乙酰胺联合前列地尔注射液对氟乙酰胺中毒大鼠心肌的保护作用

发布时间：2018-07-09 12:48

本文选题：心肌酶 + SOD　；参考：《吉林大学》2015年硕士论文

【摘要】：研究背景：氟乙酰胺是一种高效、剧毒，吸收性强的有机氟杀鼠剂，残效期长，无腐蚀作用。氟乙酰胺中毒起病急，病情发展迅速，常致心、脑、肺、肝、肾等多脏器损伤。因其可导致人畜的二次中毒，目前已为国家禁止生产和使用。但因其效果明显，许多商贩仍进行违法生产及出售，使得氟乙酰胺中毒事件时有发生，近年甚至有上升趋势。氟乙酰胺对心脏有明显损害，，体现在对心肌细胞及传导系统的损害，心肌损害率80%以上，可致各种心律失常，心功能衰竭，血压下降，甚至心室颤动，心功能异常是其第二位死亡原因。目前公认的中毒机制为氟乙酰胺使三羧酸循环中断，从而导致各脏器损伤，对中毒后心肌损伤的情况及治疗缺乏进一步研究。探讨氟乙酰胺中毒引起心肌损伤的情况及有效的治疗方法，对降低死亡率、改善预后有重要意义。目的：探讨大鼠氟乙酰胺中毒后心肌损伤情况，与氧化损伤的关系；乙酰胺联合前列地尔注射液对中毒大鼠心肌损伤是否具有保护作用。方法：通过灌胃方法制作氟乙酰胺中毒大鼠模型，共100只大鼠，雌雄各半，将其随机分成5组。A组为正常对照组，1ml生理盐水灌胃，并每日给予等剂量生理盐水腹腔注射。B组为氟乙酰胺染毒组，氟乙酰胺溶液按6mg/kg灌胃制作氟乙酰胺中毒模型，并每日给予等剂量生理盐水腹腔注射。C组为乙酰胺治疗组，氟乙酰胺溶液按6mg/kg灌胃制作氟乙酰胺中毒模型，染毒后1小时按2.8g/kg给予乙酰胺，日二次（Q12H）腹腔注射。D组为乙酰胺+前列地尔注射液治疗组，氟乙酰胺溶液按6mg/kg灌胃制作氟乙酰胺中毒模型，染毒后1小时按2.8g/kg给予乙酰胺，日二次（Q12H）腹腔注射，同时按10ug/kg加用前列地尔注射液，日一次腹腔注射。E组为前列地尔注射液治疗组，氟乙酰胺溶液按6mg/kg灌胃制作氟乙酰胺中毒模型，染毒后1小时按前列地尔注射液10ug/kg QD腹腔注射。在5组大鼠染毒后不同时间点（4h、1d、3d、7d）取心肌组织行HE染色观察心肌形态变化；测定血液中磷酸肌酸激酶（CK）、磷酸肌酸同工酶（CK-MB）、天门冬氨酸氨基转移酶（AST）及心肌组织中超氧化物歧化酶（SOD）、丙二醛（MDA）的含量，行统计学分析，探讨其意义。结果： HE染色提示氟乙酰胺中毒大鼠心肌损伤于1d开始出现，呈点状或局灶性变性、坏死，其周围细胞胞浆染色嗜酸性增强，伴少量炎细胞浸润；3d损伤最重，心肌细胞大片状坏死、溶解消失，大量炎细胞浸润；D组与C组7d开始出现肉芽组织；D组与C组、E组相比较，心肌损伤范围小，程度轻。心肌三酶4h开始升高，1d达到高峰，3d下降，7d基本恢复正常。D组1d时AST及CK-MB值与B组、E组相比具有统计学意义（P＜0.01），其余时间点D组心肌三酶与C组、E组相比无明显差异（P＞0.05）。氟乙酰胺中毒后心肌SOD含量降低、MDA含量升高，与对照组相比有显著差异（P＜0.01）；D组与C组、E组心肌MDA含量相比明显降低（P＜0.01）；SOD含量三组之间相比无统计学意义（P＞0.05）。结论：（1）氟乙酰胺中毒可导致心肌损伤，主要表现为心肌局灶性或片状坏死，伴有炎细胞浸润。在中毒后3d损伤最重。心肌酶1d达到高峰，7d基本恢复正常。（2）健康大鼠氟乙酰胺中毒后心肌组织中SOD含量减少，MDA含量增加，考虑心肌损伤与氧化损伤有关。（3）乙酰胺联合前列地尔注射液对大鼠氟乙酰胺中毒所致心肌损伤具有保护作用，与乙酰胺治疗组及前列地尔治疗组相比，可明显减轻心肌损伤范围及程度；缩短心肌组织修复时间;能清除氧自由基，有效降低心肌组织MDA含量，达到抗氧化损伤作用。
[Abstract]:Research background:
Fluoro acetamide is a highly effective, highly toxic and Absorbable Organic Fluorine killer, which has long residual effect and no corrosion effect. Fluoro acetamide poisoning is urgent and develops rapidly. It often causes multiple organ damage in heart, brain, lung, liver and kidney. Because it can lead to two poisoning of human and animal, it has been banned from production and use in the country. The drug traffickers still carry out illegal production and sale, making the fluoro acetamide poisoning happen and even rising in recent years. The fluoro acetamide has obvious damage to the heart, which is reflected in the damage to the cardiac myocytes and conduction system, the rate of myocardial damage is above 80%, and can cause various arrhythmia, heart failure, blood pressure drop, even ventricular fibrillation, cardiac function Abnormality is the second cause of death. The current recognized mechanism of poisoning is that fluoro acetamide interrupts the circulation of three carboxylic acids, which leads to the injury of various organs, and the lack of further study on the condition of myocardial injury after poisoning and the treatment of myocardial injury caused by fluoro acetamide poisoning, and to reduce the mortality and improve the precondition. It is of great significance.
Objective:
To investigate the relationship between myocardial injury and oxidative damage in rats after fluoroacetamide poisoning, and whether acetamide and Alprostadil Injection have protective effect on myocardial injury in rats.
Method:
