【摘要】：機(jī)體組織器官正常代謝、功能的維持,有賴于良好的血液循環(huán)。各種原因造成的局部組織器官的缺血,常常使組織細(xì)胞發(fā)生缺血性損傷,但在動物試驗和臨床觀察中也發(fā)現(xiàn),在一定條件下恢復(fù)血液再灌注后,部分動物或患者細(xì)胞功能代謝障礙及結(jié)構(gòu)破壞不但未減輕反而加重,因而將這種血液再灌注后缺血性損傷進(jìn)一步加重的現(xiàn)象稱為缺血再灌注損傷(ischemia-reperfusion injury IRI)。臨床上骨科止血帶多用于肢體手術(shù)以達(dá)到減少術(shù)中失血和保持術(shù)野清晰的目的,然而骨科止血帶所引發(fā)的IRI損傷不但可以造成肢體原發(fā)部位的損傷：輕者表現(xiàn)為肌肉晚期纖維化、攣縮、影響功能；重者可致肢體壞死。而且還可以引起繼發(fā)遠(yuǎn)隔器官的損傷,特別是側(cè)支循環(huán)不豐富,且需氧量高的的器官,如肝、腦、心等。在缺血時間過長,再灌注條件不理想的情況下如高壓、高溫、高鈉、高鈣灌注更易引起組織器官的損傷。骨科止血帶所致IRI的機(jī)制主要是通過以下兩種途徑實現(xiàn)的,一方面是由于氧自由基引發(fā)的脂質(zhì)過氧化作用,使機(jī)體的氧化應(yīng)激水平升高。另一方面是中性粒細(xì)胞在炎癥因子參與下介導(dǎo)的炎癥反應(yīng)。氧化應(yīng)激反應(yīng)是指機(jī)體在遭受各種有害刺激時,體內(nèi)高活性分子如活性氧自由基氧化程度超出氧化物的清除能力,氧化系統(tǒng)和抗氧化系統(tǒng)失衡,從而導(dǎo)致組織損傷的一種情況。氧自由基主要通過脂質(zhì)過氧化作用損傷細(xì)胞,氧自由基可與生物大分子特別是細(xì)胞膜上的不飽和脂肪酸反應(yīng),形成脂質(zhì)過氧化物,破壞物膜。脂質(zhì)過氧化物降解形成內(nèi)二醇(malondialdehyde MDA), MDA可使)NA、蛋白質(zhì)發(fā)生交聯(lián)和聚合,當(dāng)DNA雙股螺旋都發(fā)生交聯(lián)時,細(xì)胞分裂時雙股螺旋就不能解開,從而導(dǎo)致細(xì)胞變性死亡；蛋白質(zhì)的變性可以就引發(fā)酶活性發(fā)生改變,影響物質(zhì)代謝；MDA還可以影響線粒體呼吸鏈復(fù)合物和關(guān)鍵酶的活性使細(xì)胞能量代謝紊亂。細(xì)胞膜的脂質(zhì)過氧化作用可以細(xì)胞通透性增加,線粒體腫脹,溶酶體釋放,從而導(dǎo)致細(xì)胞的變性壞死。而清除氧自由基的酶類主要是超氧化物歧化酶(superoxide dismutase SOD),SOD的減少,使再灌注損傷更為嚴(yán)重。炎癥因子介導(dǎo)中性粒細(xì)胞形成“呼吸爆發(fā)”從而引發(fā)再灌注局部組織和遠(yuǎn)隔器官功能障礙。骨科止血帶所引發(fā)的IRI過程中,腫瘤壞死因子-α[(tumor necrosisfactor-α TNF-α)是最早出現(xiàn)、最敏感的炎癥因子之一,而目前認(rèn)為由TNF-α、白介素-1(interleukin-1IL-1)、白介素-6(interleukin-6IL-6)誘發(fā)的炎癥反應(yīng)在很大程度上是通過誘導(dǎo)產(chǎn)生白介素-8(interleukin-8IL-8)為代表的趨化因子所介導(dǎo)的,IL-8在炎癥反應(yīng)中起更直接的介導(dǎo)作用。怎樣預(yù)防和處理骨科止血帶所引發(fā)的IRI,減少術(shù)后并發(fā)癥和死亡率一直是困擾麻醉醫(yī)生和骨科醫(yī)生的常見問題之一。近幾年來缺血預(yù)處理作為一種有效的預(yù)防手段越來越得到大家重視,所謂缺血預(yù)處理(Ischemia preconditioning IPC)是一種能夠通過觸發(fā)機(jī)體組織的內(nèi)源性的保護(hù)機(jī)制而起到抗IRI的方法。目前IPC作為一種最有效的內(nèi)源性保護(hù)機(jī)制越來越受到大家的關(guān)注,但其畢竟會對機(jī)體造成傷害,而且具有一定的不確定性,主要表現(xiàn)在對實施IPC的最佳時間和次數(shù)、患者的個體差異等問題難以準(zhǔn)確監(jiān)測和評估。因此人們根據(jù)IPC的機(jī)理提出了一種既不損傷器官又能產(chǎn)生預(yù)適應(yīng)效果的的方法—藥物預(yù)處理(pharmacologic preconditioningPPC)。已有實驗證明,多種藥物可以起到PPC的效果,如嗎啡,七氟醚,異丙酚,甘露醇,肝素等。右美托咪定(dexmedetomidine,DEX)是新一代的高選擇性的α2腎上腺素受體激動劑。DEX作用廣泛,因其具有鎮(zhèn)靜催眠、抗驚厥、抗焦慮、穩(wěn)定血流動力學(xué)的作用已被廣泛用于輔助檢查及門診短小手術(shù)及ICU鎮(zhèn)靜。同時由于DEX可降低麻醉誘導(dǎo)期插管時機(jī)體應(yīng)激反應(yīng)及減少麻醉劑與阿片類藥物的用量,改善術(shù)后患者對氣管導(dǎo)管的耐受性,降低患者術(shù)后煩躁和譫妄發(fā)生率等一系列優(yōu)勢被廣泛應(yīng)用于手術(shù)室麻醉。除以上作用外,隨著對DEX的深入研究,有研究者證實DEX對機(jī)體許多重要臟器如心、腦、肝、腎等IRI具有保護(hù)作用。而有關(guān)右美托咪定預(yù)處理對骨科止血帶所致IRI的保護(hù)作用的報道還比較少。 