复方感冒合剂对孕鼠胚胎发育毒性实验研究
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摘要
目的:
为了系统地研究复方感冒合剂的安全性,指导孕妇临床合理用药,本实验在SD孕鼠胚胎器官形成期给药,探讨复方感冒合剂对孕鼠的胚胎发育毒性。
方法:
将健康未交配的SD大鼠75只,雌性50只,雄性25只,于每天晚上18:00按照雌雄2:1的比例进行合笼交配,次日对雌鼠进行阴栓检查,对同笼未发现阴栓的雌鼠作阴道分泌物涂片,检查有无精子细胞,凡查见精子提示已交配成功。怀孕当天记为孕0天。将孕鼠随机分为5组,即复方感冒合剂高、中、低剂量组、阴性对照组和阳性对照组,(以下依次称为A、B、C、D、E组)。A、B、C组分别于大鼠受孕第7-16d连续灌胃给予复方感冒合剂相当于生药剂量13.0g/kg、6.5g/kg、3.3g/kg;同期D组给予等剂量的生理盐水;阳性对照组给予等剂量复方盐酸伪麻黄碱缓释胶囊,即新康泰克(按300mg伪麻黄碱/kg孕鼠体重算),给药体积均为10ml/kg。于妊娠第0天开始,每3天称一次孕鼠的体重,观察药物对孕鼠体重的影响,并跟据体重变化调整给药剂量。所有孕鼠在受孕第20天处死,进行胚胎毒性效应研究。记录每只孕鼠子宫胎盘重量,子宫胎鼠胎盘总重。仔细检查并记录活胎数、死胎数和吸收胎数。逐一测量活胎鼠的体重、身长、尾长,并检查活胎外观有无异常。每窝50%的活胎鼠经茜素红和阿利新蓝骨骼双染后检查全身骨骼发育情况。50%活胎鼠用Bouin液浸泡后做内脏检查。
结果:
1.复方感冒合剂对孕鼠一般情况的影响
A、B、C组孕鼠给药后外观体征、行为活动、粪便性状没有观察到明显异常变化,三组孕鼠增重与D组比较,F=0.035,F_(0.05(3,36))=2.77,F0.05,差异无统计学意义。E组孕鼠给药后第2天开始出现活动和饮食减少,大便干燥等变化,停药2天后开始恢复,与D组比较孕鼠体重增加明显减慢,t=3.763,t_(0.05)(18)=2.101,t_(0.01)(18)=2.878,t>t_(0.01)(18),P<0.01,差异有显著性意义。
2.复方感冒合剂对孕鼠生殖能力的影响
A、B、C各组孕鼠子宫胎盘重量与D组比较,F=0.026,F_(0.05(3,36))=2.77,F0.05,差异无统计学意义。A、B、C各组孕鼠子宫胎鼠胎盘总重与D组比较,F=0.00054,P>0.05,差异无统计学意义。A、B、C各组孕鼠吸收胎数、活胎数、死胎数与D组比较,X~2=3.9,X_(0.05)~2(6)=12.95,X~20.05,差异无统计学意义。E组孕鼠子宫胎盘重量、子宫胎鼠胎盘总重明显降低,与D组比较,t值分别为3.27、2.945,均大于t_(0.01)(18)=2.878,P<0.01,差异有显著性意义。E组活胎数减少,吸收胎和死胎数增多,与D组比较,X~2=11.9,X_(0.05)~2(2)=5.99,X_(0.01)~2(2)=9.21,X~2>X_(0.01)~2(2),P<0.01,差异有显著性意义。
3.复方感冒合剂对胎鼠生长发育的影响
A、B、C组胎鼠的体重与D组比较t值分别为:1.588、-1.716、1.094,体长与D组比较t值分别为:0.883、0、0.413,尾长与D组比较,t值分别为:1.626、1.186、1.140,以上结果所对应的P值均大于0.05,差异无统计学意义。E组与D组比较胎鼠的体重明显降低,体长和尾长明显缩短,与D组比较,t值分别为3.20、3.491、3.123,所对应的P值均小于0.01,差异有显著性意义。
4.复方感冒合剂对胎鼠外观的影响
身体外形异常表现为露脑、额裂、脐疝、腹裂、畸形足、短尾、无尾等。A、B、C、D、E各组胎鼠均未见露脑、额裂、腹裂、畸形足、无尾等外观变化。脐疝、短尾等变化的总发生率分别为:A组:2.44%;B组:2.30%;C组:1.16%;D组:2.22%;E组:14.86%。A、B、C组与D组比较,X~2=2.27,X_(0.05)~2(3)=7.81,X~20.05,差异无统计学意义。E组与D组比较,X~2=-5.73,X_(0.05)~2(1)=3.84,X~2>X_(0.05)~2(1),P<0.05,差异有统计学意义。
5.复方感冒合剂对胎鼠骨骼的影响
A、B、C组胎鼠骨骼总变异及畸形率与D组比较,X~2=0.34,X_(0.05)~2(3)=7.81,X~20.05,差异无统计学意义。E组胎鼠除有波状肋和骨骼发育迟缓外,还发现较多骨骼畸形,表现为椎体分离、椎体分裂(椎骨椎体中心软骨分裂)、肋缺失、颈肋、腰肋等。其总变异及畸形率与D组比较,X~2=7.27,X_(0.05)~2(1)=3.84,X_(0.01)~2(1)=6.63,X~2>X_(0.01)~2(1),P<0.01,差异有显著性意义。
6.复方感冒合剂对胎鼠内脏的影响
A、B、C组胎鼠散在出现胸腺颈部残留、肾盂积水等内脏畸形,三组总畸形率与D组比较,X~2=1.22,X_(0.05)~2(3)=7.81,X~20.05,差异无统计学意义。E组胎鼠出现较多内脏畸形,如胸腺颈部残留、突眼、肾盂积水、脑室扩张等,总畸形率与D组比较,X~2=6.97,X_(0.05)~2(1)=3.84,X_(0.01)~2(1)=6.63,X~2>X_(0.01)~2(1),P<0.01,差异有显著性意义。
结论:
综合以上结果发现:在本实验室条件下,复方感冒合剂高、中、低剂量在孕鼠致畸敏感期灌胃给药,各剂量均无明显母体毒性、胚胎毒性和致畸作用,且在实验剂量范围内,复方感冒合剂未呈现剂量反应关系。通过阴性对照组的结果可以发现在无任何外因干预的情况下胎鼠也有出现一定比例变异和畸形的可能。阳性对照组出现明显的母体毒性、胚胎毒性和致畸作用。因此,为避免对胚胎发育产生毒性作用,建议妊娠期间慎重选择感冒药,严格掌握用药剂量并遵循配伍原则。
Objective:
In order to study systematically the security of compound prescription cold mixture, and to guide clinical rational drug use in pregnant women, SD pregnant rats were administered during their embryos organ formation period in this experiment to explore the compound prescription cold mixture' s toxicity for embryonic developmental of pregnant rats.
Method:
Healthy SD rats 75 which did not mate female 50, male 25, at 18: 00 every night in accordance with the ratio of 2: 1 for male and female cage mate together, the next day to carry out female vaginal suppository for inspection, on the same cage did not find the female vaginal suppository for vaginal secretion smear to check for sperm cells, where the investigation has been prompted to see the mating success of sperm. the day of Pregnancy was recorded as 0 days of pregnant. The pregnant rats were randomly divided into 5 groups, namely, a compound prescription cold mixture high, medium and low dose, negative control group and positive control group, (respectively referred to as A, B, C, D, E group). A, B, C group respectively in the pregnancy in 7-16 days gavage forcompound prescription cold mixtureto give the pregnant rats 13.0g/kg、6. 5g/kg、3. 3g/kg. D group, in the same period gaven the same doses of normal saline. And the positive control group were gaven same dose of compound pseudoephedrine hydrochloride sustained-release capsules, that is, the new Kangtaike (at 300mg pseudoephedrine / kg body weight count).The medicine volume was 10ml/kg. In the pregnancy 0th day start, every 3 days to check one time the pregnant rats body weight, observe the influence of the medicine for the pregnant rats body weight, and according to the body weight to adjust the medicament dose . All pregnant rats be killed in the pregnancy 20th day , to conduct the embryo poisonous effect research. And to record each pregnant rat uterus placental weight, and the total weight of the uterus and placenta and fetal rat.To inspect and record the live embryo number, the dead embryo number, and the absorption embryo number carefully. To measure live weight、body length and tail length of fetal rat, and to check whether there were abnormal appearance of live births. Each nest 50% live embryo rats double dye after the sodium alizarinsulfonate and the Aly new blue skeleton to inspect the whole body skeleton growth situation. 50% live embryo rats to were given the internal organs inspection after the Bouin fluid immersion.
Result:
1. the effects of compound prescription cold mixture to pregnant rats reproductive capacity
The appearance of signs, behavior activity, stool traits of A, B, C group pregnant rats after were administered not observed in apparent anomalies, three groups of pregnant rats weight gain compared with the D group,F=0. 035, F_(0.05(3,36)) =2. 77, F0. 05, there was no significant difference. E group of pregnant rats arise activities and diet began to decrease、feces become dry after the second days of administration , such as changes in 2 days after discontinuation of treatment began to recover, compared with the D group pregnant rats' weight gain significantly slower , t=3. 763, t_(0.05)(18)=2. 101, t_(0.01)(18)=2. 878, t>t_(0.01)(18), P < 0. 01,
The difference was significant.
