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        西咪替丁對(duì)0.7Gy照射小鼠嗜多染紅細(xì)胞微核的保護(hù)作用

        2015-06-28 15:42:13張俊玲何穎王慶蓉李娜蔣定文侯登勇劉玉明陳偉劉瓊李珂嫻宗杰李佳媚沈先榮
        解放軍醫(yī)學(xué)雜志 2015年12期
        關(guān)鍵詞:核率西咪替丁電離輻射

        張俊玲,何穎,王慶蓉,李娜,蔣定文,侯登勇,劉玉明,陳偉,劉瓊,李珂嫻,宗杰,李佳媚,沈先榮

        論 著

        西咪替丁對(duì)0.7Gy照射小鼠嗜多染紅細(xì)胞微核的保護(hù)作用

        張俊玲,何穎,王慶蓉,李娜,蔣定文,侯登勇,劉玉明,陳偉,劉瓊,李珂嫻,宗杰,李佳媚,沈先榮

        目的選擇輻射敏感指標(biāo)(骨髓嗜多染紅細(xì)胞微核率)評(píng)價(jià)西咪替丁對(duì)單次低劑量照射小鼠的損傷防護(hù)作用。方法健康雄性C57BL/6小鼠48只,隨機(jī)分為正常對(duì)照組、模型對(duì)照組、200mg/kg WR2721組(陽(yáng)性藥組)及7.5、15、30mg/kg西咪替丁組(n=8)。西咪替丁組于照射前2h腹腔注射給藥1次,陽(yáng)性藥組照射前連續(xù)腹腔注射給藥2d,每日1次。單次照射劑量為0.7Gy,劑量率為5.83mGy/min。照射后24h檢測(cè)小鼠外周血象,血清和肝臟中的SOD活力與MDA含量,骨髓DNA含量和骨髓嗜多染紅細(xì)胞微核率。結(jié)果與正常對(duì)照組比較,照后24h小鼠外周血白細(xì)胞顯著降低(P<0.01),嗜多染紅細(xì)胞微核率顯著升高(P<0.01),除15mg/kg西咪替丁組外,其余各組小鼠骨髓DNA含量顯著降低(P<0.01,P<0.05)。照后24h各組小鼠SOD活性和MDA含量無(wú)明顯變化。與模型對(duì)照組比較,西咪替丁各劑量組外周血白細(xì)胞和骨髓DNA含量均無(wú)明顯變化;7.5mg/kg西咪替丁組嗜多染紅細(xì)胞微核率為0.027‰,明顯低于模型對(duì)照組(P<0.01),且劑量減低系數(shù)(DRF)值達(dá)到3.338。結(jié)論西咪替丁對(duì)0.7Gy單次低劑量照射小鼠嗜多染紅細(xì)胞微核有較好的保護(hù)作用。

        西咪替??;輻射,電離;嗜多染紅細(xì)胞;微核試驗(yàn)

        與大劑量照射事件或事故的發(fā)生相比,受到低水平輻射暴露的人群更多、概率更大,除受到天然本底輻射外,人們還可能因頻繁的飛行活動(dòng)、醫(yī)學(xué)檢查、不適當(dāng)?shù)木幼…h(huán)境,以及職業(yè)照射、空間活動(dòng)等方式或途徑受到低劑量電離輻射暴露[1]。低劑量輻射暴露雖不足以引起臨床可觀察到的急性放射損傷表現(xiàn),但如不及時(shí)采取有效的監(jiān)測(cè)、危害評(píng)價(jià)以及防護(hù)措施,也會(huì)通過(guò)遠(yuǎn)后效應(yīng)的形式對(duì)健康造成危害。