A rat model of fluoro acetamide poisoning was made by gavage. A total of 100 rats were divided into 5 groups of.A groups. The rats were divided into 5 groups as normal control group, 1ml saline was given to the stomach, and.B group was given daily dose of saline as the fluoro acetamide group. The fluoro acetamide solution was injected into the stomach to make the fluoro acetamide poisoning model. A daily dose of normal saline was given to the group of.C in the group of acetamide. Fluoroacetamide was injected into the stomach to make a model of fluoroacetamide poisoning according to 6mg/kg. 1 hours after exposure to 2.8g/kg was given to acetamide. Two times (Q12H) was injected into the.D group as the acetamide + Alprostadil Injection treatment group. Fluoroacetamide solution was made by 6mg/kg to make fluorine and B. The model of amidotoxism was given to acetamide by 2.8g/kg 1 hours after exposure, two times (Q12H) intraperitoneal injection, and 10ug/kg added to Alprostadil Injection,.E group was injected into group.E once daily, and fluoroacetamide solution was injected by 6mg/kg to produce fluoroacetamide poisoning model, and 1 hours after exposure to Alprostadil Injection 10. Ug/kg QD was intraperitoneally injected. Myocardial morphologic changes were observed at different time points (4h, 1D, 3D, 7D) at different time points (4h, 1D, 3D, 7D); the content of creatine phosphate kinase (CK), creatine phosphate isozyme (CK-MB), aspartate aminotransferase (AST) and the content of MDA (MDA) in myocardial tissue were measured. Statistical analysis was used to discuss its significance.
Result:
HE staining suggested that myocardium injury in rats with fluoroacetamide poisoning began to appear in 1D, showing spot or focal degeneration, necrosis, cytosolic staining of eosinophilic cells and infiltration of a small amount of inflammatory cells in the surrounding cells; 3D injury was the heaviest, myocardial cells were necrotic, dissolution disappeared, and large number of inflammatory cells infiltrated; group D and C group 7d began to appear granulation tissue; D group; D group. Compared with group C and group E, the range of myocardial injury was small and the degree of myocardial three enzyme 4H began to rise, 1D reached its peak, 3D decreased. When 7d basically recovered the 1D of normal.D group, the value of AST and CK-MB was statistically significant compared with the E group. The remaining time points had no significant difference between the three enzymes and the group (0.05). The content of muscle SOD decreased and the content of MDA increased significantly (P < 0.01) compared with the control group (P < 0.01). The myocardial MDA content in group D and C group was significantly lower than that in group E (P < 0.01), and there was no significant difference between the three groups of SOD (P > 0.05).
Conclusion:
(1) fluoroacetamide poisoning can cause myocardial injury, mainly manifested as focal or flaky necrosis of the myocardium with inflammatory cell infiltration. After poisoning, the 3D damage is the heaviest. The myocardial enzyme 1D reaches the peak, and the 7d is basically restored to normal.
(2) in healthy rats, SOD content in myocardium decreased and MDA content increased after fluoramide poisoning.
(3) acetamide combined with Alprostadil Injection has protective effect on myocardial injury caused by fluoroacetamide poisoning in rats. Compared with acetamide group and alprostadil treatment group, it can obviously reduce the extent and degree of myocardial injury, shorten the time of myocardial repair, scavenge oxygen free radicals, reduce the MDA content of myocardial tissue, and achieve oxygen resistance. Chemical damage.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R595.4

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