抗:降低IR大鼠血脂、血糖、改善胰岛素抵抗,与模型组对比,差异显著,且优于单纯饮食干预;在针刺干预的基础上结合饮食干预,效果更好。针刺结合饮食干预可修复受损的血管内皮逆转由于胰岛素抵抗,其机制可能与其调节失衡的体内氧化-抗氧化系统,改善血液流变学,降低模型升高的ET、TXB2,升高NO、6-Keto-PGF1_α有关。(3)存在的问题:本模型大鼠主动脉内皮未见确切动脉粥样斑块形成,主动脉VEGF在各组中表达未有显著差别,可能与造模时间有关。(4)下一步研究方向:继续完善如何评价IR模型的血管内皮评价功能指标,从基因组学、蛋白组学或者更高层面进一步深入探讨IR相关并发症的发病机制,探讨针刺及其它方法防治IR及相关并发症的作用机制,并进一步优化治疗方案。
Endothelium Dysfunction as the breakaway ring-joint of Artherosclerosis has an importance effect to happen and development of the disease.In this year we find that the insulin resistance will lead the Endothelium Dysfunction,and participative the happen of the Artherosclerosis.The IR was the metabolic disorder base of diverse disease which correlated with Metabolic syndrome include the glucose tolerance abnormal,type 2 diabetes mellitus,obesity,dyslipidemia and hypertension,it also was a very important reason of the end point incident of eadiovascular and cerebrovascular base diseades such as Atherosclerosis and coronary atherosclerotic heart disease.The overriding effect to the vascular is the chronic complication.Now the heat point of the base investigative of the vascular lesion was "the Dysfunction of Vascular Endothelium",it was said that the Dysfunction of Vascular Endothelium is the cectral link of the vascular lesion and also the origination link.Now protect the Vascular Endothelium,and reverse the damage of the Vascular Endothelium was the central link of prevention and cure vascular lesion,and it also the very difficult link of the Modern Medicine.
Acupuncture as a naturopaths,because it uncomplicated,economical,convenient and efficacious,so it has the superiority for several thousand years to diagnose and treat in the tradition chinese medical science,furthermore many research confirm that acupuncture has a good effect that it can regulate the endocrine metabolic,the dominance had already gradually fadein in therapy many modern disease.Though the work about the acuouncture treat the IR carry out less in nowadays,but the curative effects of acupuncture to the DM, obesity and cerebral infrarcfion was already obtain the same trade or occupation internal and abroad in for a long time.
The clinical and empirical study of the Predecessor had show that,the acupuncture had a certain effect of reverse the IR,the acupuncture can improvability the state of IR model and the dicbetic,can prevention and cure the chronic complication,decrease the develop rate of blood vessel chronic complication that owing to the state of hyperglycosemia,but the study above had not had a system study yet.
The study was based in the grouding of the predecessor' study:use the high glucose, high fat,high salt diet to copy the IR model,and to combine the modern detect technology to investigate the change of the Vascular Endothelium function,and the effect of acupuncture to the change of the Vascular Endothelium function.
This study was include three parts,the literature study:①through study mass of literature about the IR,from the conception of IR,the Epidemiology of IR,the pathologic mechanism and prevention and cure of IR,the IR and the relationship disease,the relationship of IR and the dysfunction endothelium and the mechanisim of the happen and develop to expound the latest study of IR.②the realization and research of progression of the chinese medical science to IR,the research situation of chinese medicine to prevention and cure the IR,especially to analysis the domestic and aboard use the acupunture to prevention and cure the IR,to raise the coming trend of the study,consider that the method of acupuncture was a good mean to improve the IR,at the base of the study of predecessor we emphasized to study the of acupunture to the dysfunction of Vascular Endothelium in IR,inorser that to explored the machanisim of the acupuncture to the IR..
Part one Literature research
Through to massively about the insulin resistance's literature synthetic study,from the insulin resistance concept,the insulin resistance and the related disease related the influencing factor which as well as the insulin resistance,the insulin resistance occurred has the mechanism and the prevention and so on elaborated variously the insulin resistance's newest research development,and has carried on the analysis to the Chinese medicine prevention insulin resistance's research present situation,has carried on the narration specially to the acupunture therapy insulin resistance's
Part two Experimental studies
2.1 Methods
Use the high glucose,high salt,the high fat diet copy the insulin resistance model big mouse,according to the blood sugar,the blood fats,the insulin sensitive index,the related cell factor(TXB_2,6-Keto-PGF1α,ET,NO) and so on judgments makes the mold success or not.To combine the immunohistology,pathology,Radioimmunodetection,etc,modern examination technology observation acupuncture union immunity group study resist the big mouse model blood sugar,the blood fats,the insulin sensitive index,are related the internal organs(liver,pancreatic gland) the morphology influence to the insulin,as well as responds the IR big mouse model blood vessel bast function the index of correlation:Blood rheology target,related cell factor(TXB_2,6-Keto-PGF1α,ET,NO),aorta VEGF expression influence and so on influence,key prominent acupuncture to IR big mouse model blood vessel bast function influence.