        西咪替丁(cimetidine,CMTD)是第一個(gè)臨床應(yīng)用的H2受體拮抗劑,主要用于治療胃及十二直腸潰瘍、上消化道出血等疾病。近年來(lái),隨著藥理學(xué)研究的進(jìn)展,發(fā)現(xiàn)西咪替丁具有許多不同于其他H2受體拮抗劑的新用途,如預(yù)防腦出血并發(fā)應(yīng)激性潰瘍出血,預(yù)防輸血反應(yīng),治療皮膚瘙癢癥和過(guò)敏性紫癜,治療水痘、帶狀皰疹及皰疹性口炎,治療氯氮平所致流涎、小兒秋季腹瀉、流行性腮腺炎、腫瘤、痤瘡和婦女多毛癥等[2-5]。此外,Ghorbani 等[6]研究發(fā)現(xiàn),H2受體拮抗劑可有效減輕體外輻照對(duì)淋巴細(xì)胞的誘變作用。Mozdarani等[7]研究發(fā)現(xiàn),與法莫替丁相比,西咪替丁對(duì)受照小鼠具有更好的輻射保護(hù)效果,其機(jī)制可能與西咪替丁具有免疫調(diào)節(jié)作用,可減輕小鼠骨髓和淋巴組織損傷有關(guān)。Kabodanian Ardestani等[8]報(bào)道,西咪替丁和雷尼替丁可減輕亞致死劑量γ射線照射引發(fā)的生物膜損傷。Mozdarani等[9]報(bào)道,西咪替丁對(duì)低劑量快中子及高傳能線密度(linear energy transfer,LET)輻射導(dǎo)致的骨髓細(xì)胞誘裂效應(yīng)具有保護(hù)作用。本研究選用輻射敏感的評(píng)價(jià)指標(biāo),評(píng)價(jià)西咪替丁腹腔注射對(duì)0.7Gy單次低劑量電離輻射損傷的保護(hù)作用,為將其開(kāi)發(fā)為新型抗輻射藥物奠定基礎(chǔ)。

        1 材料與方法

        1.1 材料 SOD試劑盒和MDA試劑盒購(gòu)自南京建成生物有限公司;759紫外可見(jiàn)光分光光度計(jì)購(gòu)自上海奧普勒儀器有限公司,MEK-5216K型血細(xì)胞分析儀購(gòu)自日本Nihon Kohoden公司,酶標(biāo)儀購(gòu)自美國(guó)Thermo Electron公司,流式細(xì)胞儀購(gòu)自Beckman公司。C57BL/6雄性小鼠(體重20±2g,6~8周齡)購(gòu)自上海思萊克實(shí)驗(yàn)動(dòng)物有限公司(動(dòng)物質(zhì)量合格證號(hào):2008001641038)。固定液:30μl/ml SDS溶液、1%戊二醛和0.05mol/L Sorensen溶液;溶液A:Triton-100、1.0mol/L HCl和NaCl;溶液B:0.1mol/L枸櫞酸鈉溶液、0.2mol/L磷酸氫二鈉溶液、NaCl、EDTA-Na2和1mg/mL吖啶橙。

        1.2 動(dòng)物處理及取材 48只C57BL/6隨機(jī)分為6組:空白對(duì)照組、模型對(duì)照組、200mg/kg WR2721組(陽(yáng)性藥組)、7.5mg/kg西咪替丁組、15mg/kg西咪替丁組、30mg/kg西咪替丁組,每組8只。西咪替丁組于照射前2h腹腔注射給藥1次,陽(yáng)性藥組于照前連續(xù)2d腹腔注射,每天1次,200mg/(kg.d)。除空白對(duì)照組外,其余各組動(dòng)物在末次給藥2h后,于海軍醫(yī)學(xué)研究所輻照中心進(jìn)行60Co γ射線單次照射,劑量率為5.83mGy/min,照射劑量為0.7Gy。照射后24h,小鼠眼眶靜脈取血,用于外周血細(xì)胞計(jì)數(shù)和血清分離。解剖分離肝臟右葉用于SOD活性和MDA含量測(cè)定。解剖分離左右股骨,分別用于骨髓DNA含量測(cè)定和骨髓嗜多染紅細(xì)胞微核率測(cè)定。

        1.3 外周血細(xì)胞計(jì)數(shù) 取眼眶靜脈血20μl,用血細(xì)胞分析儀檢測(cè)外周血紅細(xì)胞(RBC)、血細(xì)胞比容(HCT)、紅細(xì)胞平均體積(MCV)、血小板(PLT)、白細(xì)胞(WBC)、血紅蛋白(Hb)。

