阿的平对微波损伤的干预作用

发布时间：2018-06-02 15:04

本文选题：阿的平 + 微波辐射　；参考：《中国人民解放军军事医学科学院》2011年硕士论文

【摘要】：高强度微波辐射可对机体产生生物学效应,造成多脏器系统的损伤。微波照射机体时可穿透组织,产生热效应和非热效应。热效应损伤可导致DNA合成和结构上的改变;诱导细胞凋亡;增加体内自由基含量;使氧化和抗氧化系统失衡。目前,尚未见理想的防治微波损伤药物报道。阿的平(QA),曾经是抗疟疾的常用药物。我室前期研究表明,阿的平有对抗热效应的作用,其作用可能与抑制细胞膜磷脂代谢、稳定细胞膜的作用有关,但阿的平对微波损伤的作用缺乏研究。经前期研究发现,阿的平可提高高功率微波辐射小鼠的存活率。因此,本研究首先观察了阿的平对微波损伤的BALB/c小鼠的干预作用,之后进一步观察了阿的平对微波损伤的神经前体细胞(PC12细胞分化而来)的凋亡、坏死的影响,以及组织中HSP70蛋白表达的变化。主要结果如下: 一、阿的平对微波辐射小鼠血液系统、组织病理改变的影响。 1.小鼠随机分为四组,即正常组、辐射对照组(Microwave Radiation)、阿的平低剂量组(12.6mg/kg)、阿的平高剂量组(50.4mg/kg)。接受辐射动物于照射后即刻、1d、2d、7d后完成检测,正常组动物在辐射实验后7d后完成检测。 2.辐照后小鼠外周血白细胞分类发生改变,其中白细胞和淋巴细胞计数随时间延长明显增加,给药组这些细胞数量改变的趋势均明显延缓,辐照后7d时,辐射对照组外周血白细胞计数和淋巴细胞绝对值明显高于正常组,而阿的平给药组与辐射对照组相比较明显降低,但仍然高于正常水平。 3.微波辐射后小鼠血清中细胞因子也发生改变,辐照1d后小鼠血清IL-1β水平明显升高,直至7d逐渐恢复至正常水平,而阿的平灌胃能抑制辐射引起的血清IL-1β水平升高。辐照后1d和2d时,对照组小鼠血清IL-1β与正常组相比明显升高,而给药组与正常组相比无差异;给药组小鼠血清IL-1β水平与对照组相比有所下降。血清IL-6水平从即刻至7d逐渐升高,阿的平灌胃能够明显延缓IL-6的升高,在辐射后2d内作用尤为明显。从辐照后即刻至7d给药组与对照组相比血清IL-6水平均有所降低。 4.我们观察到微波辐照后,辐射对照组小鼠的脑、心、肺、小肠和睾丸组织发生病理损伤。预先灌胃给予小鼠阿的平后,小鼠脑、心、肺、小肠和睾丸组织的病理损伤均有所减轻,细胞肿胀、间质充血等状况有所改善。二、阿的平对微波损伤的PC12分化细胞凋亡、坏死的影响,以及其对小鼠HSP70蛋白表达的影响。 1. PC12细胞用NGF进行诱导分化,七至九天后细胞突起连接成网,经NSE染色证实90%为阳性,NF染色阳性细胞约为70%。说明PC12细胞分化成功。 2.采用50mW/cm2的高功率微波,照射PC12分化细胞15min,照后3h和6h流式检测细胞凋亡、坏死率。结果发现,预先给予低剂量和高剂量阿的平组的给药组,在照后3h和6h细胞凋亡率、坏死率均低于辐射对照组,尤以阿的平高剂量组作用明显。说明阿的平可以降低细胞的凋亡和坏死比例,对细胞有一定的保护作用。 3.于不同时间点提取小鼠的脑、心、肺、睾丸组织蛋白,观察HSP70蛋白表达变化。脑、心、肺、睾丸组织蛋白表达结果显示,与辐射对照组相比阿的平组能上调HSP70蛋白的表达。调节机制尚有待进一步深入探讨。上述结果表明,阿的平能够明显延缓辐射引起的小鼠白细胞数量增加;部分抑制辐射引起的小鼠血清IL-1β和IL-6水平的增高;减小微波对小鼠脑、心、肺、小肠、睾丸组织的损伤。以上结果提示阿的平有一定的抗微波辐射效应。阿的平的这些保护机制可能与其上调HSP70蛋白表达发挥抗炎和抗凋亡作用,降低微波辐照引起的组织、细胞炎症反应和凋亡、坏死有关。
[Abstract]:High intensity microwave radiation can produce biological effects on the body, causing damage to multiple organ systems. Microwave irradiation can penetrate tissue to produce thermal and non thermal effects. Thermal damage can lead to DNA synthesis and structural changes, induce apoptosis, increase the content of free radicals in the body, and make oxidation and antioxidant systems unbalanced. There has not been an ideal report on the prevention and treatment of microwave injury drugs.
Predpine (QA), once a common anti malaria drug, has shown that the action may be related to inhibiting the metabolism of phospholipid in cell membrane and stabilizing the role of cell membrane, but the effect of predin on Microwave injury is not studied. The survival rate of mice was observed. Therefore, this study first observed the intervention effect of BALB/c on Microwave injured mice, and then further observed the apoptosis, the effect of necrosis and the changes in the expression of HSP70 protein in the tissue of PC12 cells induced by microwave injury. The main results were as follows:
(1) the effect of ATB on the blood system and histopathological changes of mice under microwave irradiation.
1. mice were randomly divided into four groups, namely, the normal group, the radiation control group (Microwave Radiation), the low dose group (12.6mg/kg) and the high dose group (50.4mg/kg). After the radiation, the animals were detected immediately after irradiation, 1D, 2D, and 7d, and the normal group was tested after the radiation experiment after the radiation test.
2. after irradiation, the white blood cell classification of the peripheral blood of mice was changed, in which the count of leukocyte and lymphocyte increased obviously with time, and the trend of the change of the number of these cells in the drug group was obviously delayed. The white blood cell count and the absolute value of lymphocyte in the radiation control group were obviously higher than that of the normal group after 7d irradiation. Compared with the radiation control group, it was significantly reduced, but still higher than the normal level.
