Effect Of The Multiplication In Colon Cancer By Oxidative Stress After Exposure To Chronic Intermittent Hypoxia

In the recent years, many researcher paid more attention to obstructive sleep apnea-hypopnea syndrome (OSAHS), which proved to be correlative with oxidative stress (OS) induced by chronic intermittent hypoxia (IH), and this had brought about on the damage of organs by OS. Some studies had showed that tumors were closely related to hypoxia, but whether or not tumors were correlative with oxidative stress is unknown. In this study, we set up the IH cell model and IH nude mice model, and try to determine the level of oxidative stress in the hosts with colonic neoplasm when expose to IH, also, we will detect the relationship between oxidative stress and colon neoplasm.This thesis consists of three parts:the relationship between advanced oxidation protein products (AOPP) and oxidative stress in patients with OSAHS, the relationship between advanced oxidation protein and VEGF, TGF-β1 in colon cancer cells after exposure to intermittent hypoxia and the effect of the multiplication in colon cancer by oxidative stress after exposure to chronic intermittent hypoxia.Chapter 1 The relationship between advanced oxidation protein products (AOPP) and oxidative stress in patients with OSAHSOBJECTIVES:To investigate the relationship between advanced oxidation protein products (AOPP) and oxidative stress in the patients with obstructive sleep apnea-hypopnea syndrime(OSAHS).METHODS:47 patients with OSAHS and 48normal controls were studied. AOPP, superoxido (SOD), malonaldehyde (MDA), glutathione peroxidase (GSH-PX) in morning blood samples were measured by standard techniques. The datas were dealed with SPSS 13.0, and numeric variables were represented by mean ± standard deviation O, one- way ANOVA test was applied when comparing paired samples. As usual, it was thought to have statistical significance when P<0.05.RESULTS:(1) Plasma AOPP and MDA were significantly higher in OSAHS when compared with those in contrlo group (both P<0.01). Plasma SOD and GSH-PX were significantly higher in OSAHS compared with those in control group (both P<0.01). There were significant differences in the plasma AOPP, MDA, SOD and GSH-PX among three stages of OSAHS (all P<0.01). Plasma AOPP and MDA were increased with the progression of OSAHS, and SOD and GDH-PX were gradually decreased when OSAHS become worse. (2) Plasma AOPP correlated well with MDA, SOD and GSH-PX, moreover, AOPP was positively correlated with apnea hyponea index or lowest oxygen saturation.CONCLUSIONS:AOPP is closely related to oxidative streess in OSAHS. The development of OSAHS is closely related to the oxidative stress and the anti-oxidative ability. The level of oxidative stress was increased and the anti-oxidative ability was decreased when OSAHS was aggravating. AOPP is a alternative index reflecting both oxidative streess and tissue injury in patients with OSAHS.Chapter 2 The relationship between advanced oxidation protein products (AOPP) and VEGF, TGF-β1 in colon cancer cells after exposure to intermittent hypoxia.OBJECTIVES:To determine the effects of intermittent hypoxia (IH) on the colonic neoplasm cell (SW480 cell lines) and the expression of advanced oxidation protein products (AOPP), and its relationship with VEGF, TGF-β1.METHODS:Set up the IH cell model, cells were divided into three groups: group A:IH group, group B:continuous hyposia (CH) group, group C:normoxia group. The concentration of AOPP, VEGF was measured with ELISA method, while malonaldehyde (MDA), glutathione peroxidase (GSH-PX) with Xantione oxidase test, and TGF-β1 Western blot assay. The datas were dealed with SPSS 13.0, and numeric variables were represented by mean ± standard deviation (), one-way ANOVA test was applied when comparing paired samples. As usual, it was thought to have statistical significance when P<0.05.RESULTS:(1) AOPP and MDA were significantly higher in group A and group B when compared with those in control group (both P<0.01). SOD and GSH-PX were significantly lower in group A and group B when compared with those in control group (both P<0.01). (2)The concentration of AOPP was positively correlated with MDA, VEGF and TGF-β1, but negativelycorrelated with SOD, and has no correlated with GSH-PX.CONCLUSIONS:The damage of protein oxidation was higher in group when compared with group B and group C, which is related to oxidative stress, The express level of VEGF and TGF-β1 was high in IH group than CH group, was closely related to AOPP.Chapter 3 Effect of the multiplication in colon cancer by oxidative stress after exposure to chronic intermittent hypoxia.OBJECTIVES:To determine the effects of intermittent hypoxia (IH) on the colonic neoplasm cell (SW480 cell lines) and the expression of advanced oxidation protein products (AOPP), and its relationship with MVD (microvessel density), VEGF and TGF-β1.METHODS:Set up the CIH mude mice model, mices were divided into four groups:group A:room air, no tumor, group B:room air, colonization tumor, group C: intermittent hypoxia, no tumor and D group:intermittent hypoxia, colonization tumor. The concentration of AOPP,8-OHdG, VEGF were measured with ELISA, while nitric oxide (NO) and superoxide dismutase (SOD) with Xantione oxidase test, iNOSmRNA detect by PCR and TGF-β1 by Western blot assay. The datas were dealed with SPSS 13.0, and numeric variables were represented by mean ± standard deviation (x+s), one-way ANOVA test was applied when comparing paired samples. As usual, it was thought to have statistical significance when P<0.05.RESULTS:(1) The colonization tumors were bigger but lighter in group B when compare to group. (2)AOPP,8-OHdG and NO were significantly higher in group D when compared with those in group A, B and C (both P<0.01). SOD were significantly lower in group D when compared with those in group A, B and C (both P<0.01). (3)The lever of VEGF, TGF-β1, MVD in group D is higher than group B.AOPP was positively correlated with MVD, VEGF and TGF-β1, but negativelycorrelated with SOD.CONCLUSIONS:The damage of protein oxidation and oxidative stress is serious when exposure to chronic internittent hypoxia (CIH). The lever of VEGF, TGF-β1, MVD in colonization tumors is higher in chronic internittent hypoxia than room air condition. The oxidative stress induce by CIH had promoted the tumor. GENERAL CONCLUSION:1. It was indicated that the AOPP is closely related to oxidative streess in OSAHS.2. The level of oxidative stress was increased and the anti-oxidative ability was decreased when OSAHS was aggravating.3. The damage of protein oxidation was higher in group when compared with group B and group C, which is related to oxidative stress.4. The level of VEGF and TGF-β1 was high in CIH group than room air group, which was closely related to AOPP.