        1.4 血清SOD活性和MDA含量檢測(cè) 取眼眶靜脈血,室溫放置4h后,600×g離心10min,取上清。采用試劑盒檢測(cè)血清SOD活性和MDA含量,具體操作按說(shuō)明書進(jìn)行。

        1.5 肝臟SOD活性和MDA含量檢測(cè) 取肝臟右葉,準(zhǔn)確稱量100mg,放入含900μl生理鹽水的1.5ml 的EP管內(nèi)勻漿,4℃條件下600×g離心10min,取上清。采用試劑盒檢測(cè)肝臟SOD活性和MDA含量,具體操作按說(shuō)明書進(jìn)行。

        1.6 骨髓DNA含量檢測(cè) 用注射器吸取5mmol/L CaCl2溶液10ml,用其將左股骨骨髓全部沖入離心管中;4℃冰箱靜置30min,600×g離心10min,棄上清;沉淀物中加入0.2ml/L HClO4溶液8ml,充分混合,90℃加熱15min;冷卻后600×g離心10min,取上清;將上清稀釋3倍后,在260nm處測(cè)定吸光度值。

        1.7 骨髓嗜多染紅細(xì)胞微核率檢測(cè) 用400μl小牛血清將右股骨骨髓沖入1.5ml EP管中;吸取0.2ml細(xì)胞懸液,與5ml固定液混合固定5min;300×g離心5min,棄上清;沉淀加入(0.06mol/L Sorensen緩沖液:A液:B液=4:8:32,pH7.2)混合液1ml,于冰上暗處染色30min。另制空白管,加入1ml固定液和0.2ml細(xì)胞懸液,不染色;300×g離心5min,棄上清,各測(cè)定管加入0.06mol/L Sorensen緩沖液(pH6.8)0.5ml重懸細(xì)胞,空白管加1×PBS 0.5ml重懸細(xì)胞。采用流式細(xì)胞儀檢測(cè)嗜多染紅細(xì)胞微核率。

        1.8 統(tǒng)計(jì)學(xué)處理 采用SPSS 17.0軟件進(jìn)行統(tǒng)計(jì)分析,計(jì)量資料以表示,組間比較采用方差分析,進(jìn)一步兩兩比較采用LSD-t檢驗(yàn)。P<0.05為差異有統(tǒng)計(jì)學(xué)意義。

        2 結(jié) 果

        2.1 西咪替丁對(duì)低劑量輻照后小鼠外周血象的影響 與空白對(duì)照組比較,0.7Gy輻照后小鼠WBC顯著降低(P<0.01),RBC呈下降趨勢(shì),但差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05)。與模型對(duì)照組比較,西咪替丁各劑量組WBC、PLT和RBC等指標(biāo)均無(wú)明顯變化(表1)。

        2.2 西咪替丁對(duì)低劑量輻照后小鼠抗氧化系統(tǒng)的影響 與空白對(duì)照組比較,0.7Gy輻照后24h,各組小鼠血清和肝臟SOD活力及MDA含量均無(wú)顯著變化(表2)。

        表1 西咪替丁對(duì)低劑量輻照小鼠外周血象的影響(±s,n=8)Tab. 1 Effect of cimetidine (CMTD) on blood cell counts of low-dose irradiated mice (±s,n=8)

        表1 西咪替丁對(duì)低劑量輻照小鼠外周血象的影響(±s,n=8)Tab. 1 Effect of cimetidine (CMTD) on blood cell counts of low-dose irradiated mice (±s,n=8)