目的 觀察右美托咪定對骨科止血帶所致IRI氧化應(yīng)激和炎癥因子的影響 材料和方法 1病例選擇與分組 隨機(jī)選取南方醫(yī)科大學(xué)附屬南方醫(yī)院創(chuàng)傷骨科和關(guān)節(jié)骨科擇期行下肢手術(shù)患者80例,分為2組,其中對照組40例,右美托咪定組(DEX組)40例�；颊呷脒x標(biāo)準(zhǔn)如下：無椎管內(nèi)麻醉禁忌癥；ASA分級Ⅰ-Ⅱ,術(shù)前心功能Ⅰ-Ⅱ級,EF55%；肝、肺、腎功能正常；無風(fēng)濕活動指征；無糖尿病,無神經(jīng)系統(tǒng)、精神疾病史及免疫系統(tǒng)病史；無結(jié)核、肝炎、梅毒、艾滋病等傳染性疾病。研究對象均為漢族,無親緣關(guān)系,兩組性別、年齡、體重指數(shù)和止血帶應(yīng)用時間差異無統(tǒng)計學(xué)意義(P0.05)。 2麻醉方法 患者術(shù)前常規(guī)禁食、禁飲,進(jìn)入手術(shù)室后,給予鼻導(dǎo)管2L/min吸氧,及時開放外周靜脈通路,監(jiān)測心電圖(ECG),脈搏血氧飽和度(Sp02),無創(chuàng)血壓(NIBP)和心率(HR)。所有患者均采用兩點(diǎn)穿刺腰硬聯(lián)合麻醉,感覺平面固定在T10以下,20G留置針對患肢行股靜脈穿刺術(shù)并固定留置針,肝素封管備用�；贾蚪亩蓑�(qū)血后在大腿中上1/3處放置止血帶,止血帶的壓力設(shè)置為術(shù)前收縮壓加100mmHg,時間設(shè)定為60min。術(shù)中選用復(fù)方氯化鈉注射液作為補(bǔ)充液體,其給予量按10ml·kg-1·h-1輸注。當(dāng)患者出現(xiàn)血壓低于85mmHg或血壓下降為基礎(chǔ)值的20%時可給予麻黃堿5mg/次,當(dāng)患者心率低于50次／分時,根據(jù)情況可酌情給予阿托品0.25mg／次,當(dāng)患者Sp0295%時可改用面罩輔助通氣。 3右美托咪定給藥方法 DEX組靜脈給予DEX負(fù)荷劑量1μg/kg (10min內(nèi)輸注完畢),10min后改為維持劑量0.5μg/kg/h至手術(shù)結(jié)束。對照組給予等速度等容量的生理鹽水。 4標(biāo)本處理及檢測 分別于T1(上止血帶前),T2(松止血帶后10min),T3(松止血帶后30min),T4(松止血帶后60min)共4個時間點(diǎn)抽取手術(shù)側(cè)股靜脈血5ml,裝入試管中,以3000轉(zhuǎn)/min的轉(zhuǎn)速離心5min后低溫(-20℃)保存,一周內(nèi)按ELISA試劑盒方法檢測MDA、SOD、TNF-α和IL-8的含量。5統(tǒng)計學(xué)處理 所有計量資料均以均數(shù)±標(biāo)準(zhǔn)差(x±s)表示,兩組均數(shù)比較采用獨(dú)立樣本t檢驗；多個樣本均數(shù)組間比較采用重復(fù)測量的方差分析,計數(shù)資料比較采用χ2檢驗。P0.05認(rèn)為差異有統(tǒng)計學(xué)意義。資料數(shù)據(jù)的統(tǒng)計應(yīng)用SPSS19.0(Statistical Package for the Social Science)軟件包完成。 結(jié)果 1兩組病人不同時間點(diǎn)的生命體征情況 兩組患者4個時間點(diǎn)NIBP、HR、SpO2組間比較差異無統(tǒng)計學(xué)意義(P0.05),兩組患者NIBP、HR、SpO2組內(nèi)比較差異無統(tǒng)計學(xué)意義(P0.05)。 2兩組病人不同時間點(diǎn)氧化應(yīng)激標(biāo)志物MDA的變化 在T1時間點(diǎn),兩組患者血清MDA含量無顯著性差異(P0.05)。松止血帶后,與T1時間點(diǎn)相比,T2、T3和T4時間點(diǎn)對照組和DEX組患者股靜脈血清MDA含量顯著升高(P0.05)。但DEX組患者在T2、T3和T4時間點(diǎn)的血清MDA含量顯著低于對照組(P0.05)。3兩組病人不同時間點(diǎn)氧化應(yīng)激標(biāo)志物SOD的變化 在T1時間點(diǎn),兩組患者血清SOD含量無顯著性差異(P0.05)。松止血帶后,與T1時間點(diǎn)相比,T2、T3和T4時間點(diǎn)對照組和DEX組患者股靜脈血清SOD含量顯著降低(P0.05)。但DEX組患者在T2、T3和T4時間點(diǎn)的血清SOD含量顯著高于對照組(P0.05)。 4兩組病人不同時間點(diǎn)炎性因子TNF-a的變化 在T1時間點(diǎn),兩組患者血清TNF-α含量無顯著性差異(P0.05)。松止血帶后,與T1時間點(diǎn)相比,T2、T3和T4時間點(diǎn)兩組患者血清TNF-a含量均顯著升高(P0.05)。與對照組相比,DEX組患者在T2、T3和T4時間點(diǎn)的血清TNF-α含量顯著降低(P0.05) 5兩組病人不同時間點(diǎn)炎性因子IL-8的變化 在T1時間點(diǎn),兩組患者血清IL-8含量無顯著性差異(P0.05)。松止血帶后,與T1時間點(diǎn)相比,T2、T3和T4時間點(diǎn)兩組患者血清IL-8含量均顯著升高(P0.05)。與對照組相比,DEX組患者在T2、T3和T4時間點(diǎn)的血清IL-8含量顯著降低(P0.05)。 結(jié)論 右美托咪定可顯著降低骨科止血帶所致IRI引起的氧化應(yīng)激和炎癥因子水平的增高。
