【作者】 谭欣；

【导师】 裴凌；

【作者基本信息】 中国医科大学 ， 麻醉学， 2008， 硕士

【摘要】 前言胰岛素抵抗（IR）是指一定量的胰岛素产生的生物学效应低于预计水平导致胰岛素的外周靶组织（主要为骨骼肌、肝脏和脂肪组织）对内源性或外源性胰岛素的敏感性和反应性降低,导致生理剂量的胰岛素产生低于正常的生理效应,是一种异常的病理生理状态,是许多临床疾病共同的危险因素,已成为近年来医学界多学科共同感兴趣的研究热点。IR在创伤后非常普遍,围手术期内由于麻醉、手术操作、失血等一系列刺激因素往往对机体造成强烈的应激,使体内肾上腺素、胰高血糖素等胰岛素拮抗激素分泌增加,导致糖代谢降低,外周组织葡萄糖利用减少,而β细胞分泌和肝糖输出增加,从而导致高血糖症和高胰岛素血症同时出现,血糖升高作为机体对创伤的一种保护性反应,可保证脑细胞、红细胞等的血糖供应,以维持正常的细胞功能,但持续血糖升高往往产生不良后果,高血糖可以使组织对胰岛素的敏感性降低,进而引起糖脂代谢紊乱,破坏机体内环境的稳定,使机体抗感染、抗休克的能力显著降低,给患者的术后恢复和预后带来不良影响。因此,探讨创伤引起的IR的发病机制,对采取有效措施,改善病人的代谢状况具有重要的意义。本研究通过观察麻醉前、术后、术后1天及术后3天血胰岛素敏感性指数的变化,探讨围手术期IR的程度与手术创伤程度的关系,为临床围手术期采取恰当的处理以降低或缩短术后IR的时间提供理论依据。目的通过观察麻醉前及术后不同时间胰岛素敏感性指数的变化,探讨围手术期IR的程度与手术创伤程度的关系。材料与方法1、一般资料60例有完整病历资料、无糖尿病史的普外及妇科腹部择期全麻手术,ASAⅠ～Ⅱ级,年龄18～80岁,体温正常,体重50～85 kg（波动范围要求≤20%标准体重）,术前各项常规化验检查均无明显异常,无心、肺、肝、肾及神经肌肉系统疾病,无酸碱平衡和水电解质紊乱。对所有病例记录BMI、POSSUM生理学评分（包含12项生理学指标）、手术创伤度评分（包含6项指标:手术大小、手术次数、术中失血量、腹腔污染程度、恶性肿瘤、手术类别）,采取研究后分组方法,根据手术创伤度评分,分3组,Ⅰ组:手术创伤度≤7分;Ⅱ组:手术创伤度8～10分;Ⅲ组:手术创伤度＞10分。2、试剂和仪器除常规麻醉药品及器材外另需:西门子ADVIA Centaur全自动化学发光分析仪（德国）日立7170A全自动生化分析仪（日本）中佳牌KDC-40低速离心机（科大创新中佳分公司）3、麻醉方法患者均无术前用药,静脉注射咪达唑仑5mg、芬太尼5μg/kg、异丙酚2～2.5mg/kg、维库溴铵0.1mg/kg,进行麻醉诱导,气管插管成功后用Datex-OhmedaS/5麻醉机行机械通气,呼吸频率10～14次/分,潮气量8～10ml/kg,维持EtCO₂在30～45mmHg。术中吸入异氟烷,维持呼气末MAC在0.8～1.0之间,间断注射芬太尼和维库溴铵维持麻醉平稳。4、监测方法麻醉机选用Datex-Ohmeda S/5 Aespire（含ISO）,应用Datex-Ohmeda S/5CAM紧凑型麻醉监护仪监测无创血压（BP）、心电图（ECG）、脉搏血氧饱和度（SpO₂）。记录血流动力学指标收缩压、舒张压、平均动脉压,呼气末CO₂浓度（EtCO₂）,呼气末麻醉药浓度（MAC）。5、标本采集分别在麻醉诱导前（T₀）、手术结束拔出气管导管后（T₁）、术后第一天晨空腹（T₂）和术后第三天晨空腹（T₃）采集病人外周静脉血5ml,置于BD SSTⅡ惰性分离胶真空采血管中,送入实验室进行血浆葡萄糖和血浆胰岛素检测。6、标本检测（1）血浆葡萄糖检测:使用己糖激酶法测定血浆葡萄糖:2.5ml静脉血,置于BD SSTⅡ惰性分离胶的真空采血管中,静置后低速离心（3500转/分）5min,取上层血清置于尖头塑料管中,12小时以内上机自动检测。仪器型号:日立7170A全自动生化分析仪,试剂盒为法国医杰公司生产,批号为070102。正常参考范围:4.0～6.38 mmol/L。（2）血浆胰岛素检测:使用化学发光免疫法检测血浆胰岛素:2.5ml静脉血,置于BD SSTⅡ惰性分离胶的真空采血管中,37℃水浴,温育10min,离心分离血清（3500转/分）5min,取上层血清置于尖头塑料管中,上机自动检测。仪器型号:西门子ADVIA Centaur全自动化学发光分析仪。试剂盒为法国医杰公司生产,批号为061120。参考值:3.0～23.0 mU/L。7、统计分析用SPSS13.0软件包进行统计学分析。计量资料以（（?）±S）表示,计数资料用x²检验,组间各样本比较采用方差分析及非参数检验（K-W）。P＜0.05表示差异有统计学意义。结果结果显示,不同手术创伤度评分组（Ⅰ、Ⅱ和Ⅲ组）在年龄、性别比、POSSUM生理学评分和BMI间差异无统计学意义（P＞0.05）。从统计结果看,手术结束后24h,Ⅱ组ΔISI平均下降26.82%,Ⅲ组平均下降可达39.46%,而Ⅰ组下降仅为15.07%,组间差异有统计学意义（P＜0.05）。结论IR与手术程度呈正相关,创伤越大,IR越大,可以看出在术后存在IR,术后24h左右达高峰,随患者恢复而逐渐下降,但手术创伤越大,IR持续的时间也将越长。更多还原

【Abstract】 IntroductionThe insulin resistance means the biology effect produced by one fixed amount of insulin is lower than the anticipated level, which causes the sensitivity and reaction of outside butt organization （mainly skeleton muscle, liver and fat organization） to the inside source or the outside source insulin to become lower, and causes the insulin measuring for physiology to produce lower physiology effect than normal. This is a kind of abnormal pathologic physiology appearance, and is the common dangerous factor among many clinical diseases, which has become a hot issue of research interested by many academics in medical field in recent years.The insulin resistance after wound is very widespread. The states under stimulation such as serious infection, wound, surgical operation, etc. usually bring strong incitement to the organic body, causing hormone under stimulation to release in great quantities and the organization’s sensitivity to the insulin to lower via the variety of nerve endocrine, causing the mess of sugar metabolism, and leading to a high blood sugar disease, high insulin blood disease, high blood fat disease, etc. Plasma glucose’s going up, as the organic body’s reaction of protection to wound, can guarantee the plasma glucose supply for brain cell, red cell, etc. to maintain the normal cell function. But continuous increase in the plasma glucose usually produces bad results, which is mainly presented by the toxicity function that the overloads of sugar inside the cell play in non- insulin’s dependence on the cell. Normally these cells with high plasma glucose can automatically