2.2 Results
2.2.1 acupuncture to the IR big mouse model general condition and body weight
influence
In the experiment process,the normal control group big mouse body weight quality increases gradually,the state of mind is good,responds keenly,the movement freely,the hair lies flat has the gloss,does not have 1 example death.The 5th week starts,the model 1 group,the model 2 groups,the acupuncture 1 group,the acupuncture 2 group of big mouse personality poikilothermia is suitable,the carriage is obese,is addicted to rests little moves, the big mouse superficial knowledge dishevelled does not have the gloss,the bowel movement quantity normal group are few,the color ash,the nature is soft,the body weight grows quickly,the abdomen is obese.The model 1 group of big mice which by Gao Zhi, Gao Tang,the high salty feed feeds have appeared gradually drink,the multi-food,the polyuria,and the energetic dispirited,the slow reaction,the movement is slow,the body weight growth is later period slow,in the experiment process dies 1.The model 2 groups after changing to the ordinary feed feeds(diet intervention),only the minority big mouse appeared drinks,multi-symptoms and so on food,polyuria,the body weight still had continues to grow,but the spirit compared model group of good,responded that the movement and so on has not seen obviously slow.In the experiment process has not seen the animal death.Continuously by Gao Yan,Gao Zhi,high sugar diet raising acupuncture 1 group of big mice(only acupuncture intervention),before acupuncture treatment the spirit, the response,the movement have the change for the better,in the experiment process die 1. The acupuncture 2 groups of big mice(diet and acupuncture intervention),treats 2 weeks later the acupuncture,the energetic dispirited,the slow reaction,before the movement slow and so on,the obvious change for the better,the body weight rate of rise obviously reduces, in the experiment process has not had the animal death.
2.2.2 The influence of Acupuncture to IR big mouse model blood sugar,blood fats, insulin sensitive index
Gives high glucose,high salt,the high fat diet 8 weeks later,each group of big mouse's blood sugar,the blood fats level obviously elevate,the insulin level obvious drop, compares with the blank control group,the difference is remarkable,p<0.01;The insulin sensitive index obviously reduces,compares with the blank control group,p<0.01.After diet intervention,the model 2 group of big mouse blood sugar level,the blood fats level and so on drop,the insulin sensitive index has the rise,compares with the model 1 group of big mice,the difference is remarkable,p<0.05;After the acupuncture treatment's acupuncture 1 group,the blood sugar,the blood fats level obviously drop,compares before the intervention and the model group,the difference is remarkable,p<0.05;After the acupuncture and the diet intervention treatment's acupuncture 2 groups,its blood sugar and the blood fats level drop obviously,the insulin sensitive index obviously rises again, compares before the intervention and the model group,the difference is remarkable,p<0.01; 1 group and the model 1 group compares with the acupuncture,the difference is remarkable,p＜0.05.
2.2.3 The influence of Acupuncture to the IR big mouse model pancreatic gland,liver morphology's
The model 1 group of big mouse pancreatic gland organization part has the yellow muddy phenomenon.The light microscope observation obvious island of langerhans peripheral has the massive lymphocyte infiltration,in the partial island of langerhans essence also has the inflammatory cell infiltration,the mesenchymal knot contracts the organization proliferation,is the membrane accumulation(Figure 3).Model 2 groups,after 4 week diet intervention,the big mouse pancreatic gland organization still had the yellow muddy phenomenon.The light microscope observation obvious island of langerhans peripheral has the obvious lymphocyte infiltration,in the partial island of langerhans essence also has the inflammatory cell infiltration,the mesenchymal knot contracts the organization proliferation,is the membrane accumulation.The overall pathological change degree compares the model 1 group to reduce relatively.The acupuncture 1 group of big mouse pancreatic gland organization obviously normal acinus and the island of langerhans structure,the partial pancreatic gland peripheral have the obvious inflammatory cell infiltration,in the partial island of langerhans essence also has the inflammatory cell infiltration;Has not seen the obvious knot to contract the organization proliferation,is the membrane accumulation phenomenon(Figure 4).the acupuncture 2 group of pancreatic gland organization obviously normal acinus and the island of langerhans structure,the part has the mild inflammatory cell infiltration.Has not seen the obvious knot to contract the organization proliferation,is the membrane accumulation phenomenon.Normal control group:The hepatic lobe structure is complete,the central vein comes,and the liver rope assumes the radiated arrangement to four weeks.Model 1 group:Obviously the proliferating liver cell fatty degeneration,becomes the host by the small vacuole fat,in the hepatic lobe has the phlogocyte to infiltrate(Figure 1).Model 2 groups:Obviously the proliferating liver cell fatty degeneration,becomes the host by the small vacuole fat,in the hepatic lobe has the phlogocyte to infiltrate(Figure 2).Acupuncture 1 group:Obviously disperses in the liver cell fatty degeneration,becomes the host by the small vacuole fat,in the hepatic lobe the little phlogocyte infiltration(Figure 2).Acupuncture 2 groups:The hepatic lobe structure is complete,the central vein comes,the liver rope assumes the radiated arrangement to four weeks,has not seen the obvious liver cell fatty degeneration, the hepatic lobe non-phlogocyte infiltration(Figure 2).