[Abstract]:Normal metabolism and maintenance of function of tissues and organs depend on good blood circulation. Ischemia of local tissues and organs caused by various causes often causes ischemic injury of tissue and cells. However, in animal experiments and clinical observations, it is also found that under certain conditions, after recovery of blood reperfusion, the functional metabolism of some animals or patients is restored. Obstacles and structural damage are not alleviated but aggravated, and this further aggravation of ischemic injury after reperfusion is called ischemia-reperfusion injury (IRI). The injury of IRI caused by tourniquet can not only cause the injury of the primary part of limb, but also cause the injury of distal organs, especially those organs with low collateral circulation and high oxygen demand, such as liver, brain and heart. Orthopedic tourniquet-induced IRI is mainly achieved by two ways. On the one hand, it is caused by lipid peroxidation induced by oxygen free radicals, which increases the level of oxidative stress. Oxidative stress is a condition in which highly active molecules such as reactive oxygen species (ROS) are oxidized beyond the scavenging capacity of oxides, and the oxidative and antioxidant systems are imbalanced, leading to tissue damage when the body is subjected to various harmful stimuli. Cells are damaged mainly by lipid peroxidation. Oxygen radicals can react with biomolecules, especially unsaturated fatty acids on cell membranes, to form lipid peroxides and destroy membrane. Lipid peroxides degrade to form endodiol (malondialdehyde MDA), MDA can make) NA, and proteins cross-link and polymerize when DNA double helix is present. When cross-linking occurs, the double helix can not be disentangled during cell division, leading to cell degeneration and death; protein denaturation can lead to changes in enzyme activity, affecting substance metabolism; MDA can also affect the activities of mitochondrial respiratory chain complexes and key enzymes, resulting in energy metabolism disorders. The main enzymes scavenging oxygen free radicals are superoxide dismutase (SOD) and the decrease of SOD, which make the reperfusion injury more serious. Inflammatory factors mediate the formation of "respiratory burst" of neutrophils leading to reperfusion. Tumor necrosis factor-alpha (TNF-alpha) is one of the earliest and most sensitive inflammatory factors in the process of IRI induced by orthopaedic tourniquet. At present, TNF-alpha, interleukin-1 (IL-1) and interleukin-6 (IL-6) are considered to be the most sensitive inflammatory factors. Interleukin-8 (IL-8) plays a more direct role in mediating inflammation by inducing the production of chemokines such as interleukin-8 (IL-8). How to prevent and treat IRI caused by