论文部分内容阅读
抗胰蛋白酶是人体内的一种主要的胰蛋白酶抑制剂,抗胰蛋白酶的含量较少会引起肺气肿、呼吸窘迫综合征等多种疾病的发生,临床对药品的需求量较大,因此对重组抗胰蛋白酶的研究成为一个热点,已经将抗胰蛋白酶从原核生物如大肠杆菌(Escherichia coli)、真核生物如酵母、植物如水稻(Oryza sativa)、以及动物如山羊(Capra hircus)等表达系统中得以表达。但在应用时应当注重该重组抗胰蛋白酶的安全性。本研究将转抗胰蛋白酶基因水稻(JY150248)及其非转基因对照水稻(JY150250)分别以17.5%、35%和70%的质量比添加到基础饲料中,选取出生5周的无特定病原体级(specific pathogen free,SPF)级SD(Sprague Dawley rat)大鼠140只,雌雄各半,以体重为标准随机分成7组,实验周期为90 d。检测该转基因稻米对SD大鼠营养状况和生理指标的影响,实验期间监测动物体重和进食量,结束后分别测定各组动物的血常规、血生化等指标并解剖动物进行病理观察,计算脏体指数。实验期间各组动物生长发育良好,无中毒死亡现象,转基因水稻组与非转基因水稻对照组相比,SD大鼠的血生化、血常规、脏器系数等个别指标有统计学差异(P<0.05),但这些差异无剂量相关性,无生物学意义。本研究未发现转基因水稻JY150248对实验动物有亚慢性毒性;这一研究结果也为利用转基因手段开发抗胰蛋白酶药品奠定了科学基础。
Antitrypsin is a major trypsin inhibitor in the human body. The content of antitrypsin is less likely to cause many diseases such as emphysema and respiratory distress syndrome. Therefore, the demand for drugs in clinic is relatively large, therefore Research on recombinant antitrypsin has become a hot spot, and antitrypsin has been developed from prokaryotes such as Escherichia coli, eukaryotes such as yeast, plants such as Oryza sativa, and animals such as Capra hircus Expression system to be expressed. But in the application should pay attention to the safety of recombinant anti-trypsin. In the present study, transgenic antitrypsin-transgenic rice (JY150248) and its non-transgenic control rice (JY150250) were added to basal diet at a mass ratio of 17.5%, 35% and 70%, respectively. 140 pathophysiological pathogen free (SPF) SD rats were randomly divided into 7 groups according to body weight. The experimental period was 90 days. The effects of the transgenic rice on the nutritional status and physiological indexes of SD rats were examined. The body weight and food intake of the animals were monitored during the experiment. Blood and blood biochemical indexes of the animals in each group were measured and the pathological changes were observed. index. The growth and development of animals in each group were well developed and there was no toxic death during the experiment. Compared with the non-transgenic rice control group, the indicators of blood biochemistry, blood routine and organ coefficient of transgenic rats were significantly different (P <0.05 ), But these differences were not dose-related and had no biological significance. This study did not find that transgenic rice JY150248 had subchronic toxicity to experimental animals. The results of this study also laid the scientific foundation for the development of anti-trypsin drugs by transgenic means.