2.2.4 Acupuncture to IR big mouse model blood rheology influence
This experiment demonstrated:The IR big mouse model blood assumes Gao Niangao to congeal the condition:The blood mounts the stagnation markup,the blood corpuscle accumulation enhancement.After acupuncture and diet intervention treatment,can improve the IR model effectively the blood rheology target.Compares with the blank group,the model 1 group and the model 2 groups of high shears rate,the low shear rate,the blood plasma specific viscosity,the red blood cell press the product,the red blood cell electrophoresis time,the red blood cell accumulation index and so on obviously to be higher than the blank group(p＜0.01).Compares with the model 1 group,the acupuncture 1 group of high shears rate,the red blood cell press the product,the red blood cell electrophoresis time,the red blood cell accumulation index obviously to drop(19＜0.01 or p＜0.05),the acupuncture 2 groups of high shears rate,the low shear rate,the blood plasma specific viscosity,the red blood cell press the product,the red blood cell electrophoresis time,the red blood cell accumulation index obviously to drop(p＜0.01).Compares with the model 2 groups,the acupuncture 2 groups of high shears rate,the low shear rate,the blood plasma specific viscosity,the red blood cell press the product,the red blood cell electrophoresis time,the red blood cell accumulation index obviously to drop(p＜0.01).
2.2.5 acupuncture to IR big mouse model SOD,MDA,GSH-Px influence
The experimental result showed:The IR big mouse blood plasma oxidation - oxidation resistance system is unbalanced,the oxygen free radical product MDA level obviously rises, oxidation resistance levels and so on material SOD,GSH-Px obviously drop.After acupuncture and(or) diet intervention the MDA level drops,levels and so on SOD, GSH-Px have the rise,is best after the acupuncture and the diet intervention's acupuncture 2 group of big mouse effect,compares with the model 1 group,the difference is remarkable, 1 group and the model 2 groups compares with the acupuncture,the difference is remarkable.The prompt acupuncture possibly through adjusts IR model big mouse's oxidized - oxidation resistance system's balanced,plays the reversal insulin resistance the role.
2.2.7 acupuncture to IR big mouse model aorta VEGF expression influence
The model 1 group of big mouse aorta slice obvious yellowish brown color masculine gender expresses the signal,is mainly located in the cytoplasm and the extracellular is mesenchymal;Model 2 groups,the acupuncture 1 group of obvious yellowish brown color masculine genders express,but does not have the intensity which the model 1 group expresses;The acupuncture 2 groups may the becoming fewer scope express,but the normal control group expresses few.
3 Conclusions
①High glucose,high salt,the high fat diet may succeed duplicate the insulin to resist the big mouse model,this model can display the essential feature which the insulin resistance should have:Hyperglycemia,high blood fats,high insulin blood sickness,centripetalism obese and so on.Confirmed after this research that this model big mouse blood vessel bast function has obviously suffers injury the performance,builds the good foundation for this research's smooth development.②The acupuncture intervention may obviously improve the IR model insulin resistance:Reduces the IR big mouse blood fats,the blood sugar,the improvement insulin resistance,with the model group contrast,the difference is remarkable, and surpasses the pure diet intervention;Unifies the diet intervention in the acupuncture intervention's foundation,the effect is better.The acupuncture union diet intervention may repair the blood vessel bast which suffers injury to reverse as a result of the insulin resistance,its mechanism possible with its adjustment unbalanced in vivo oxidation -oxidation resistance system,improvement blood rheology,reduces ET which,TXB2 the model elevates,elevates NO,6-Keto-PGF1αto concern.③Existence question:This model big mouse aorta bast has not seen the accurate artery gruel type mottling formation,aorta VEGF expresses in each group has not had the remarkable difference,possible with to make the mold time to concern.Next step research direction:How continues to consummate to appraise the IR model the blood vessel bast appraisal function target,from genomics,the protein group study or a higher stratification plane further thoroughly discusses the IR related complication the pathogenesis,the discussion acupuncture and other methods prevents and controls IR and the related complication function mechanism, and further optimizes the therapeutic schedule.