orthopaedic tourniquets and reduce postoperative complications and mortality has been a common problem for anesthesiologists and orthopedists. In recent years, ischemic preconditioning (IPC) has attracted more and more attention as an effective preventive measure. The so-called ischemic preconditioning (IPC) is a method that can resist IRI by triggering the endogenous protective mechanism of organism tissues. People are concerned, but after all, it will do harm to the body, and has certain uncertainty, mainly in the implementation of IPC in the best time and frequency, individual differences between patients and other issues difficult to accurately monitor and assess. Drug preconditioning (PPC). It has been shown that a variety of drugs can play a role in PPC, such as morphine, sevoflurane, propofol, mannitol, heparin, etc. Anti-convulsion, anti-anxiety and hemodynamic stabilization have been extensively used in adjuvant examinations, short-term outpatient surgery and ICU sedation. DEX can also reduce stress response during anesthesia induction, reduce the dosage of anesthetics and opioids, improve the patient's tolerance to tracheal catheters, and reduce postoperative irritability and irritability. A series of advantages, such as the incidence of delirium, have been widely used in operating room anesthesia. In addition to these effects, with the in-depth study of DEX, some researchers have confirmed that DEX has protective effects on many important organs such as heart, brain, liver and kidney. The protective effects of dexmedetomidine preconditioning on IRI caused by orthopedic tourniquet are also compared. Less.
objective
To observe the effect of dexmedetomidine on IRI oxidative stress and inflammatory factors in Department of orthopedics tourniquet
Materials and methods
1 case selection and grouping
Eighty patients who underwent selective lower limb surgery in the Department of Traumatic Orthopaedics and Arthroplasty of Southern Hospital Affiliated to Southern Medical University were randomly selected and divided into two groups, 40 in the control group and 40 in the dexmedetomidine group (DEX group). Normal; No indication of rheumatic activity; No diabetes mellitus, no history of nervous system, mental illness and immune system disease; No tuberculosis, hepatitis, syphilis, AIDS and other infectious diseases. The subjects were all Han nationality, unrelated. There was no significant difference in gender, age, body mass index and tourniquet application time between the two groups (P 0.05).
