体外检测药疹患者致敏药物的动物实验

发布时间：2018-05-21 08:35

本文选题：药疹 + 致敏药物　；参考：《河北医科大学》2010年硕士论文

【摘要】： 目的:药物通过注射内服吸入等途径进入人体后引起的皮肤粘膜反应称为药疹。药物引起的不良反应非常复杂,大致可以分药物过量不耐受性特发性副作用继发作用及过敏反应等,药疹是过敏反应最常见的类型。在临床上应用多种药物进行治疗的病人发生药物过敏,当这种病人不能停药时,可以通过动物实验来检测此种病人对何种药物过敏,从而停止该药物,而不停用其他药物,从而不延误病人的治疗。但药疹的实验分为皮肤实验和实验室试验,两者都不完善。本实验就是通过已明确何种药物致敏的患者的血清注射到动物局部,通过注射后引起的全身反应和局部反应为动物实验检测药疹患者致敏药物提供参考。本实验所用动物是小鼠,通过小鼠局部注射后引起的全身反应和局部反应来完成本实验,为临床提供参考以克服传统激发试验所带来的危险性。方法:本实验是通过药疹患者的血清注入小鼠背部局部皮下,24,48小时后局部注入药疹患者的致敏药物,试验组小鼠出现全身反应和局部反应的阳性率较高,而对照组阳性率较低。通过试验组和对照组比较来为动物实验检测药疹患者何种药物致敏提供参考。药疹患者15例均来自河北医科大学第三医院皮肤科,时间是2009年3月到2009年12月。这些药疹患者均经过详细询问用药史,并且反复发生该药物过敏。其中有5例是来自其他科室用药过程中发生过敏并且激发试验也证明对此药过敏。其中有2例司帕沙星过敏,2例左氧氟沙星过敏,1例二甲双呱过敏,1例青霉素类过敏,1例磺胺药物过敏,8例解热镇痛药过敏。小鼠均来自河北医科大学动物实验中心,小鼠随机分组进行背部局部皮下注射,对照组是采用药疹患者血清注入小鼠背部局部皮下,24,48小时后局部再注射生理盐水。观察局部反应和全身反应,进行对照组和试验组对比。试验组和对照组均取局部组织进行普通HE染色,再进行镜检。最后对局部反应和全身反应进行评分。过敏反应症状:0正常,1躁动,2竖毛,3颤抖,4搔鼻,5喷嚏,6咳嗽,7呼吸急促,8排尿,9排粪,10流泪,11呼吸困难,12哮鸣音,13紫癜,14步态不稳,15跳跃,16喘息,17痉挛,18旋转,19潮式呼吸,20死亡。全身反应评价标准:过敏反应阴性(-) 0分;弱阳性(+) 1-4分;阳性(++) 5-10分;强阳性(+++) 11-19分;极强阳性(++++) 20分本次实验用90只小鼠进行试验,每次6只,每次分2组,每组3只,分对照组和试验组,小鼠自由分配。共进行15次试验。结果:试验组阳性率较高,甚至有小鼠出现死亡的极强阳性的表现,而对照组阳性率较低。试验组阳性例数:7例躁动,3例呼吸急促,4例颤抖,4例排尿粪,6例步态不稳,5例旋转,2例喷嚏,2例死亡。试验组阴性例数:12例。对照组阳性例数:1例躁动,1例旋转,1例颤抖,2例呼吸困难。对照组阴性例数:40例。结论:药疹病人血清注入小鼠背部局部皮下,24,48小时后再注入生理盐水,这对照组45例中5例阳性变化,病理无变化,而试验组为小鼠背部局部皮下注入药疹患者血清,24,48小时后再注入药疹患者致敏药物,这试验组45例中有33例阳性变化,病理有大量的炎细胞。通过试验组和对照组的比较,由于n40且所有T5(T为理论数,n为例数)用普通卡方检验P0.01有统计学意义,说明试验组和对照组出现差别,试验组阳性率高于对照组。临床上如果怀疑某患者对某药过敏,可以通过药疹患者血清注入小鼠背部局部皮下,24,48小时后再注入怀疑的致敏药物,如果出现过敏反应症状并且阳性率较高,,病理出现大量炎细胞,则该患者可能对该药过敏,可以停用该药物。
[Abstract]:Objective: drug rash is called drug rash caused by drug injection, inhalation and so on. The adverse reactions caused by drugs are very complex, generally can be divided into drug overdoses, intolerance, side effects, secondary and anaphylaxis, and drug rash is the most common type of anaphylaxis. A variety of clinical applications are used in clinical practice. Drugs for the treatment of patients with drug allergy, when the patient can not stop drugs, can be tested by animal experiments to determine the patient's drug allergy, and then stop the drug, without stopping the use of other drugs, and not delay the patient's treatment. But the drug rash experiment is divided into skin tests and laboratory tests, both are imperfect. The experiment is to provide a reference for the detection of allergic drugs in patients with drug eruptions by injecting the serum of the patients with specific drug sensitization to the animal's part, through the systemic and local reactions after the injection. The animals used in this experiment are completed by the systemic and local reactions caused by the local injection of the mice. This experiment provides a reference for clinic to overcome the danger of traditional stimulation test.
Methods: this experiment was injected into the local subcutaneous of the back of the mice by the serum of the drug eruption patients, and the sensitized drugs were injected locally after 24,48 hours. The positive rate of the whole body reaction and the local reaction in the experimental group was higher, and the positive rate of the control group was low. 15 cases of drug eruptions were from the Department of dermatology at the Third Hospital of Hebei Medical University from March 2009 to December 2009. The drug rash patients were all inquired about the history of drug use and repeated the drug allergy. Of these, 5 were allergic and provocative tests from other departments. There were 2 cases of sparfloxacin allergy, 2 cases of levofloxacin allergy, 1 cases of two a double