针灸作为一种自然疗法,因其简、便、验、廉等优势在几千年的中医传统诊疗中起着十分重要的作用,且众多的研究也证实针灸具有良好的调节内分泌代谢的作用,在治疗诸多现代疾病中已逐渐显示出优势。虽然目前针刺治疗胰岛素抵抗等研究工作开展得较少,但针刺对糖尿病、肥胖、脑梗塞等相关疾病的疗效早已得到了国内外同行的公认。
前人的临床及实验研究表明,针刺对胰岛素抵抗具有一定的逆转效应——通过针刺干预可改善动物模型及糖尿病患者的胰岛素抵抗状态,并可防治慢性并发症的产生与发展,降低由于长期高血糖状态引发的血管性慢性并发症的产生。但目前研究对于以上作用的机制并未进行系统并有针对性的研究。
本研究是前人研究的基础上,以高糖、高脂、高盐饮食复制胰岛素抵抗动物实验模型,结合现代检测技术,深入探讨胰岛素抵抗状态下血管内皮功能的变化状况及针刺对内皮功能变化的影响作用。
全文分文献研究、实验研究和小结三大部分进行。
1文献研究
通过对大量关于胰岛素抵抗的文献综合研究,从胰岛素抵抗概念、胰岛素抵抗与相关疾病关系、胰岛素抵抗发生的影响因素以及胰岛素抵抗发生机理及防治等多方面阐述了胰岛素抵抗的最新研究进展,并对中医药防治胰岛素抵抗的研究现状进行了分析,特别对针灸治疗胰岛素抵抗的国内外研究进展进行了评述,提出今后的研究方向,认为针刺不失为改善胰岛素抵抗的有效方法之一,应加强对其作用机理的深入研究和探讨。
2实验研究
2.1方法
(1)实验分组
将60只雄性sD大鼠[体重(200±20)g以普通饲料进行适应性饲养1周,按体质量随机分为5组,每组12只,分别为空白对照组(Blank Group)、模型1组(ModelGroup 1)、模型2组(Model Group 2)、针刺1组(Acupuncture Therapy Group 1,AT1)和针刺2组(Acupuncture Therapy Group 2,AT2)。空白对照组以普通饲料喂养,其它各组均以高脂高糖高盐饲料饲养。从第5周开始至实验结束,每周测1次体重;从第4周开始,每隔1周空白对照组和模型1组大鼠从眼眶静脉窦采血1次,检测FPG、INS,并计算ISI进行对比,确定造模是否成功。第8周造模成功后,空白对照组、模型2组及针刺2组继续以普通饲料喂养4周,其中针刺2组同时给予针刺治疗,1次/d,连续4周;模型1组、针刺1组继续以高脂高糖高盐饲料喂养4周,其中针刺1组同时给予针刺治疗,1次/d,连续4周。
(2)取穴及针刺方法
取穴:穴位选用“脂三针”(手厥阴心包经“内关”、足阳明胃经“足三里”、足太阴脾经“三阴交”)以及足太阳膀胱经“肾俞”穴。其定位参照大鼠的常用针灸穴位:“内关”位于前肢内侧,离腕关节约3mm左右的尺挠骨缝间;“足三里”位于大鼠后肢膝关节外下方当排骨小头下约5mm处;“三阴交”位于大鼠后肢内踝尖直上10mm处;“肾俞”位于大鼠后背第二腰椎下旁开5mm之两旁肋间。
刺法:内关、足三里、三阴交均以30号1寸毫针(华佗牌,苏州医疗用品厂生产),沿皮斜刺8mm,针尖朝向肢体近端,肾俞直刺5mm,在内关、足三里穴,接电针治疗,将针柄分别连接至电针仪的电极上,采用青岛华声仪器厂生产的G6805电针仪,疏密波,频率5～10Hz强度以肌肉轻微抖为度,电压3～5v,时间持续30分钟。每天1次,连续治疗28天。
第12周实验结束后取标本进行相关指标的检测,结合免疫组学、病理、放射免疫检测等现代检测技术观察针刺对胰岛素抵抗大鼠模型、血脂、相关脏器(肝脏、胰腺)的形态学的影响,以及反应IR大鼠模型血管内皮功能的相关指标:血液流变学指标、相关细胞因子(TXB_2、6-Keto-PGF_(1α)、ET、NO)、主动脉VEGF表达的影响等的影响,重点突出针刺对IR大鼠模型血管内皮功能的影响。
2.2结果
2.2.1针刺对IR大鼠模型一般状况及体重的影响
实验过程中,正常对照组大鼠体质量逐渐增加,精神状态良好,反应灵敏,动作自如,毛发平伏有光泽,无1例死亡。第5周开始模型1、2组、针刺1组、针刺2组大鼠性情变温顺,体态肥胖,嗜睡少动,大鼠皮毛蓬乱而无光泽,大便量较正常组偏少,色灰,质较软,体重增长较快,腹部肥胖。一直以高脂、高糖、高盐饲料喂养的模型1组大鼠逐渐出现多饮、多食、多尿,且精神萎靡,反应迟钝,动作迟缓,后期体重增长缓慢,实验过程中死亡1只。模型2组在改用普通饲料喂养后(饮食干预),仅少数大鼠出现多饮、多食、多尿等症状,体重仍有继续增长,但精神较模型一组好,反应、动作等未见明显迟钝。实验过程中未见动物死亡。一直以高盐、高脂、高糖饮食饲养的针刺1组大鼠(仅针刺干预),经针刺治疗后精神、反应、动作较前有所好转,实验过程中死亡1只。针刺2组大鼠(饮食与针刺干预),经针刺治疗后,精神萎靡,反应迟钝,动作迟缓等较前明显好转,体重增长速度明显降低,实验过程中未有动物死亡。所有死亡动物均解剖后送病理室检查,未发现异常。
2.2.2针刺对IR大鼠模型血糖、血脂、胰岛素敏感指数的影响
在给予高盐、高糖、高脂饮食8周后大鼠血糖、血脂显著升高,与空白对照组比较,差异显著,P＜0.01;胰岛素敏感指数显著降低,与空白对照组比较,P＜0.01。经饮食干预后,模型2组大鼠血糖、血脂等有所下降,胰岛素敏感指数有所回升,与干预前及模型1组大鼠比较,差异显著,P＜0.05;经针刺治疗后的针刺1组,血糖、血脂水平显著下降,与干预前及模型组比较,差异显著,P＜0.05;经针刺及饮食干预治疗后的针刺2组,其血糖及血脂水平下降明显,胰岛素敏感指数显著回升,与干预前及模型组比较,差异显著,P＜0.01;与针刺1组及模型1组比较,差异显著,P＜0.05。
2.2.3针刺对IR大鼠模型胰腺、肝脏形态学的影响
模型1组大鼠胰腺组织部分有黄色混浊现象。光镜观察可见胰岛周边有大量的淋巴细胞浸润,部分胰岛实质内也有炎性细胞浸润,间质结缔组织增生,系膜增厚。模型2组,经4周饮食干预后,大鼠胰腺组织仍有黄色混浊现象。光镜观察可见胰岛周边有明显的淋巴细胞浸润,部分胰岛实质内也有炎性细胞浸润,间质结缔组织增生,系膜增厚。总体病变程度较模型1组相对减轻。
