低剂量辐射对阿霉素所致心肌损伤保护作用及机制的初步探讨

发布时间：2018-05-08 16:08

本文选题：低剂量辐射 + 阿霉素　；参考：《吉林大学》2012年硕士论文

【摘要】：低剂量辐射与大剂量辐射对生物体产生的生物学效应是截然不同的，目前研究主要集中在低剂量辐射诱导生物体产生的兴奋性效应和适应性反应。兴奋性效应主要表现为增强机体免疫功能、促进机体正常细胞增殖等。适应性反应是指机体对后续的大剂量辐射引起的损伤产生耐受，从而减轻大剂量辐射引起的损伤。目前研究已证实低剂量辐射不能诱导肿瘤细胞产生兴奋性效应、适应性反应，而且对部分肿瘤细胞还具有协同放、化疗杀伤作用。但是否能将LDR应用于抗肿瘤药物心肌损伤的保护，目前国内外尚未见报道。本研究旨在论证低剂量辐射对化疗药物阿霉素引起的心肌损伤是否产生保护作用，并探讨其作用机制。本实验设6个试验组，包括对照组及荷瘤鼠组。荷瘤鼠组随机分为5组，具体分组为：假照组；低剂量辐射组；阿霉素组；低剂量辐射联合阿霉素组，此组分2个亚组：低剂量辐射后间隔6小时给予阿霉素组；低剂量辐射后间隔12小时给予阿霉素组。通过观察记录各组裸鼠的饮食、活动和体重变化，并测量记录移植瘤生长情况，称瘤重，计算抑瘤率，探讨低剂量辐射联合阿霉素对乳腺癌裸鼠的抑瘤作用。结果发现单独阿霉素组裸鼠一般状态极差，消瘦明显，，活动迟缓，饮食、饮水明显减少，与低剂量辐射联合阿霉素组比，体重减低明显。此外，单独低剂量辐射组较假照组比抑瘤率没有明显增加，联合阿霉素组抑瘤率较单独阿霉素组稍增高。此结果说明低剂量辐射可以改善阿霉素化疗后乳腺癌荷瘤鼠的一般状态，并且不能诱导乳腺癌荷瘤鼠肿瘤组织产生兴奋性效应及适应性适应，而且可以一定程度上协同阿霉素抑制肿瘤生长。通过观察荷瘤鼠新鲜心肌组织抗氧化酶SOD、GSH-Px活力及脂质过化产物MDA含量变化，论证低剂量辐射对阿霉素诱导的心肌损伤是否保护作用。结果显示阿霉素组心肌抗氧化酶SOD、GSH-Px活力明显降，而脂质过氧化产物MDA含量明显增高，与低剂量辐射联合阿霉素组，差异明显，结果表明低剂量辐射可以通过增强心肌抗氧化酶活性，减脂质过氧化产物生成，从而减轻阿霉素诱导的心肌损伤。通过免疫组化方法检测心肌组织VEGF、HIF-1α、SOD蛋白及肿瘤组VEGF、HIF-1α蛋白表达，探讨低剂量辐射对心肌及肿瘤组织血管形成影响，此外，进一步论证低剂量辐射对心肌抗氧化酶的作用，结果显示剂量辐射可以一定程度上抑制肿瘤组织VEGF、HIF-1α蛋白表达，同时进心肌组织HIF-1α、SOD蛋白的表达。综上，低剂量辐射可以用于阿霉所致心肌损伤的保护，一方面可以协同抑瘤，一方面可以增强心肌抗氧酶活性，降低及防治阿霉素所致心肌损伤，以上实验结果分析为低剂量射应用于阿霉素诱导心肌损伤的保护提供了充实的证据。
[Abstract]:The biological effects of low dose radiation and large dose radiation are very different. The current research mainly focuses on the excitatory and adaptive responses produced by low dose radiation induced organisms. The excitatory effects are mainly manifested in enhancing the immune function of the body and promoting the normal cell proliferation. The body is tolerant to subsequent damage caused by large dose radiation, thus reducing the damage caused by large doses of radiation. Current studies have shown that low dose radiation can not induce excitability, adaptive response and synergistic radiation to some tumor cells, but whether LDR can be applied to the anti tumor cells. The protection of myocardial injury of tumor drugs has not been reported at home and abroad. The purpose of this study is to demonstrate the protective effect of low dose radiation on the myocardial injury induced by doxorubicin, and to explore the mechanism of its action.
The experiment set up 6 experimental groups, including the control group and the tumor bearing rat group. The mice group was randomly divided into 5 groups, which were divided into three groups: the fake group, the low dose radiation group, the adriamycin group, the low dose radiation combined with adriamycin group, 2 subgroups: the low dose radiation interval was given to the amycomycin group for 6 hours, and the low dose radiation interval was given 12 hours. Adriamycin group.
By observing the diet, activity and weight change of the nude mice and measuring the growth of the transplanted tumor, the weight of the tumor was recorded, the tumor suppressor rate was calculated, and the anti tumor effect of doxorubicin combined with adriamycin on the nude mice was investigated. The results showed that low dose radiation could improve the general state of breast cancer rats after doxorubicin chemotherapy, and that the low dose radiation could improve the general state of the breast cancer rats after adriamycin chemotherapy, and the results showed that the low dose radiation could improve the general state of the breast cancer mice after adriamycin chemotherapy, and the results showed that the low dose radiation could improve the general state of the breast cancer rats. It can induce excitatory effect and adaptive adaptation in tumor tissue of breast cancer bearing mice, and can synergy adriamycin to inhibit tumor growth to some extent.
The effects of low dose radiation on adriamycin induced myocardial injury were observed by observing the changes of antioxidant enzyme SOD, GSH-Px activity and the content of MDA in the fresh myocardium of the tumor bearing mice. The results showed that the myocardial antioxidant enzyme SOD, GSH-Px activity of the adriamycin group decreased significantly, and the MDA content of the lipid peroxidation product was significantly higher and lower than that of the lipid peroxidation products. The difference between dose radiation and adriamycin group was obvious. The results showed that low dose radiation could reduce the myocardial injury induced by adriamycin by enhancing the activity of myocardial antioxidant enzymes and the production of lipid peroxidation products.
The expression of VEGF, HIF-1 a, SOD protein and VEGF, HIF-1 alpha protein in the tumor group was detected by immunohistochemical method. The effect of low dose radiation on the angiogenesis of myocardium and tumor tissue was investigated. Furthermore, the effect of low dose radiation on myocardial antioxidant enzyme was further demonstrated. The results showed that dose radiation could inhibit the VEG of tumor tissue to a certain extent. F, HIF-1 alpha protein expression, and the expression of HIF-1 alpha, SOD protein in myocardial tissue. Combined, low dose radiation can be used for the protection of myocardial injury caused by almilion. On one hand, it can synergistically inhibit the tumor. On the one hand, it can enhance the activity of myocardial antioxygenase, reduce and prevent the injury of myocardium caused by adriamycin. The above experimental results are analyzed for low dose injection application. It provides substantial evidence for the protection of adriamycin induced myocardial injury.

【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R142

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