        (1)P<0.05,(2)P<0.01 compared with normal control group

        Group WBC(×109/L) RBC(×1012/L) MCV(fL) PLT(×109/L) HCT(%) Hb(g/L) Normal control 4.85±1.71 10.26±0.46 44.38±0.52 940.63±133.95 45.75±2.22 134.88±8.63 Model control 1.63±0.40(2) 9.79±0.47 44.63±0.52 1030.86±117.15 45.61±6.13 126.88±6.73 200mg/kg WR2721 1.30±0.19(2) 9.35±0.51 44.13±0.35 999.63±73.39 41.68±2.79 128.88±4.16 7.5mg/kg CMTD 1.60±0.36(2) 9.79±0.33 44.63±0.52 978.00±69.73 43.70±1.65 128.38±5.55 15mg/kg CMTD 1.68±0.30(2) 9.74±0.33 44.50±0.53 1056.25±44.08(1) 43.39±1.40 127.38±6.21 30mg/kg CMTD 1.24±0.28(2) 9.39±0.40 44.00±0.76 1073.38±184.19 41.35±1.67 122.00±3.21

        表2 西咪替丁對(duì)低劑量輻照小鼠血清及肝臟SOD活力和MDA含量的影響(±s,n=8)Tab. 2 Effect of cimetidine on SOD activity and MDA content in serum and liver of low-dose irradiated mice (±s,n=8)

        表2 西咪替丁對(duì)低劑量輻照小鼠血清及肝臟SOD活力和MDA含量的影響(±s,n=8)Tab. 2 Effect of cimetidine on SOD activity and MDA content in serum and liver of low-dose irradiated mice (±s,n=8)

        Group Serum Liver SOD(U/ml) MDA(nmol/ml) SOD(U/mg.prot) MDA(nmol/mg.prot) Normal control 20.11±2.90 7.380±1.095 9.87±4.13 0.265±0.040 Model control 21.20±2.12 6.401±0.853 11.78±2.38 0.293±0.082 200mg/kg WR2721 21.66±2.28 7.769±1.020 9.42±2.64 0.210±0.077 7.5mg/kg CMTD 20.63±2.44 7.545±0.768 14.45±3.62 0.277±0.066 15mg/kg CMTD 20.80±1.07 7.957±1.105 9.55±2.46 0.227±0.054 30mg/kg CMTD 20.86±0.92 7.630±1.233 15.64±4.90 0.232±0.086

        2.3 西咪替丁對(duì)低劑量輻照后小鼠骨髓DNA含量的影響 與空白對(duì)照組比較,0.7Gy輻照后24h,除15mg/kg西咪替丁組外,其余各組小鼠骨髓DNA含量均顯著降低(P<0.05,P<0.01);與模型對(duì)照組比較,西咪替丁各劑量組小鼠骨髓DNA含量均無(wú)顯著變化(P>0.05,圖1)。

        圖1 西咪替丁對(duì)低劑量輻照小鼠骨髓DNA含量的影響(±s,n=8)Fig. 1 Effect of cimetidine on the content of bone marrow DNA of low-dose irradiated mice (±s,n=8)(1)P<0.05,(2)P<0.01 compared with normal control group

        2.4 西咪替丁對(duì)低劑量輻照后小鼠骨髓嗜多染紅細(xì)胞微核率的影響 與空白對(duì)照組比較,0.7Gy輻照后24h,模型對(duì)照組小鼠骨髓嗜多染紅細(xì)胞微核率(fMPE)和成熟紅細(xì)胞微核率(fNCE)均顯著升高(P<0.01);與模型對(duì)照組比較,200mg/kg WR2721 組fMPE、fNCE和fMPE/fNCE均顯著下降(P<0.05,P<0.01),7.5mg/kg西咪替丁組小鼠fMPE和fNCE顯著下降(P<0.01),表明7.5mg/kg西咪替丁能夠降低低劑量電離輻射導(dǎo)致的骨髓嗜多染紅細(xì)胞微核率升高,劑量減低系數(shù)(dose reduction factor,DRF)值達(dá)到3.338(表3,圖2)。