针刺1组大鼠胰腺组织可见正常的腺泡和胰岛结构,部分胰腺周边有明显的炎性细胞浸润,部分胰岛实质内也有炎性细胞浸润;未见明显结缔组织增生,系膜增厚的现象。针刺2组胰腺组织可见正常的腺泡及胰岛结构,部分有轻度的炎性细胞浸润。未见明显结缔组织增生,系膜增厚的现象。正常对照组:肝小叶结构完整,中央静脉居中,肝索向四周呈放射状排列。模型1组:可见弥漫性肝细胞脂肪变性,以小空泡脂肪变为主,肝小叶内有炎细胞浸润。模型2组:可见弥漫性肝细胞脂肪变性,以小空泡脂肪变为主,肝小叶内有炎细胞浸润。针刺1组:可见散在肝细胞脂肪变性,以小空泡脂肪变为主,肝小叶内少许炎细胞浸润。针刺2组:肝小叶结构完整,中央静脉居中,肝索向四周呈放射状排列,未见明显肝细胞脂肪变性,肝小叶无炎细胞浸润。
2.2.4针刺对IR大鼠模型血液流变学的影响
本实验显示:IR大鼠模型血液呈高黏高凝状态:血液黏滞度增高,血细胞聚集性增强。经针刺及饮食干预治疗后,能够有效改善工R模型的血液流变学指标。与空白组比较,模型1组和模型2组的高切变率、低切变率、血浆比粘度、红细胞压积、红细胞电泳时间、红细胞聚集指数等都显著高于空白组(P＜0.01与模型1组比较,针刺1组的高切变率、红细胞压积、红细胞电泳时间、红细胞聚集指数都显著下降(P＜0.01或P＜0.05,针刺2组的高切变率、低切变率、血浆比粘度、红细胞压积、红细胞电泳时间、红细胞聚集指数都显著下降(P＜0.01与模型2组比较,针刺2组的高切变率、低切变率、血浆比粘度、红细胞压积、红细胞电泳时间、红细胞聚集指数都显著下降(P＜0.01)。
2.2.5针刺对IR大鼠模型SOD、MDA、GSH-Px的影响
实验结果显示:IR大鼠血浆氧化-抗氧化系统失衡,氧自由基产物MDA水平显著上升,抗氧化物质SOD、GSH-Px等水平显著下降。经针刺和(或)饮食干预后MDA水平下降,SOD、GSH-Px等水平有所回升,经针刺及饮食干预的针刺2组大鼠效果最好,与模型1组相比,差异显著,P＜0.01,与针刺1组及模型2组相比,差异显著,P＜0.01。提示针刺可能通过调节IR模型大鼠的氧化-抗氧化系统的平衡,起到逆转胰岛素抵抗的作用。
2.2.6针刺对IR大鼠模型TXB2、6-Keto-PGF1α、ET、NO的影响
研究结果显示,IR大鼠模型血浆中,反应血管内皮功能受损的指标:TXB2、ET等血浆水平显著上升,而内皮舒张因子NO及6-Keto-PGF1_α等水平却显著下降,提示IR大鼠模型血管内皮功能受损。经针刺及饮食干预后,6-Keto-PGF1α、NO水平有所回升,TXB_2、ET等下降,与模型1组比较,差异显著,P＜0.01或P＜0.05;与模型2组及针刺1组比较,P＜0.05。而模型2组与针刺1组比较,针刺1组似要优于模型2组,但无统计学意义,P＜0.05。
2.2.7针刺对IR大鼠模型主动脉VEGF表达的影响
模型1组大鼠主动脉切片可见棕黄色阳性表达信号,主要位于细胞质内及细胞外间质;模型2组、针刺1组可见棕黄色阳性表达,但是没有模型1组表达的强烈;针刺2组可见少范围表达,而正常对照组则表达较少。
3结论
(1)高脂、高糖、高盐饮食可成功复制出胰岛素抵抗大鼠模型,该模型能够表现出胰岛素抵抗所应具备的基本特征:高血糖、高血脂、高胰岛素血症、向心性肥胖等。经本研究证实,本模型大鼠血管内皮功能有明显的受损表现,为本研究的顺利开展打下良好的基础。(2)针刺干预可显著改善IR模型胰岛素抵抗:降低IR大鼠血脂、血糖、改善胰岛素抵抗,与模型组对比,差异显著,且优于单纯饮食干预;在针刺干预的基础上结合饮食干预,效果更好。针刺结合饮食干预可修复受损的血管内皮逆转由于胰岛素抵抗,其机制可能与其调节失衡的体内氧化-抗氧化系统,改善血液流变学,降低模型升高的ET、TXB2,升高NO、6-Keto-PGF1_α有关。(3)存在的问题:本模型大鼠主动脉内皮未见确切动脉粥样斑块形成,主动脉VEGF在各组中表达未有显著差别,可能与造模时间有关。(4)下一步研究方向:继续完善如何评价IR模型的血管内皮评价功能指标,从基因组学、蛋白组学或者更高层面进一步深入探讨IR相关并发症的发病机制,探讨针刺及其它方法防治IR及相关并发症的作用机制,并进一步优化治疗方案。
Endothelium Dysfunction as the breakaway ring-joint of Artherosclerosis has an importance effect to happen and development of the disease.In this year we find that the insulin resistance will lead the Endothelium Dysfunction,and participative the happen of the Artherosclerosis.The IR was the metabolic disorder base of diverse disease which correlated with Metabolic syndrome include the glucose tolerance abnormal,type 2 diabetes mellitus,obesity,dyslipidemia and hypertension,it also was a very important reason of the end point incident of eadiovascular and cerebrovascular base diseades such as Atherosclerosis and coronary atherosclerotic heart disease.The overriding effect to the vascular is the chronic complication.Now the heat point of the base investigative of the vascular lesion was "the Dysfunction of Vascular Endothelium",it was said that the Dysfunction of Vascular Endothelium is the cectral link of the vascular lesion and also the origination link.Now protect the Vascular Endothelium,and reverse the damage of the Vascular Endothelium was the central link of prevention and cure vascular lesion,and it also the very difficult link of the Modern Medicine.