descend absorbing plasma glucose, prevent the sugar density inside the cell from being too high, and thus protect the cell function. In the surgical operation under stimulation and anoxia, some cell factors can make the cell lose this kind of function. The overloads of sugar inside the cell cause obvious increase in oxidized metabolism outcome created by the line granule body, which to certain degree will influence the expression of particular gene and create cell toxicity function.During the round surgical operation period, a chain of stimulation factors such as patients’ mental fear, anaesthetizing, surgical operation, blood loss, etc. usually result in strong stimulation to the organic body, making the metabolism of insulin holdout hormone like adrenaline and pancreas high blood sugar inside the body increase, causing the sugar to lower, glucose exploitation in the outside organizations to decrease, but theβcell secretion and the liver sugar output to promote. This will lead to the appearance of both high blood sugar disease and high insulin blood disease, making the insulin sensitivity of organizations lower, then causing the mess of the sugar fat metabolism, breaking the stability of the environment inside the organic body, making the ability of the organic body in anti-infect and anti-shock obviously drop, and having bad effects on patients’ recover from the operation.Therefore, inquiry into the outbreak mechanism of insulin resistance caused by trauma has great significance in adopting valid measures and improving patients’ metabolism condition.through observing the variety of plasma insulin sensitivity index before perianaesthesia, after operation, one day after operation and three days after operation, the research studies the relationship between the degree of insulin resistance in the round surgical operation period and that of surgical operation wound, providing the theoretical basis for the adoption of a suitable processing in the clinical round surgical operation period to lower or shorten IR time after operation. ObjectiveThough observing the variety of insulin sensitivity index before perianaesthesia and after operation, the research studies the relationship between the degree of insulin holdout and that of surgical operation wound in the round surgical operation period.Materials and Methods1. General Data60 samples who have complete data of medical history and have general and gynecology belly all numb surgical operation by selecting dates without history of diabetes, ASA I～II, whose ages are 18～80 years old with normal body temperatures, the weight is 50～85 kg （the request for the scope of whose weight is≤20% of the standard weight）, who are not obviously excrescent in various normal tests and checks before operation, who don’t have diseases in heart, lung, liver, kidney and the system of the nerve muscle, and who have no mess in sour-alkali balance and water electrolyte. Grading all cases according to POSSUM, record physiology （including 12 physiology indexes）, and the trauma degree of surgical operation （including 6 indexes: the size of the surgical operation, the number of surgical operations, the total amount of blood loss, the degree of the belly cavity pollution, malignant tumor, and the category of surgical operations）. Grading upon the trauma degree of surgical operation can be divided into 3 groups, Set I: the trauma degree of surgical operation is≤7 points; Set II :the encroaching degree of surgical operation is 8～10 points; and Set III: the trauma degree of surgical operation is >10 points.2. The agentia and equipmentIn addition to regular drugs and device of anaesthesia, others are required: Siemens ADVIA Centaur full-automatic chemical light analysis instrument （Germany）Ri Li 7170A full-automatic bio-chemical analysis instrument （Japan）Zhong Jia KDC-40 centrifugal machine with low speeds （Zhong Jia branch company of Ke Da Creation corp）3. Anaesthesia MethodAll the patients have no use of medicine before operation. Intravenous injection of midazolam 5 mg, fentanyl 5μg/kg, propofol 2～2.5 mg/kg, and vecuronium 0.1 mg/kg, to carry on anaesthesia inducement. Mechanical ventilation was started after trachea intubation, with breathing frequency 10～14 times/min, and the dampness amount 8～10 ml/kg, maintaining EtCO₂ within 30～45 mmHg. Interval injection of fentanyl and vecuronium to maintain the stability of anaesthesia.4. Monitoring MethodThe anaesthesia machine chooses to use Datex-Ohmeda S/5 Aespires （containing ISO）, and apply Datex-Ohmeda S/5 CAM tightly packed type of anaesthesia guardianship instrument to monitor the noninvasive BP, ECG, and SpO₂, recording the index of the blood dynamic mechanics, including constringency, stretching press, the average artery press, CO₂ consistency （EtCO₂） at the end of breathing, and anaesthesia medicine consistency （MAC） at the end of breathing.5. Specimen CollectionRespectively before anaesthetizing inducement （To） , after pulling out windpipe pipe when the surgical operation is over （T₁）, the first morning after operation with an empty stomach （T2）, and the third morning after operation （T3）, 5 ml of outside vein blood is collected and put into the tube respectively （BD Vacutainer SST II）, carrying on an examination in blood plasma glucose and insulin.6. Specimen Examination（1） Blood plasma glucose examination:Using method of Hexokinase to measure blood plasma glucose: 2.5 ml of vein blood is placed in a vacuum centrifugal tube. Being centrifugal at low speed （3500 turns/min） 5 min, serum is taken at the upper level, and placed in a sharp ended plastic tube for an automatic examination within 6～8 hours. The model of the instrument: Ri Li 7170A full-automatic bio-chemical analysis instrument. The try box: produced by Yi Jie Company in France, the passing number: 070102, and the normal referential scope: 4.0～6.38 mmol/L.（2） Blood plasma insulin examination:Using the method of chemiluminescence to examine blood plasma insulin: 5 ml of vein blood is placed in a vacuum centrifugal tube for 37℃water bath, and a 10 minute warm cultivation, serum is separated through a centrifugal method （3500 turns/min） 5 min, and is taken to be placed in a sharp ended plastic tube for an automatic examination. The model of the instrument: Siemens ADVIA Centaur full-automatic chemical light analysis instrument. Making reference to a value: 3.0～23.0 mU/L.7. Statistics AnalysisStatistics analysis is made by using SPSS13.0 software packages. Calculating dataare presented with （X|-）±S, counting data are examined by X², and the comparisonbetween various samples of different sets is examined by square difference analysis and non-parameter （K-W）. P<0.05 means the difference has statistic meaning.ResultThe result shows that the difference between different grading sets of surgical operation trauma degree （I, II and III sets） in age, sex, POSSUM physiology grading and BMI has no statistic meaning （P>0.05）. It can be seen from the statistic result that, 24h after surgical operation, set II averagely descends by 26.82% inΔISI, set III averagely descends by up to 39.46%, but set I descends only by 15.07%, and the difference between sets has statistic meaning （P<0.05）.ConclusionThe insulin resistance （IR） presents a positive relation with the surgical operation degree. In other words, the severer the wound is, the bigger IR is. It can be seen that IR exists just when the surgical operation is over, it reaches the peak about 24h after operation, and it will descend gradually with the recover of patients. But the severer the surgical operation wound is, the longer IR will continue.更多还原