        3 討 論

        低劑量電離輻射防護(hù)藥物的研究較少,目前臨床使用的輻射防護(hù)藥主要是一些含硫的化合物,主要針對(duì)的是急性放射損傷[10],雖然有一定的保護(hù)作用,但存在一些副作用。西咪替丁是用于治療胃及十二直腸潰瘍等疾病的市售藥物,多年的臨床應(yīng)用表明其安全可靠,無(wú)明顯毒副作用。近年來(lái),有研究報(bào)道西咪替丁對(duì)電離輻射損傷有較好的保護(hù)作用,其機(jī)制可能與抗氧化和提高免疫力有關(guān)。Ching等[11]在研究H2受體拮抗劑作為羥自由基清除劑的作用時(shí)發(fā)現(xiàn),西咪替丁對(duì)羥自由基有較好的清除效果,表明其抗氧化效果較好。本研究檢測(cè)結(jié)果顯示,0.7Gy單次照射對(duì)小鼠血清和肝臟SOD活力和MDA含量無(wú)明顯影響,提示若要觀察西咪替丁對(duì)低劑量電離輻射的保護(hù)作用,需適當(dāng)加大照射劑量造成氧化系統(tǒng)損傷,再觀察西咪替丁的抗氧化作用。

        表3 西咪替丁對(duì)低劑量輻照小鼠骨髓紅細(xì)胞微核率的影響(±s,n=8)Tab. 3 Effect of cimetidine on fMPE of low-dose irradiated mice (±s,n=8)

        表3 西咪替丁對(duì)低劑量輻照小鼠骨髓紅細(xì)胞微核率的影響(±s,n=8)Tab. 3 Effect of cimetidine on fMPE of low-dose irradiated mice (±s,n=8)

        fMPE. Frequencies of micronucleated polychromatic erythrocytes; fNCE. Frequencies of normochromatic erythrocytes. DRF. Dose reduction factor. (1)P<0.05,(2)P<0.01 compared with normal control group; (3)P<0.05,(4)P<0.01 compared with model control

        Group fMPE (‰) fNCE (‰) fMPE/fNCE DRF Normal control 0.003±0.0011 0.003±0.0014 0.921±0.312 Model control 0.089±0.0170(2) 0.039±0.0111(2) 2.255±0.710(2)200mg/kg WR2721 0.015±0.0016(2)(4) 0.015±0.0033(2)(4) 1.018±0.229(3) 5.906 7.5mg/kg CMTD 0.027±0.0106(2)(4) 0.015±0.0085(2)(4) 1.758±0.168(1) 3.338 15mg/kg CMTD 0.057±0.0095(2) 0.025±0.0066(2) 2.297±0.584(2) 1.550 30mg/kg CMTD 0.060±0.0162(2) 0.022±0.0109(2) 2.765±0.518(2) 1.473

        圖2 小鼠骨髓紅細(xì)胞微核率流式細(xì)胞檢測(cè)圖Fig. 2 FACS of fMPEs in the miceA. Normal control group; B. Model control group; C. 200mg/kg WR2721 group; D. 7.5mg/kg cimetidine group; E. 15mg/kg cimetidine group; F. 30mg/kg cimetidine group

        造血系統(tǒng)是輻射的敏感靶點(diǎn)。國(guó)內(nèi)外研究表明電離輻射可引起外周血象的顯著下降。蔣定文等[12]在研究低劑量率裂變中子長(zhǎng)期照射對(duì)大鼠外周血細(xì)胞的影響時(shí)發(fā)現(xiàn),0.3Gy、0.4Gy和0.5Gy累積照射后小鼠的白細(xì)胞數(shù)顯著降低。侯登勇等[13]在研究低劑量率60Co γ射線對(duì)SD大鼠的損傷生物效應(yīng)時(shí)發(fā)現(xiàn),0.5Gy累積照射后白細(xì)胞顯著降低。本研究也發(fā)現(xiàn)0.7Gy60Co γ射線單次照射后24h,小鼠白細(xì)胞顯著降低,表明外周血白細(xì)胞對(duì)輻射高度敏感,在單次照射小于1.0Gy后24h即可產(chǎn)生顯著變化,可用作低劑量電離輻射損傷效應(yīng)和低劑量電離輻射損傷防護(hù)藥物的評(píng)價(jià)指標(biāo)之一。骨髓DNA含量反映了骨髓有核細(xì)胞的數(shù)量。陳幸華等[14]檢測(cè)了5.0Gy照射后小鼠骨髓DNA含量的變化,結(jié)果表明,照后3d小鼠骨髓DNA含量顯著降低,7d時(shí)含量有所升高,但仍明顯低于照射前。鄭秀龍等[15]研究發(fā)現(xiàn),0.7Gy60Co γ射線照射后家兔造血組織的DNA含量明顯降低,且與劑量呈依賴關(guān)系。王玨等[16]研究發(fā)現(xiàn)小鼠骨髓DNA合成率隨照射劑量的增高呈指數(shù)型下降。本研究發(fā)現(xiàn),0.7Gy60Co γ射線單次照射后24h,小鼠骨髓DNA含量顯著降低,表明骨髓DNA含量也可作為低劑量電離輻射損傷的評(píng)價(jià)指標(biāo),15mg/kg西咪替丁組小鼠骨髓DNA含量與模型對(duì)照組比較明顯上升,與空白對(duì)照組相比已無(wú)顯著差異,提示西咪替丁對(duì)照射后小鼠骨髓有核細(xì)胞的損傷有一定保護(hù)作用。