2 anesthesia methods
Patients were given oxygen inhalation through nasal catheter for 2 L/min after entering the operating room. Peripheral venous access was opened in time. Electrocardiogram (ECG), pulse oxygen saturation (Sp02), noninvasive blood pressure (NIBP) and heart rate (HR) were monitored. The pressure of the tourniquet was set as preoperative systolic blood pressure plus 100 mmHg for 60 minutes. Compound sodium chloride injection was used as a supplementary fluid during the operation. The dosage was infused at 10 ml kg 1 h 1. Ephedrine was given 5 mg/time when the blood pressure was below 85 mmHg or 20% of the baseline. Atropine was given 0.25 mg/time when the heart rate was below 50 beats/minute, and mask-assisted ventilation was used when Sp0295%.
3 dexmedetomidine administration
In DEX group, the loading dose of DEX was 1 ug/kg (10 minutes after infusion), and the maintenance dose was 0.5 ug/kg/h after 10 minutes until the end of operation.
4 sample handling and testing
The femoral vein blood samples were collected at T1 (before the tourniquet), T2 (10 minutes after the tourniquet loosening), T3 (30 minutes after the tourniquet loosening), T4 (60 minutes after the tourniquet loosening). The blood samples were stored in a test tube at a rotating speed of 3000 rpm for 5 minutes at a low temperature (-20 C). The contents of MDA, SOD, TNF-alpha and IL-8 were detected by ELISA kit within one week. Study treatment
All measurements were expressed as mean [standard deviation] (x [s], and the mean comparisons between the two groups were performed by independent sample t test; multiple sample mean comparisons were performed by repeated measurements of variance analysis; and the count data were compared by_2 test. P 0.05 showed that the difference was statistically significant. Ocial Science) the software package is completed.
Result
1 vital signs of two groups of patients at different time points.
There was no significant difference in NIBP, HR and SpO2 between the two groups at 4 time points (P 0.05). There was no significant difference in NIBP, HR and SpO2 between the two groups (P 0.05).
2 Changes of oxidative stress marker MDA in two groups of patients at different time points
There was no significant difference in serum MDA levels between the two groups at T1 time point (P 0.05). After loosening tourniquet, the serum MDA levels in the control group and the DEX group at T2, T 3 and T4 time points were significantly higher than those at T1 time point (P 0.05). However, the serum MDA levels in the DEX group at T2, T 3 and T4 time points were significantly lower than those in the control group (P 0.05). Changes of marker SOD in point of oxidative stress
There was no significant difference in serum SOD levels between the two groups at T1 time point (P 0.05). After relaxation of tourniquet, the serum SOD levels in femoral vein of the control group and the DEX group at T2, T3 and T4 time points were significantly lower than those of the control group (P 0.05).
4 the change of inflammatory factor TNF-a in two groups of patients at different time points
There was no significant difference in serum TNF-a between the two groups at T1 time point (P 0.05). After loosening tourniquet, the serum TNF-a levels of the two groups at T2, T3 and T4 time points were significantly higher than those at T1 time point (P 0.05). Compared with the control group, the serum TNF-a levels of the DEX group at T2, T3 and T4 time points were significantly lower (P 0.05).
5 the change of inflammatory factor IL-8 in two groups of patients at different time points
There was no significant difference in serum IL-8 between the two groups at T1 time point (P 0.05). After loosening tourniquet, the serum IL-8 levels of the two groups at T2, T3 and T4 time points were significantly higher than those at T1 time point (P 0.05). Compared with the control group, the serum IL-8 levels of the DEX group at T2, T3 and T4 time points were significantly lower (P 0.05).
conclusion
Dexmedetomidine significantly decreased oxidative stress and inflammatory factors induced by IRI in patients with orthopedic tourniquet.
【學(xué)位授予單位】：南方醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R614

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相關(guān)期刊論文 前10條

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