Font Size: a A A

Exploring Early Marker Of Pulmanary Fibrosis And The Protetion Of Se-MT By SELDI-TOF-MS

Posted on:2005-10-23Degree:MasterType:Thesis
Country:ChinaCandidate:Y GaoFull Text:PDF
GTID:2144360122498647Subject:Pharmacology
Abstract/Summary:PDF Full Text Request
Metallothionein (MT) is a group of cysteine-rich, low molecular weight, metal-binding intracellular protein which are widely distributed in nature. It has been proved that MT is closely correlative with essential metal metabolism, heavy metal detoxification, anti-radiation, anti-oxidation, cleaning free radical, apoptosis and proliferation of tumor cells and energy metabolism et al.SELDI is a new technology which developed after genechip in the end of 20th century.In the era of post-genomics,scientists have taken cognizance that the panoramic analysis of proteimics is the basic for people to understand a gravedisease, and estimating the function of an unknowen gene must be confirmed on the level of protein. SELDI can combine proteinchip technology with Mass Spectrometry and has some merits including not only high quantum,high efficiency,good repeation of chip but also high sensitivity of Mass. The development of knowledge and technology in proteomics has provided a new way to study many kind of diseases.The aim of this study is to prove:(1)establishing two kinds of animal model of pulmonary fibrosis; (2) establishing lung tissue and serum proteinchip Spectrometry including standard and injure models by SELDI technology, exploring the early biomarker, eatablishing strong especially biological observing marker closely relatated to the pulmonary fibrosis . (3) evaluating and indentifing the biological effect of Se-MT in order to diagnose forepart pulmonary fibrosis and evaluate the effect of some medicines on clinic.In the first part, we select the kind of IMAC-Cu proteinchip to indentify the Se-MT on the basic that MT has a metal chelated character especially strong power to combine with copper. The results showed that: Compared with the proteinchip Spectrometry of MT standard sample from Sigma Co., the expression of MT in mice lung tissuesinduced by organic selenium is higher than that in control groups. The results prove that organic selenium has strong ability to induce MT and lung can be induced to produce MT. These results provide a good reference for the further study.In the second part, we establish the radiate lung injure model of mice , and evaluate the protective effects of MT induced by organic selenium (Se-malt). The results showed that: the living time of mice induced by Se-malt is obviosely longer than the radiate injure groups (P<0.05) .Meanwhile,we indentify 2 and 1 biomarker respectively in 14 and 7 days after radiation of mice serum and lung tissue that can distinguish the control and injure groups by SELDI ,moreover the expression of these protein in Se treated group is similar with control group.In this way ,we ensure the protein biomarker of lung radiate injure model.This way maybe used as a new method in the future study.In the third part, we establish mice pulmonary fibrosis model by chemistry substance PQ and study the protection of Se-MT. The pathology results show that the lung tissue structure of mice in Se treated group is similar with control group ,while the mice in the injure group show pulmonary fibrosis pathology changes. The proteinchip spectrometry by SELDI-TOF-MASS show that there are 4 protein marker that can distinguish the control and injure group and the change depends on the dose. There are no significant changes of protein expression between in Se treated group and in control group, in this study the protein fingerprinting pattern of serum and liver tissue lyses established The discovery of these marker protein not only provided a novel powerful proteomic model ,but also hopely captured the early marker in forepart pulmonary fibrosis . This non-injury method could be widely used in both clinic trial and pre-clinic study in the future.
Keywords/Search Tags:Metallothionein, Selenium, pulmonary fibrosis, Protein fingerprinting
PDF Full Text Request
Related items