Acupuncture as a naturopaths,because it uncomplicated,economical,convenient and efficacious,so it has the superiority for several thousand years to diagnose and treat in the tradition chinese medical science,furthermore many research confirm that acupuncture has a good effect that it can regulate the endocrine metabolic,the dominance had already gradually fadein in therapy many modern disease.Though the work about the acuouncture treat the IR carry out less in nowadays,but the curative effects of acupuncture to the DM, obesity and cerebral infrarcfion was already obtain the same trade or occupation internal and abroad in for a long time.
The clinical and empirical study of the Predecessor had show that,the acupuncture had a certain effect of reverse the IR,the acupuncture can improvability the state of IR model and the dicbetic,can prevention and cure the chronic complication,decrease the develop rate of blood vessel chronic complication that owing to the state of hyperglycosemia,but the study above had not had a system study yet.
The study was based in the grouding of the predecessor' study:use the high glucose, high fat,high salt diet to copy the IR model,and to combine the modern detect technology to investigate the change of the Vascular Endothelium function,and the effect of acupuncture to the change of the Vascular Endothelium function.
This study was include three parts,the literature study:①through study mass of literature about the IR,from the conception of IR,the Epidemiology of IR,the pathologic mechanism and prevention and cure of IR,the IR and the relationship disease,the relationship of IR and the dysfunction endothelium and the mechanisim of the happen and develop to expound the latest study of IR.②the realization and research of progression of the chinese medical science to IR,the research situation of chinese medicine to prevention and cure the IR,especially to analysis the domestic and aboard use the acupunture to prevention and cure the IR,to raise the coming trend of the study,consider that the method of acupuncture was a good mean to improve the IR,at the base of the study of predecessor we emphasized to study the of acupunture to the dysfunction of Vascular Endothelium in IR,inorser that to explored the machanisim of the acupuncture to the IR..
