右美托咪定对骨科止血带所致缺血再灌注损伤的氧化应激和炎症因子的影响
[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.
【学位授予单位】:南方医科大学
【学位级别】:硕士
【学位授予年份】:2014
【分类号】:R614
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