高效分解尿素氮和肌酐的基因工程乳酸菌的构建及其功能研究

慢性肾衰竭是危害国民健康的常见病，其目前主要的治疗方式为透析及肾移植，而这两种治疗方式均具有不同程度的有创性及局限性，导致患者最终难以得到有效的治疗。急需探索一种经济无创的方式来早期有效地治疗慢性肾衰竭。乳酸菌是人体肠道内的正常菌群，其作为外源性蛋白表达载体在医药及食品领域也具有广泛的应用。本课题组拟采用基因工程技术，构建脲酶及肌酐水解酶的融合基因，以保加利亚乳酸杆菌作为载体对融合基因进行表达，以获取一株能高效分解尿素氮和肌酐的基因工程菌。从重组质粒的遗传稳定性及在肠道菌群间的传递、重组菌在胃肠道中的稳定性及对尿毒素的分解力等多方面来验证其功能及稳定性，如能构建成功，将为慢性肾衰竭的早期治疗提供新的思路及治疗手段。

Chronic renal failure is a common disease that endangers public health, and its main treatment is dialysis and renal transplantation.There are some invasive injury and limitations with both the two ways so that patients are hard to get effective treatment ultimately. Exploring new treatment becomes urgent. Lactic acid bacteria is normal flora in the human gut, which is widely used as exogenous protein expression vector in the field of medicine and food. Our team aims to construct a combination of urease gene and creatininase gene , and clone it to Lactobacillus bulgaricus, so that it could effectively express urease and creatininase. To investigate the genetic stability of the recombinant plasmid, the survival,adhesion and colonization force capacity, and antimicrobial activity of in the gastrointestinal tract; on the other hand, to explore the capacity of creatinine and urea nitrogen removal of the gene engineering Lactobacillus bulgaricus so that provide new ideas and early treatment to chronic renal failure.