3. the serum cytokines in mice were also changed after microwave radiation, and the serum IL-1 beta level of mice increased significantly after 1D irradiation until the 7d gradually recovered to the normal level, and the serum IL-1 beta level caused by the inhibition of radiation was increased. After irradiation, the serum IL-1 beta in the control group was significantly higher than that in the normal group when 1D and 2D were irradiated. Compared with the normal group, the serum IL-1 beta level of the mice in the administration group was lower than that of the control group. The level of serum IL-6 increased gradually from immediate to 7d, and the dosage of 7D was obviously postponing the increase of IL-6, especially in 2D after radiation. The average level of serum IL-6 water decreased from the irradiation immediately after irradiation to the 7d group and the control group. Low.
4. we observed that after microwave irradiation, the brain, heart, lung, small intestine and testicular tissue of the mice in the radiation control group had pathological damage. The pathological damage of brain, heart, lung, small intestine and testis of mice was alleviated, and the conditions of cell swelling and interstitial congestion were improved.
Two, the effect of arsenic on the apoptosis and necrosis of PC12 differentiated cells induced by microwave injury and its effect on the expression of HSP70 protein in mice.
1. PC12 cells were induced to differentiate with NGF. After seven to nine days, the cell protrusions were connected to the net, and 90% were positive by NSE staining. The NF staining positive cells were about 70%. indicating that the differentiation of PC12 cells was successful.
2. the PC12 differentiated cell 15min was irradiated with high power microwave of 50mW/cm2. The apoptosis and necrosis rate of the cells were detected by 3H and 6h flow. The results showed that the apoptosis rate and necrosis rate of 3H and 6h cells were lower than those in the radiation group, especially in the high-dose group. Ping can reduce the proportion of apoptosis and necrosis, and has a certain protective effect on cells.
3. the protein expression of HSP70 protein in the brain, heart, lung and testis of mice was observed at different time points. The expression of protein expression in brain, heart, lung and testis showed that the expression of HSP70 in the group of brain, heart, lung and testis showed that the regulation mechanism still need to be further discussed.
The above results showed that the amount of leukocytes increased in mice induced by radiation, the increase of serum IL-1 beta and IL-6 levels in mice induced by partial inhibition of radiation, and the decrease of microwave effects on the brain, heart, lung, small intestine and testicular tissue of mice. These results suggest that opiping has a certain anti microwave radiation effect. The protective mechanism may be related to the anti inflammatory and anti apoptotic effect of HSP70 protein expression, and the reduction of tissue, inflammatory response, apoptosis and necrosis caused by microwave irradiation.
【学位授予单位】：中国人民解放军军事医学科学院
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R363

【参考文献】