發(fā)布時間：2018-06-02 15:04

  本文選題：阿的平 + 微波輻射�。� 參考：《中國人民解放軍軍事醫(yī)學(xué)科學(xué)院》2011年碩士論文

【摘要】：高強(qiáng)度微波輻射可對機(jī)體產(chǎn)生生物學(xué)效應(yīng),造成多臟器系統(tǒng)的損傷。微波照射機(jī)體時可穿透組織,產(chǎn)生熱效應(yīng)和非熱效應(yīng)。熱效應(yīng)損傷可導(dǎo)致DNA合成和結(jié)構(gòu)上的改變;誘導(dǎo)細(xì)胞凋亡;增加體內(nèi)自由基含量;使氧化和抗氧化系統(tǒng)失衡。目前,尚未見理想的防治微波損傷藥物報道。 阿的平(QA),曾經(jīng)是抗瘧疾的常用藥物。我室前期研究表明,阿的平有對抗熱效應(yīng)的作用,其作用可能與抑制細(xì)胞膜磷脂代謝、穩(wěn)定細(xì)胞膜的作用有關(guān),但阿的平對微波損傷的作用缺乏研究。經(jīng)前期研究發(fā)現(xiàn),阿的平可提高高功率微波輻射小鼠的存活率。因此,本研究首先觀察了阿的平對微波損傷的BALB/c小鼠的干預(yù)作用,之后進(jìn)一步觀察了阿的平對微波損傷的神經(jīng)前體細(xì)胞(PC12細(xì)胞分化而來)的凋亡、壞死的影響,以及組織中HSP70蛋白表達(dá)的變化。主要結(jié)果如下: 一、阿的平對微波輻射小鼠血液系統(tǒng)、組織病理改變的影響。 1.小鼠隨機(jī)分為四組,即正常組、輻射對照組(Microwave Radiation)、阿的平低劑量組(12.6mg/kg)、阿的平高劑量組(50.4mg/kg)。接受輻射動物于照射后即刻、1d、2d、7d后完成檢測,正常組動物在輻射實驗后7d后完成檢測。 2.輻照后小鼠外周血白細(xì)胞分類發(fā)生改變,其中白細(xì)胞和淋巴細(xì)胞計數(shù)隨時間延長明顯增加,給藥組這些細(xì)胞數(shù)量改變的趨勢均明顯延緩,輻照后7d時,輻射對照組外周血白細(xì)胞計數(shù)和淋巴細(xì)胞絕對值明顯高于正常組,而阿的平給藥組與輻射對照組相比較明顯降低,但仍然高于正常水平。 3.微波輻射后小鼠血清中細(xì)胞因子也發(fā)生改變,輻照1d后小鼠血清IL-1β水平明顯升高,直至7d逐漸恢復(fù)至正常水平,而阿的平灌胃能抑制輻射引起的血清IL-1β水平升高。輻照后1d和2d時,對照組小鼠血清IL-1β與正常組相比明顯升高,而給藥組與正常組相比無差異;給藥組小鼠血清IL-1β水平與對照組相比有所下降。血清IL-6水平從即刻至7d逐漸升高,阿的平灌胃能夠明顯延緩IL-6的升高,在輻射后2d內(nèi)作用尤為明顯。從輻照后即刻至7d給藥組與對照組相比血清IL-6水平均有所降低。 4.我們觀察到微波輻照后,輻射對照組小鼠的腦、心、肺、小腸和睪丸組織發(fā)生病理損傷。預(yù)先灌胃給予小鼠阿的平后,小鼠腦、心、肺、小腸和睪丸組織的病理損傷均有所減輕,細(xì)胞腫脹、間質(zhì)充血等狀況有所改善。 二、阿的平對微波損傷的PC12分化細(xì)胞凋亡、壞死的影響,以及其對小鼠HSP70蛋白表達(dá)的影響。 1. PC12細(xì)胞用NGF進(jìn)行誘導(dǎo)分化,七至九天后細(xì)胞突起連接成網(wǎng),經(jīng)NSE染色證實90%為陽性,NF染色陽性細(xì)胞約為70%。說明PC12細(xì)胞分化成功。 2.采用50mW/cm2的高功率微波,照射PC12分化細(xì)胞15min,照后3h和6h流式檢測細(xì)胞凋亡、壞死率。結(jié)果發(fā)現(xiàn),預(yù)先給予低劑量和高劑量阿的平組的給藥組,在照后3h和6h細(xì)胞凋亡率、壞死率均低于輻射對照組,尤以阿的平高劑量組作用明顯。說明阿的平可以降低細(xì)胞的凋亡和壞死比例,對細(xì)胞有一定的保護(hù)作用。 3.于不同時間點提取小鼠的腦、心、肺、睪丸組織蛋白,觀察HSP70蛋白表達(dá)變化。腦、心、肺、睪丸組織蛋白表達(dá)結(jié)果顯示,與輻射對照組相比阿的平組能上調(diào)HSP70蛋白的表達(dá)。調(diào)節(jié)機(jī)制尚有待進(jìn)一步深入探討。 上述結(jié)果表明,阿的平能夠明顯延緩輻射引起的小鼠白細(xì)胞數(shù)量增加;部分抑制輻射引起的小鼠血清IL-1β和IL-6水平的增高;減小微波對小鼠腦、心、肺、小腸、睪丸組織的損傷。以上結(jié)果提示阿的平有一定的抗微波輻射效應(yīng)。阿的平的這些保護(hù)機(jī)制可能與其上調(diào)HSP70蛋白表達(dá)發(fā)揮抗炎和抗凋亡作用,降低微波輻照引起的組織、細(xì)胞炎癥反應(yīng)和凋亡、壞死有關(guān)。
[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.
【學(xué)位授予單位】：中國人民解放軍軍事醫(yī)學(xué)科學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2011
【分類號】：R363

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