Part one Literature research
Through to massively about the insulin resistance's literature synthetic study,from the insulin resistance concept,the insulin resistance and the related disease related the influencing factor which as well as the insulin resistance,the insulin resistance occurred has the mechanism and the prevention and so on elaborated variously the insulin resistance's newest research development,and has carried on the analysis to the Chinese medicine prevention insulin resistance's research present situation,has carried on the narration specially to the acupunture therapy insulin resistance's
Part two Experimental studies
2.1 Methods
Use the high glucose,high salt,the high fat diet copy the insulin resistance model big mouse,according to the blood sugar,the blood fats,the insulin sensitive index,the related cell factor(TXB_2,6-Keto-PGF1α,ET,NO) and so on judgments makes the mold success or not.To combine the immunohistology,pathology,Radioimmunodetection,etc,modern examination technology observation acupuncture union immunity group study resist the big mouse model blood sugar,the blood fats,the insulin sensitive index,are related the internal organs(liver,pancreatic gland) the morphology influence to the insulin,as well as responds the IR big mouse model blood vessel bast function the index of correlation:Blood rheology target,related cell factor(TXB_2,6-Keto-PGF1α,ET,NO),aorta VEGF expression influence and so on influence,key prominent acupuncture to IR big mouse model blood vessel bast function influence.
2.2 Results
2.2.1 acupuncture to the IR big mouse model general condition and body weight
influence
In the experiment process,the normal control group big mouse body weight quality increases gradually,the state of mind is good,responds keenly,the movement freely,the hair lies flat has the gloss,does not have 1 example death.The 5th week starts,the model 1 group,the model 2 groups,the acupuncture 1 group,the acupuncture 2 group of big mouse personality poikilothermia is suitable,the carriage is obese,is addicted to rests little moves, the big mouse superficial knowledge dishevelled does not have the gloss,the bowel movement quantity normal group are few,the color ash,the nature is soft,the body weight grows quickly,the abdomen is obese.The model 1 group of big mice which by Gao Zhi, Gao Tang,the high salty feed feeds have appeared gradually drink,the multi-food,the polyuria,and the energetic dispirited,the slow reaction,the movement is slow,the body weight growth is later period slow,in the experiment process dies 1.The model 2 groups after changing to the ordinary feed feeds(diet intervention),only the minority big mouse appeared drinks,multi-symptoms and so on food,polyuria,the body weight still had continues to grow,but the spirit compared model group of good,responded that the movement and so on has not seen obviously slow.In the experiment process has not seen the animal death.Continuously by Gao Yan,Gao Zhi,high sugar diet raising acupuncture 1 group of big mice(only acupuncture intervention),before acupuncture treatment the spirit, the response,the movement have the change for the better,in the experiment process die 1. The acupuncture 2 groups of big mice(diet and acupuncture intervention),treats 2 weeks later the acupuncture,the energetic dispirited,the slow reaction,before the movement slow and so on,the obvious change for the better,the body weight rate of rise obviously reduces, in the experiment process has not had the animal death.
2.2.2 The influence of Acupuncture to IR big mouse model blood sugar,blood fats, insulin sensitive index
Gives high glucose,high salt,the high fat diet 8 weeks later,each group of big mouse's blood sugar,the blood fats level obviously elevate,the insulin level obvious drop, compares with the blank control group,the difference is remarkable,p<0.01;The insulin sensitive index obviously reduces,compares with the blank control group,p<0.01.After diet intervention,the model 2 group of big mouse blood sugar level,the blood fats level and so on drop,the insulin sensitive index has the rise,compares with the model 1 group of big mice,the difference is remarkable,p<0.05;After the acupuncture treatment's acupuncture 1 group,the blood sugar,the blood fats level obviously drop,compares before the intervention and the model group,the difference is remarkable,p<0.05;After the acupuncture and the diet intervention treatment's acupuncture 2 groups,its blood sugar and the blood fats level drop obviously,the insulin sensitive index obviously rises again, compares before the intervention and the model group,the difference is remarkable,p<0.01; 1 group and the model 1 group compares with the acupuncture,the difference is remarkable,p＜0.05.
2.2.3 The influence of Acupuncture to the IR big mouse model pancreatic gland,liver morphology's
The model 1 group of big mouse pancreatic gland organization part has the yellow muddy phenomenon.The light microscope observation obvious island of langerhans peripheral has the massive lymphocyte infiltration,in the partial island of langerhans essence also has the inflammatory cell infiltration,the mesenchymal knot contracts the organization proliferation,is the membrane accumulation(Figure 3).Model 2 groups,after 4 week diet intervention,the big mouse pancreatic gland organization still had the yellow muddy phenomenon.The light microscope observation obvious island of langerhans peripheral has the obvious lymphocyte infiltration,in the partial island of langerhans essence also has the inflammatory cell infiltration,the mesenchymal knot contracts the organization proliferation,is the membrane accumulation.The overall pathological change degree compares the model 1 group to reduce relatively.The acupuncture 1 group of big mouse pancreatic gland organization obviously normal acinus and the island of langerhans structure,the partial pancreatic gland peripheral have the obvious inflammatory cell infiltration,in the partial island of langerhans essence also has the inflammatory cell infiltration;Has not seen the obvious knot to contract the organization proliferation,is the membrane accumulation phenomenon(Figure 4).the acupuncture 2 group of pancreatic gland organization obviously normal acinus and the island of langerhans structure,the part has the mild inflammatory cell infiltration.Has not seen the obvious knot to contract the organization proliferation,is the membrane accumulation phenomenon.Normal control group:The hepatic lobe structure is complete,the central vein comes,and the liver rope assumes the radiated arrangement to four weeks.Model 1 group:Obviously the proliferating liver cell fatty degeneration,becomes the host by the small vacuole fat,in the hepatic lobe has the phlogocyte to infiltrate(Figure 1).Model 2 groups:Obviously the proliferating liver cell fatty degeneration,becomes the host by the small vacuole fat,in the hepatic lobe has the phlogocyte to infiltrate(Figure 2).Acupuncture 1 group:Obviously disperses in the liver cell fatty degeneration,becomes the host by the small vacuole fat,in the hepatic lobe the little phlogocyte infiltration(Figure 2).Acupuncture 2 groups:The hepatic lobe structure is complete,the central vein comes,the liver rope assumes the radiated arrangement to four weeks,has not seen the obvious liver cell fatty degeneration, the hepatic lobe non-phlogocyte infiltration(Figure 2).
