药学研究
藥學研究
약학연구
JOURNAL OF PHARMACEUTICAL RESEARCH
2014年
7期
384-385,405
,共3页
右旋雷贝拉唑钠%小鼠%染色体损伤
右鏇雷貝拉唑鈉%小鼠%染色體損傷
우선뢰패랍서납%소서%염색체손상
The right - handed rabeprazole%Mouse%Chromosomal damage
目的：通过对右旋雷贝拉唑钠小鼠灌胃给药微核试验的研究，预测其遗传毒性，降低临床用药风险。方法健康雄性 BALB/ c 小鼠60只，按体重随机分为低、中、高剂量组、溶媒对照组和阳性对照组，每组6只。分别灌胃给予右旋雷贝拉唑钠125、250、500 mg·kg -1，溶媒对照组灌胃给予灭菌蒸馏水，给药体积40 mL·kg -1；阳性对照组腹腔注射给予环磷酰胺50 mg·kg -1，给药体积为20 mL·kg -1。于给药后24 h 和48 h 将动物颈椎脱臼处死，取胸骨骨髓常规制片、姬姆萨染色。显微镜双盲法阅片，每只小鼠观察2000个嗜多染红细胞（PCE），计数出现微核的嗜多染红细胞，计算微核率，并计算嗜多染红细胞与总红细胞比例。结果研究结果显示，小鼠灌胃给药24 h后，低、中、高剂量组的骨髓微核发生率分别为1.92‰、1.58‰、1.83‰，与溶媒对照组（1.75‰）相比无显著性差异，但其与阳性对照组之间（23.92‰）有非常显著性差异（P ﹤0.01）。在灌胃给药48 h 后，低、中、高剂量组的骨髓微核发生率分别为1.75‰、1.58‰、1.50‰，与溶媒对照组（1.83‰）相比无显著性差异，但其与阳性对照组（21.83‰）之间具有非常显著性差异（P ﹤0.01）。结论在本试验条件下，右旋雷贝拉唑钠小鼠灌胃给药微核试验结果为阴性。
目的：通過對右鏇雷貝拉唑鈉小鼠灌胃給藥微覈試驗的研究，預測其遺傳毒性，降低臨床用藥風險。方法健康雄性 BALB/ c 小鼠60隻，按體重隨機分為低、中、高劑量組、溶媒對照組和暘性對照組，每組6隻。分彆灌胃給予右鏇雷貝拉唑鈉125、250、500 mg·kg -1，溶媒對照組灌胃給予滅菌蒸餾水，給藥體積40 mL·kg -1；暘性對照組腹腔註射給予環燐酰胺50 mg·kg -1，給藥體積為20 mL·kg -1。于給藥後24 h 和48 h 將動物頸椎脫臼處死，取胸骨骨髓常規製片、姬姆薩染色。顯微鏡雙盲法閱片，每隻小鼠觀察2000箇嗜多染紅細胞（PCE），計數齣現微覈的嗜多染紅細胞，計算微覈率，併計算嗜多染紅細胞與總紅細胞比例。結果研究結果顯示，小鼠灌胃給藥24 h後，低、中、高劑量組的骨髓微覈髮生率分彆為1.92‰、1.58‰、1.83‰，與溶媒對照組（1.75‰）相比無顯著性差異，但其與暘性對照組之間（23.92‰）有非常顯著性差異（P ﹤0.01）。在灌胃給藥48 h 後，低、中、高劑量組的骨髓微覈髮生率分彆為1.75‰、1.58‰、1.50‰，與溶媒對照組（1.83‰）相比無顯著性差異，但其與暘性對照組（21.83‰）之間具有非常顯著性差異（P ﹤0.01）。結論在本試驗條件下，右鏇雷貝拉唑鈉小鼠灌胃給藥微覈試驗結果為陰性。
목적：통과대우선뢰패랍서납소서관위급약미핵시험적연구，예측기유전독성，강저림상용약풍험。방법건강웅성 BALB/ c 소서60지，안체중수궤분위저、중、고제량조、용매대조조화양성대조조，매조6지。분별관위급여우선뢰패랍서납125、250、500 mg·kg -1，용매대조조관위급여멸균증류수，급약체적40 mL·kg -1；양성대조조복강주사급여배린선알50 mg·kg -1，급약체적위20 mL·kg -1。우급약후24 h 화48 h 장동물경추탈구처사，취흉골골수상규제편、희모살염색。현미경쌍맹법열편，매지소서관찰2000개기다염홍세포（PCE），계수출현미핵적기다염홍세포，계산미핵솔，병계산기다염홍세포여총홍세포비례。결과연구결과현시，소서관위급약24 h후，저、중、고제량조적골수미핵발생솔분별위1.92‰、1.58‰、1.83‰，여용매대조조（1.75‰）상비무현저성차이，단기여양성대조조지간（23.92‰）유비상현저성차이（P ﹤0.01）。재관위급약48 h 후，저、중、고제량조적골수미핵발생솔분별위1.75‰、1.58‰、1.50‰，여용매대조조（1.83‰）상비무현저성차이，단기여양성대조조（21.83‰）지간구유비상현저성차이（P ﹤0.01）。결론재본시험조건하，우선뢰패랍서납소서관위급약미핵시험결과위음성。
Objective To study mouse micronucleus test of rabeprazole sodium administered orally,evaluation dextral rabeprazole sodium on chromosome damage in animals to predict their genetic toxicity. Methods Healthy male BALB / c mice were 60,were randomly divided into low,medium and high dose groups,vehicle control group and positive control group,n = 6. Intragastric administration of rabeprazole sodium were handed 125,250,500 mg·kg - 1 ,and vehicle control group was given sterile distilled water,dosing volume 40 mL·kg - 1;Positive control group was given intraperitoneal injec-tion of cyclophosphamide amide 50 mg·kg - 1 ,dose volume of 20 mL·kg - 1 . After 24 h and 48 h of administration the ani-mals were killed by cervical dislocation,took sternum bone marrow conventional producers,Giemsa staining. Microscopy double - blind read the piece,each mouse was observed 2 000 polychromatic erythrocytes(PCE),micronuclei count ap-peared polychromatic erythrocytes,calculated micronucleus rate,micronucleus rate expressed in parts per thousand,and cal-culated the total proportion of red blood cells and red cells. Results 24 h after oral administration,the bone marrow micro-nucleus incidence of low,medium,high - dose group were 1. 92‰,1. 58‰,1. 83‰,respectively,compared with the vehicle control group(1. 75‰),there had no significant differences. But there were very significant differences(P ﹤ 0. 01)between it and positive control group(23. 92‰). After gavage for 48 h,the incidence of bone marrow of low,medium and high dose group were 1. 75‰,1. 58‰,1. 50‰,respectively,and vehicle control group(1. 83‰)had no significant difference,but had a very significant difference(P ﹤ 0. 01)compared with positive control group(21. 83‰). Conclusion Under the ex-perimental conditions,the result of micronucleus test of the right - handed rabeprazole sodium administration orally in mice was negative.