        DNA斷裂是輻射損傷的重要機(jī)制[17],未得到修復(fù)的DNA碎片可游離到細(xì)胞核外的區(qū)域并被吉姆薩染液著色,這種DNA片段被稱為微核。Mozdarani等[18]研究發(fā)現(xiàn)西咪替丁可降低中子照射后小鼠骨髓細(xì)胞的微核率。Kojima等[19]報(bào)道西咪替丁可降低5Gy X射線照射后人外周血淋巴細(xì)胞的微核率。本研究采用吖啶橙染色分析骨髓嗜多染紅細(xì)胞的微核率,結(jié)果顯示,0.7Gy劑量照射后小鼠骨髓嗜多染紅細(xì)胞微核率顯著升高,表明受照小鼠骨髓DNA受到了損傷,而7.5mg/kg西咪替丁組小鼠骨髓嗜多染紅細(xì)胞微核率顯著降低,由照射后0.089‰降至0.027‰,DRF值達(dá)到3.338,表明西咪替丁可有效減輕低劑量電離輻射對(duì)小鼠骨髓細(xì)胞的損傷。

        綜上所述,外周血白細(xì)胞、骨髓DNA含量和骨髓嗜多染紅細(xì)胞微核率可作為低劑量電離輻射損傷及其防護(hù)藥物評(píng)價(jià)的指標(biāo)。西咪替丁對(duì)0.7Gy單次低劑量照射小鼠外周血白細(xì)胞無(wú)明顯保護(hù)作用,但對(duì)受照小鼠的骨髓細(xì)胞有一定的保護(hù)作用,能夠顯著降低低劑量電離輻射后骨髓嗜多染紅細(xì)胞的微核率,促進(jìn)低劑量電離輻射所致DNA斷裂的修復(fù),但其具體分子機(jī)制待于進(jìn)一步研究。

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        [2]Zhao JS,Feng CP,Wang SC. Clinical observation of cimetidine prevention of cerebral hemorrhage complicated stress ulcer bleeding[J]. Clin Med,2000,20(5): 57-58.[趙家松,馮翠平,王書成. 西米替丁預(yù)防腦出血并發(fā)應(yīng)激性潰瘍出血的臨床觀察[J]. 臨床醫(yī)學(xué),2000,20(5): 57-58.]

        [3]Zheng SL,Zhang LM. Cimetidine investigate treatment efficacy and mechanism of mumps[J]. Chin Foreign Med Treat,2009,(33): 75.[鄭淑玲,張莉梅. 西米替丁治療流行性腮腺炎的療效觀察及機(jī)理探討[J]. 中外醫(yī)療,2009,(33): 75.]

        [4]Li ZZ. New clinical researches on cimetidine[J]. Med Forum,2014,18(10): 1330-1331.[李宗臻. 西米替丁臨床應(yīng)用新進(jìn)展[J]. 基層醫(yī)學(xué)論壇,2014,18(10): 1330-1331.]

