壳聚糖季铵盐与线粒体相互作用的生物热动力学及其机理

Chitosan quaternary ammonium salt was regarded as biomedical carrier with application because of its good water-solubility, high cationic potential, and strong cell adhesion. In addition, it was the research hotspots of genetic vecter in recent years. In this project, chitosan quaternary ammonium salt will be taken as the main system, and lots of research techniques, such as microcalorimetry, microscopy, spectroscopy, flow cytometry, enzyme link immunosorbent assayed (ELISA) etc. will be combined. With the help of thermokinetics, the biological effect and mechanism of chitosan quaternary ammonium salt on mitochondria will be investigated from structure and function on the level of subcellar organelle. The effect of molecular weight and degree of substitution of chitosan quaternary ammonium salt will be further explored. The thermokinetic model of the effect of chitosan quaternary ammonium salt on living metabolism will be established, and a lot of thermokinetic parameters will be obtained. The biological effect mechanism of chitosan quaternary ammonium salt , and the relationship between its stucture and thermokinetic properties, will be revealed. The study will provide a lot of important information on synthesis, application and biosafety eveluation of chitosan quaternary ammonium salt .

壳聚糖季铵盐因其水溶性好、带正电性强、细胞黏附性好，而成为具有应用价值的生物医用载体，也是近年来基因载体材料的研究热点之一。本项目拟在亚细胞水平上，以线粒体作为主要研究对象，采用微量热、呼吸耗氧等方法，建立壳聚糖季铵盐与线粒体相互作用的热动力学模型，获取相关的热动力学信息。采用光谱法、显微分析、流式细胞术、酶联免疫等多种先进技术手段相结合，研究壳聚糖季铵盐对线粒体形态、呼吸功能、膜渗透性转换、细胞色素c、活性氧等的影响，并进一步考察分子量、取代度对壳聚糖季铵盐与线粒体相互作用影响的规律性，揭示内在作用机理。该研究旨在深入了解壳聚糖季铵盐在生命体内的动态代谢过程中的影响途径和作用机制，为壳聚糖季铵盐作为医用载体的安全性，提供亚细胞水平的理论和实践依据，同时促进学科深层次的交叉渗透。

采用微量热、显微、光谱和生化分析等技术，结合热动力学方法，在亚细胞的水平上，从结构和功能方面研究了壳聚糖季铵盐（HACC）对动物线粒体代谢动态过程的影响及其机制。建立了线粒体代谢过程热动力学模型，获取了HACC对线粒体代谢动态过程影响的热动力学特征；采用显微技术，观察了线粒体形态和结构的动态变化；研究了线粒体膜渗透性转换（MPTP）、H+/K+渗透性和呼吸耗氧的变化规律；探讨了HACC经体外途径对线粒体代谢的影响。从线粒体层面深化了对HACC生物效应机制的认识，从宏观到微观建立了HACC生物效应研究的新方法，为指导HACC的安全利用，提供了理论依据。. 项目执行期间，相关研究工作在国内外刊物上发表了论文3篇，获得国家发明专利4项，另有1篇SCI源刊论文已被接收，较好的完成了该项目的研究任务。