N-乙酰半胱氨酸治疗猪药物性急性肝衰竭实验研究

发布时间：2018-06-02 14:34

本文选题：急性肝衰竭 + 猪　；参考：《郑州大学》2007年硕士论文

【摘要】： 目的：以D-氨基半乳糖诱导建立急性肝衰竭动物模型，对其应用N-乙酰半胱氨酸(N-Acetylcysteine，NAC)治疗，观察NAC治疗效果，深入研究药物的作用机制。方法：选用中国实验小型猪，雌性，12头，随机分为两组：对照组(n=6)与治疗组(n=6)。应用D-氨基半乳糖1.2g/Kg静脉注射诱导建立急性肝衰竭动物模型。治疗组给药后6小时、24小时、48小时分别给予NAC150mg/kg、50mg/kg、100mg/kg加入5％葡萄糖溶液100ml静脉滴注，其后每间隔24小时给予NAC100mg/kg加入5％葡萄糖溶液100ml静脉滴注。对照组给药后6小时、24小时及其后每隔24小时分别静脉滴注5％葡萄糖溶液100ml。观察比较两组动物一般状况、生存时间、生理生化指标、颅内压、组织病理变化及血清学相关因子变化。结果：对照组动物平均存活时间为64.7±8.7小时，均死于严重肝衰竭。治疗组存活时间为66.2±10.6小时，两组平均存活时间比较，差异无显著性意义(P=0.73，P＞0.05)。与对照组相比，治疗组多项生化指标、颅内压、炎性细胞因子等都有不同程度改善(p＜0.05～p＜0.01)。病理学检查中治疗组除60小时组外，其余时间点组织病理示较对照组有较好的恢复。免疫组化检查中，对照组PCNA存在阳性表达，但数量较少，着色浅；治疗组阳性表达数量多，着色相对较深。两组阳性细胞计数后经统计学分析，两组阳性表达率的差异有显著性意义(p＜0.05)；对照组和治疗组中均有Caspase-3阳性表达，细胞质和细胞核均着棕黄色颗粒状，疏密不等，但治疗组的阳性颗粒数少于对照组。结论：NAC应用于急性肝功衰竭治疗具有一定的疗效：①NAC治疗可以改善机体的一般状况和机能，在一定程度上为肝脏功能的恢复提供有益的帮助。②NAC治疗可以减少体内TNF-a、IL-1β炎症细胞因子的生成，抑制炎症反应的快速发展，稳定机体的内环境，减轻肝脏损伤，为肝细胞的再生、修复提供条件；③NAC治疗对维持氧化和抗氧化的平衡发挥一定的作用，可以通过增加抗氧化剂SOD、还原性谷胱甘肽和一氧化氮的含量来清除肝脏内氧化剂产生的氧自由基，减少氧自由基对肝脏的损伤，，起到保护肝脏的作用；④NAC可以促进肝细胞的再生，有利于肝脏的功能恢复。综上所述，N-乙酰半胱氨酸的应用为肝功能衰竭的临床治疗提供了一种有效的方法和新的选择，具有重要的临床意义。
[Abstract]:Aim: to establish an animal model of acute hepatic failure induced by D-galactosamine (D-galactosamine) and to observe the effect of N-Acetylcysteine NAC-1 (N-Acetylcysteine NAC-1) in the treatment of acute hepatic failure. Methods: twelve Chinese experimental miniature pigs were randomly divided into two groups: control group (n = 6) and treatment group (n = 6). Acute hepatic failure model was established by intravenous injection of D-galactosamine 1.2g/Kg. In the treatment group, NAC 150 mg 路kg ~ (-1) 50 mg 路kg ~ (-1) ~ (100 mg / kg) added 5% glucose solution (100ml) was given intravenously at 6 hours and 24 hours after administration respectively, and then NAC100mg/kg was injected intravenously with 5% glucose solution 100ml every 24 hours thereafter. In the control group, 5% glucose solution was injected intravenously for 24 hours 6 hours after administration and every 24 hours thereafter. The changes of general condition, survival time, physiological and biochemical indexes, intracranial pressure, histopathological changes and serological related factors were observed and compared between the two groups. Results: the average survival time of the control group was 64.7 卤8.7 hours, all of them died of severe liver failure. The survival time of the treatment group was 66.2 卤10.6 hours. There was no significant difference in the mean survival time between the two groups (P > 0.05). Compared with the control group, many biochemical indexes, intracranial pressure and inflammatory cytokines in the treatment group were improved to some extent (p < 0.05) and P < 0.01 (P < 0.01). In pathological examination, the histopathology of treatment group was better than that of control group except 60 hours group. In the immunohistochemical examination, the positive expression of PCNA was found in the control group, but the number was less and the staining was shallow, while in the treatment group, the number of positive expression was more and the staining was relatively deep. After counting the positive cells in the two groups, the difference of the positive expression rate between the two groups was significant (p < 0.05), the positive expression of Caspase-3 was found in both the control group and the treatment group, the cytoplasm and nucleus were brown granular, and the density was different. But the number of positive granules in the treatment group was less than that in the control group. Conclusion the application of WN NAC in the treatment of acute hepatic failure has a certain curative effect: 1 NAC can improve the general condition and function of the body. To a certain extent, NAC therapy can reduce the production of inflammatory cytokines, inhibit the rapid development of inflammatory response, stabilize the internal environment of the body, and alleviate liver injury. The treatment of NAC for the regeneration and repair of hepatocytes plays a certain role in maintaining the balance of oxidation and antioxidation. By increasing the contents of antioxidant SOD, reductive glutathione and nitric oxide, the oxygen free radicals produced by oxidants in the liver can be eliminated, the damage of oxygen free radicals to the liver can be reduced and the liver can be protected. 4NAC can promote the regeneration of hepatocytes and facilitate the recovery of liver function. To sum up, the application of N-acetylcysteine provides an effective method and a new choice for the clinical treatment of liver failure, and has important clinical significance.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2007
【分类号】：R575.3;R-332

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