        [5]Mou HG,Tan YX,Gao P,et al. Clinical study of acne vulgaris compound cimetidine topical treatment cream[J]. Chin J Lepr Skin Dis,2005,21(11): 879-880.[牟華光,譚艷霞,高鵬,等. 復(fù)方甲氰咪胍乳膏外用治療尋常性痤瘡的臨床研究[J]. 中國(guó)麻風(fēng)皮膚病雜志,2005,21(11): 879-880.]

        [6]Ghorbani M,Mozdarani H.In vitroradioprotective effects of histamine H2receptor antagonists against gamma-rays induced chromosomal aberrations in human lymphocytes[J]. Iran J Radiat Res,2003,1(2): 99-104.

        [7]Mozdarani H,Salimi M,Froughizadeh M. Effect of cimetidine and famotidine on survival of lethally gamma irradiated mice[J]. Iran J Radiat Res,2008,5(4): 187-194.

        [8]Kabodanian Ardestani S,Mahmood Janlow M,Kariminia A,et al. Effect of cimetidime and ranitidine on lipid profile and lipid peroxidation in γ-irradiated mice[J]. Acta Medica Iranica,2004,42(3): 198-204.

        [9]Mozdarani H,Gharbali A. Radioprotective effects of cimetidine in mouse bone marrow cells exposed to gamma-rays as assayed by the micronucleus test[J]. Int J Radiat Biol,1993,64(2): 189-194.

        [10] Jia C,Zhang LZ,Xing S,et al. Protective effect of α-tocopherol succinate against early hematopoietic injury in mice with acute radiation sickness[J]. Med J Chin PLA,2014,39(4): 333-337.[賈超,張劉珍,邢爽,等. α-生育酚琥珀酸酯對(duì)急性放射病小鼠早期造血損傷的防護(hù)作用觀察[J]. 解放軍醫(yī)學(xué)雜志,2014,39(4): 333-337.]

        [11] Ching TL,Haenen GR,Bast A. Cimetidine and other H2receptor antagonists as powerful hydroxyl radical scavengers[J]. Chem Biol Interact,1993,86(2): 119-127.

        [12] Jiang DW,Lei CX,Shen XR,et al. Effects of long-term,low dose rate fission neutron irradiation on the peripheral hematological cells in rat[J]. Chin J Radiol Health,2008,17(1): 12.[蔣定文,雷呈祥,沈先榮,等. 低劑量率裂變中子長(zhǎng)期照射對(duì)大鼠外周血細(xì)胞的影響[J]. 中國(guó)輻射衛(wèi)生,2008,17(1): 12.]

        [13] Hou DY,Shen XR,He Y,et al. Effect of low-dose rate60Co γ-ray ionizing radiation on SD Rats[J]. Chin J Radiol Health,2012,21(1): 11-12.[侯登勇,沈先榮,何穎,等. 低劑量率60Co γ射線對(duì)SD大鼠的損傷生物效應(yīng)研究[J]. 中國(guó)輻射衛(wèi)生,2012,21(1): 11-12.]

        [14] Chen XH,Luo CJ,Guo ZH,et al. Changes of cell cycle and DNA content in bone marrow stromal cells after radiation injury in mice[J]. Acta Acad Med Mil Tertiae,1996,18(3): 209-210.[陳幸華,羅成基,郭朝華,等. 5.0Gy放射損傷對(duì)小鼠早期骨髓造血基質(zhì)細(xì)胞周期及其DNA含量的影響[J]. 第三軍醫(yī)大學(xué)學(xué)報(bào),1996,18(3): 209-210.]

        [15] Zheng XL,Wu DL,Liu QN,et al. Changes in the DNA of hematopoietic tissue of animals after ionizing radiation[J]. Acad J Second Mil Med Univ,1981,(4): 317-320.[鄭秀龍,吳德林,劉巧年,等. 電離輻射后動(dòng)物造血組織內(nèi)DNA的變化[J]. 第二軍醫(yī)大學(xué)學(xué)報(bào),1981,(4): 317-320.]