2.2.4 Acupuncture to IR big mouse model blood rheology influence
This experiment demonstrated:The IR big mouse model blood assumes Gao Niangao to congeal the condition:The blood mounts the stagnation markup,the blood corpuscle accumulation enhancement.After acupuncture and diet intervention treatment,can improve the IR model effectively the blood rheology target.Compares with the blank group,the model 1 group and the model 2 groups of high shears rate,the low shear rate,the blood plasma specific viscosity,the red blood cell press the product,the red blood cell electrophoresis time,the red blood cell accumulation index and so on obviously to be higher than the blank group(p＜0.01).Compares with the model 1 group,the acupuncture 1 group of high shears rate,the red blood cell press the product,the red blood cell electrophoresis time,the red blood cell accumulation index obviously to drop(19＜0.01 or p＜0.05),the acupuncture 2 groups of high shears rate,the low shear rate,the blood plasma specific viscosity,the red blood cell press the product,the red blood cell electrophoresis time,the red blood cell accumulation index obviously to drop(p＜0.01).Compares with the model 2 groups,the acupuncture 2 groups of high shears rate,the low shear rate,the blood plasma specific viscosity,the red blood cell press the product,the red blood cell electrophoresis time,the red blood cell accumulation index obviously to drop(p＜0.01).
2.2.5 acupuncture to IR big mouse model SOD,MDA,GSH-Px influence
The experimental result showed:The IR big mouse blood plasma oxidation - oxidation resistance system is unbalanced,the oxygen free radical product MDA level obviously rises, oxidation resistance levels and so on material SOD,GSH-Px obviously drop.After acupuncture and(or) diet intervention the MDA level drops,levels and so on SOD, GSH-Px have the rise,is best after the acupuncture and the diet intervention's acupuncture 2 group of big mouse effect,compares with the model 1 group,the difference is remarkable, 1 group and the model 2 groups compares with the acupuncture,the difference is remarkable.The prompt acupuncture possibly through adjusts IR model big mouse's oxidized - oxidation resistance system's balanced,plays the reversal insulin resistance the role.
2.2.7 acupuncture to IR big mouse model aorta VEGF expression influence
The model 1 group of big mouse aorta slice obvious yellowish brown color masculine gender expresses the signal,is mainly located in the cytoplasm and the extracellular is mesenchymal;Model 2 groups,the acupuncture 1 group of obvious yellowish brown color masculine genders express,but does not have the intensity which the model 1 group expresses;The acupuncture 2 groups may the becoming fewer scope express,but the normal control group expresses few.
3 Conclusions
①High glucose,high salt,the high fat diet may succeed duplicate the insulin to resist the big mouse model,this model can display the essential feature which the insulin resistance should have:Hyperglycemia,high blood fats,high insulin blood sickness,centripetalism obese and so on.Confirmed after this research that this model big mouse blood vessel bast function has obviously suffers injury the performance,builds the good foundation for this research's smooth development.②The acupuncture intervention may obviously improve the IR model insulin resistance:Reduces the IR big mouse blood fats,the blood sugar,the improvement insulin resistance,with the model group contrast,the difference is remarkable, and surpasses the pure diet intervention;Unifies the diet intervention in the acupuncture intervention's foundation,the effect is better.The acupuncture union diet intervention may repair the blood vessel bast which suffers injury to reverse as a result of the insulin resistance,its mechanism possible with its adjustment unbalanced in vivo oxidation -oxidation resistance system,improvement blood rheology,reduces ET which,TXB2 the model elevates,elevates NO,6-Keto-PGF1αto concern.③Existence question:This model big mouse aorta bast has not seen the accurate artery gruel type mottling formation,aorta VEGF expresses in each group has not had the remarkable difference,possible with to make the mold time to concern.Next step research direction:How continues to consummate to appraise the IR model the blood vessel bast appraisal function target,from genomics,the protein group study or a higher stratification plane further thoroughly discusses the IR related complication the pathogenesis,the discussion acupuncture and other methods prevents and controls IR and the related complication function mechanism, and further optimizes the therapeutic schedule.
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