Using C. Elegans As A Model Organism To Study The Injury Mechanism Of Different Environmental Factors And Developing The Protective Strategies

Stable living environment is very important to organism of normal growth, development and reproduction. In evolutionary process, organisms always adapt to environment changes by regulating the expression level of related genes for a long time. Because of the limited research strategy and technology, currently the specific regulatory mechanisms is still far to be clarified. In order to investigate effects of adverse environmental to the organism and make the appropriate intervention, this study use C.elegans as model organism to carried out related work.Firstly, to decipher the function of 33 globins in C. elegans under hypoxia response, we examined the expression level of all 33 globins after hypoxia treatment with different time by multiplex RT-PCR, then using feeding RNA interference to verify the result. Our result demonstrated that glb-5, glb-8 and glb-11 were upregulated after hypoxia exposure, which might have the potential role in hypoxia response. In the meantime,our results also suggested that mutiplex PCR is a useful method to indentify the mRNA expression level and can be used instead of exon array in small-scale texting.Secondly, by evaluating the growth rate, exercise behavior, brood size, life span and mortality of C. elegans, the toxicity of several heavy metals were assessed. The results showed that long-term exposure of low-concentrations heavy metal can lead to developmental disorders, abnormal exercise behavior, reproduction declined, life span reduced and other phenotypic changes. Additionally, the phenotypic changes under different heavy metals don't have positive correlation, and there is no positive correlation between the effect of chronic and acute toxicity of the same heavy metals. Based on the acute toxicity model, the gene expression level demonstrated that glb-13 in C. elegans may be related to heavy metals toxicity response. The transgenic C. elegans and mutation strain of glb-13 further confirm the results, which showed that to some extent, the phenotypic differences in mutaion strain of glb-13 can be restored by transgenic nematode. Whether hypoxic injury or heavy metal stress, both of which would undermine environmental balance of C. elegans and resulted in reactive oxygen species, and thus destroied the normal growth, development and reproduction of organisms. Based on this, we used paraquat to mimic endogenous reactive oxygen species and use C.elegans as the model organism to screen potential drugs which could against oxidative damage. The results showed that sulfated polysaccharide has significant activity which also show concentration gradient dependent pattern. Comparing with Vc, GSH and other tradtionally antioxidant, the protective effect of sulfated polysaccharide is more durable and stable. Further gene level analysis demonstrated that sulfated polysaccharide can significantly improve the expression level of nematode mitochondrial superoxide dismutase sod-2 and forkhead protein daf-16 in insulin-like receptor pathway, which initially clarify the mechanism of sulfated polysaccharide in oxidative damage against and laid the theoretical and experimental basis for the development of polysaccharide related drugs.In summary, using C. elegans as modle organism, this study investigated adverse environmental damage mechanism of hypoxia, heavy metals and reactive oxygen species, and further provided the corresponding protection strategies, which provides an important clue for the treatment of stress related diseases.