croak, 1 cases of penicillin allergy, 1 case of sulfanilamide allergy, and 8 cases of antipyretic and analgesic drug allergy. All of the mice were from the Hebei Medical University animal experiment center, the mice were randomly divided into subcutaneous injection in the back, and the control group was used drug rash. The patient's serum was injected into the subcutaneous part of the mouse's back, and the saline was injected locally after 24,48 hours. The local reaction and the whole body reaction were observed. The control group and the control group were compared with the experimental group. The experimental group and the control group were taken local tissue for general HE staining, and then the microscopic examination was performed. Finally, the local reaction and the whole body reaction were evaluated.
Allergic reaction symptoms: 0 normal, 1 restlessness, 2 erect hair, 3 tremors, 4 scratches, 5 sneezes, 6 coughs, 7 breaths, 8 urination, 9 dung, 10 tears, 11 breathing difficulties, 12 wheezing, 13 purpura, unstable gait, wheezing, spastic spasm, tidal breathing, death.
The general reaction evaluation criteria: allergic reaction negative (-) 0 points; weak positive (+) 1-4 points; positive (+ +) 5-10 points; strong positive (+ + +) 11-19 points; extremely strong (+ + + +) 20 points.
In this experiment, 90 mice were tested, 6 each time, each time was divided into 2 groups, each group 3, divided into the control group and the experimental group, the mice were allocated freely. Altogether 15 tests were carried out.
Results: the positive rate of the test group was higher, and even the death rate of the mice was very strong, while the positive rate of the control group was low.
The number of positive cases in the test group: 7 cases of restlessness, 3 cases of shortness of breath, 4 cases of trembling, 4 cases of urination, 6 cases of gait instability, 5 cases of rotation, 2 cases of sneezing, 2 cases of death. The number of negative cases in the test group: 12 cases.
Control group positive cases: 1 cases of restlessness, 1 cases of rotation, 1 cases of tremor, 2 cases of dyspnea. Control group negative cases: 40 cases.
Conclusion: the sera of the patients with drug eruption were injected into the subcutaneous part of the mouse's back, and then injected with saline after 24,48 hours. There were 5 positive changes in the 45 cases of the control group, and the pathological changes were not changed. The experimental group injected the serums of the local subcutaneous injection of drug eruptions in the mice back, and then the drug erupted after 24,48 hours, and there were 33 positive changes in the test group of 45 cases. There was a large number of inflammatory cells in the pathology. Through the comparison between the experimental group and the control group, the test group was significantly higher than the control group because of N40 and all T5 (T theory number, n as the number of cases) with ordinary chi square test, indicating the difference between the test group and the control group, and the positive rate of the test group was higher than that of the control group. When the serum is injected into the subcutaneous part of the mouse's back, the suspected sensitizing drug is injected after 24,48 hours. If the allergic reaction is found and the positive rate is high, a large number of inflammatory cells are found in the pathology, then the patient may be allergic to the drug, and the drug can be discontinued.
【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R758.25

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