新型特异性环氧合酶-2抑制剂对胎鼠中脑细胞增殖和分化的影响  

The Effect on Differentiation and Growth of Rat Embryo Micromass for Ia-10 and Ib-10:a New Type of Selective Inhibitor of Cyclooxygenase-2

作　　者：董延生[1,2] 刘密凤 李美英[2] 彭双清[1,2] 仲伯华[2] 

机构地区：[1]军事医学科学院疾病预防与控制研究所,北京100071 [2]军事医学科学院毒物药物研究所,北京100850 [3]不详

出　　处：《解放军药学学报》2009年第2期97-100,共4页Pharmaceutical Journal of Chinese People's Liberation Army

摘　　要：目的早期评价新型环氧合酶-2(cyclooxygenase-2,COX-2)抑制剂Ia-10及Ib-10潜在的生殖毒性。方法原代微团培养法培养大鼠胚胎中脑神经细胞,采用中性红吸收法和微团集落计数法,分别观察化合物Ia-10、Ib-10、已上市COX-2抑制剂赛来昔布以及生殖毒性阳性对照药羟基脲暴露后对细胞增殖和分化的影响,计算受试物对中脑神经细胞微团的半数增殖抑制浓度(50%inhibition of cell viability,IV50)和半数分化抑制浓度(50%inhibition of cells differentiation,ID50),并根据IV50与ID50的比值R来评价化合物的潜在生殖毒性(R>2.0,化合物具有潜在生殖毒性;R<2.0,化合物无潜在生殖毒性)。结果化合物Ia-10对中脑神经细胞微团的IV50为31.48μg.mL-1,ID50为8.76μg.mL-1(R=3.59);化合物Ib-10的IV50为35.46μg.mL-1,ID50为23.55μg.mL-1(R=1.51);赛来昔布的IV50为28.89μg.mL-1,ID50为36.55μg.mL-1(R=0.79);阳性药羟基脲的IV50为6.64μg.mL-1,ID50为2.52μg.mL-1(R=2.63)。结论根据R值进行判断,阳性药物羟基脲具有生殖毒性,赛来昔布无潜在的生殖毒性;化合物Ia-10具有潜在的生殖毒性,而化合物Ib-10无潜在生殖毒性,提示具有良好的市场开发前景。Aim To evaluate the development toxicity of a new type of inhibitor of cyclooxygenase-2：Ia-10 and Ib-10 in the early period. Methods Using rat embryo micromass cultures of midbrain by means of micromass counting and neutral red uptaking, we detected how cell differentiation and growth was inhibited by different drug concentrations of compound Ia-10,Ib-10,eeleeoxin and hydroxycarbamide. Then we calculated the semi-concentration of inhibition variability （ IV50 ） and inhibition differentiation （ ID50 ）, and the R value （ IV50/ID50 ）. Based on R value, we evaluated the reproduction toxicity of drugs （ If R 〉 2.0, compounds have potential reproduction toxicity; if R 〈 2.0, compounds have no potential reproduction toxicity）. Results The IV50 and ID50 of compound Ia-10 were 31.48μg·mL^-1 and 8. 76μg·mL^-1（ R =3.59）, those of compound Ib-10 were 35. 46μg·mL^-1 and 23. 55μg·mL^-1 （ R = 1.51 ） ; those of celecoxin were 28.89μg·mL^-1 and 36.55μg·mL^-1 （ R = 3.59）, those of hydroxycarbamide were 6.64 μg·mL^-1 and 2. 52μg·mL^-1 （ R = 3.59 ）. Conclusion According to R, positive drug hydroxycarbamide has potential reproductive toxicity, celecoxin has not, and compound Ia-10 has potential reproductive toxicity while compound Ib-10 has not. The data imply that compound Ib-10 has a better prospect for development and marketing.

关 键 词：COX-2抑制剂 微团培养 生殖毒性 致畸性 

分 类 号：R965[医药卫生—药理学]