        [16] Wang J,Zhang SY,Wang BQ,et al. The effect of neutron-γ ray irradiation effect on mouse bone marrow mixed DNA synthesis[J]. Bullet Acad Mil Med Sci,1982,(2): 133-137.[王玨,張水英,王寶勤,等. 中子-γ射線混合照射對(duì)小鼠骨髓DNA合成的影響[J]. 軍事醫(yī)學(xué)科學(xué)院院刊,1982,(2): 133-137.]

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        [18] Mozdarani H,Khoshbin-Khoshnazar AR.In vivoprotection by cimetidine against fast neutron-induced micronuclei in mouse bone marrow cells[J]. Cancer Lett,1998,124(1): 65-71.

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        Protective effects of cimetidine on micronucleated polychromatic erythrocytes in mice irradiated with 0.7Gy

        ZHANG Jun-ling,HE Ying,WANG Qing-rong,LI Na,JIANG Ding-wen,HOU Deng-yong,LIU Yu-ming,CHEN Wei,LIU Qiong,LI Ke-xian,ZONG Jie,LI Jia-mei,SHEN Xian-rong*
        Department of Protection Medicine,Naval Medical Research Institute,Shanghai 200433,China
        *< class="emphasis_italic">Corresponding author,E-mail: xianrong_sh@163.com

        ,E-mail: xianrong_sh@163.com
        This work was supported by the Major Projects of National Science and Technology (2004ZX09J14103-07B)

        ObjectiveTo study the radioprotective effect of cimetidine on single low-dose irradiated mice with radiosensitive detection indexes.MethodsForty-eight healthy male C57BL/6 mice were randomly divided into normal control group,model control group,positive group (200mg/kg WR2721) and cimetidine groups (7.5mg/kg,15mg/kg and 30mg/kg). The mice were given intraperitoneal injection of cimetidine 2h before irradiation in cimetidine groups and WR2721 before irradiation once a day for two days in positive group. All the mice except those in normal control group were irradiated with 0.7Gy60Co γ-ray at 5.83mGy/min rate. Peripheral blood cells,superoxide dismutase (SOD) activity and malondialdehyde (MDA) content both in serum and liver,bone marrow DNA content and frequency of micronucleated polychromatic erythrocytes (fMPEs) were determined 24h after irradiation.ResultsCompared with normal control group,the peripheral white blood cells (WBCs) of irradiated mice decreased significantly (P<0.01),and fMPEs increased significantly (P<0.01) after irradiation. Except for 15mg/kg cimetidine group,the bone marrow DNA content was decreased significantly after irradiation (P<0.01,P<0.05). The SOD activity and MDA content in irradiated mice showed no significant difference compared with that of normal mice. Compared with model control group,peripheral WBCs and bone marrow DNA content showed no significant changes in treatment groups. The fMPE of 7.5mg/kg cimetidine group was 0.027‰,which was decreased significantly compared with that of model control group (P<0.01),and the dose reduction factor (DRF) of 7.5mg/kg cimetidine group was 3.338.ConclusionCimetidine has good protective effect on micronucleated polychromatic erythrocytes (MPEs) in mice irradiated by 0.7Gy in single low-dose.

        cimitidine; radiation,ionizing; polychromatic erythrocytes; micronucleus tests

        R148

        A

        0577-7402(2015)12-0950-05

        10.11855/j.issn.0577-7402.2015.12.03

        2015-07-09;

        2015-08-13)

        (責(zé)任編輯:李恩江)

        國(guó)家科技重大專項(xiàng)課題(2004ZX09J14103-07B)

        張俊玲,工學(xué)碩士。主要從事輻射防護(hù)醫(yī)學(xué)方面的研究

        200433 上海 海軍醫(yī)學(xué)研究所輻射防護(hù)效應(yīng)研究室(張俊玲、何穎、王慶蓉、李娜、蔣定文、侯登勇、劉玉明、陳偉、劉瓊、李珂嫻、宗杰、李佳媚、沈先榮)

        沈先榮,E-mail:xianrong_sh@163.com

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