2. the effects of compound prescription cold mixture to pregnant rats reproductive capacity
The utero placental weight of A, B, C pregnant rats compared with D group , F=0. 026, F_(0.05(3, 36))=2. 77, F0. 05, there was no significant difference. the placenta in fetal rat uterine total weight of A, B, C pregnant rats in each group compared with D group, F=0. 00054, P>0. 05, there was no significant difference. the live embryo number, the dead embryo number, and the absorpted embryo number of A, B, C pregnant rats in each group compared with D group, X~2=3. 9, X_(0.05)~2(6)=12. 9, 5 X~20. 05, there was no significant difference. the weight of placenta and uterine of pregnant rats、total weight of the uterine placenta in fetal rats of E group significantly decreased compared with D group, t numeric were 3.27,2.945, were greater than t_(0.01)(18)=2. 878 , t>t_(0.01)(18),P <0.01 , the difference was significant.the live embryo number, the dead embryo number, and the absorpted embryo number of E group compared with D group,X~2=11. 9, X_(0.05)~2(2) =5.99, X_(0.01)~2(2) =9.21, X~2>X_(0.01)~2(2) , P <0. 01, The difference was significant.
3. the effects of compound prescription cold mixture to fetal rats growth and development
The body weight of fetal rats of A, B, C group compared with the D group , t numeric were as follows: 1. 588、-1. 716、1. 094, body Length compared with the D group, t numeric were as follows: 0.883、0、0.413, Tail length compared with the D group, t numeric were as follows: 1.626、1.186、1.140，These results corresponding to P numeric greater than 0.05, the difference was not statistically significant. E group compared with D group body weight of fetal rats reduced significantly , body length and tail length was significantly shorter , t numeric were 3.20、3.491、3.123, Corresponding to P <0. 01,The difference was significant.
4. the effects of compound prescription cold mixture to fetal rats appearance
Physical appearance differences usually are exposed brain, forehead split, umbilical hernia, abdominal dehiscence, foot deformities, a short tail, no tail and so on . A, B, C, D, E in each group were not exposed brain, forehead split, abdominal dehiscence, foot deformities, a short tail, no tail changes in appearance. umbilical hernia, a short tail, such as changes in the overall incidence rates were: A: 2.44%; B: 2.30%; C: 1.16%; D: 2.22%; E: 14.86%. Comparison of A, B, C group and D group, X~2=2.27 , X_(0.05)~2(3) =7. 81, X~20. 05, there was no significant difference. E group compared with the D group, X~2=-5. 73 , X_(0.05)~2(1) =3. 84, X~2>X_(0.05)~2(1), P<0. 05, the difference was statistically significant.
5. the effects of compound prescription cold mixture to fetal rats bone
The total variation and malformation rate of fetal rat bone of A, B, C group compared with D group, X~2=0. 34, X_(0.05)~2(3)=7.81, X~20. 05, there was no significant difference. The fetal rats of E group in addition to have wavy ribs and skeletal growth retardation, but also found that there were more skeletal deformities, showed vertebral separation, split vertebral body (Split vertebrae vertebral cartilage center), missing rib, cervical rib, lumbar costatum. The total variation and malformation rate compared with D group, X~2=7. 27, X_(0.05)~2(1)=3. 84, X_(0.01)~2(1)=6. 63, X~2>X_(0.01)~2(1),P<0. 01,The difference was significant.
6. the effects of compound prescription cold mixture to fetal rats organs
A, B, C group scattered emerged residual visceral malformation , such as thymus residues in the sneck, hydronephrosis, the rate of the total malformation of three groups compared with D group, X~2=1.22 , X_(0.05)~2(3)=7.81, X~20. 05, there was no significant difference. E group occurred more frequently visceral malformations of fetal rats , such as thymus in the neck ,exophthalmos, hydronephrosis, ventricular expansion, etc. the total malformation rate compared with the D group, X~2=6. 97, X_(0.05)~2(1)=3. 84, X_(0.01)~2(1)=6. 63, X~2>X_(0.01)~2(1), P<0. 05, The difference was significant.
Conclusion:
The results above showed that : in the laboratory conditions, the compound prescription cold mixture of high, medium and low doses have been gavaged to pregnant rats in teratogenic sensitive period, the dose had no significant maternal toxicity, embryo toxicity and teratogenic effects, and in experimental dose range, compound prescription cold mixture haven't appeared in a dose-response relationship . But positive control group have appeared significant maternal toxicity , embryo toxicity and teratogenic effect. Thus, in order to avoid the effects of embryo development toxicity ,it is recommended to choose cold medicine carefully during pregnancy , strictly dose of drugs and adhere to the principle of compatibility.
为了系统地研究复方感冒合剂的安全性,指导孕妇临床合理用药,本实验在SD孕鼠胚胎器官形成期给药,探讨复方感冒合剂对孕鼠的胚胎发育毒性。
方法:
将健康未交配的SD大鼠75只,雌性50只,雄性25只,于每天晚上18:00按照雌雄2:1的比例进行合笼交配,次日对雌鼠进行阴栓检查,对同笼未发现阴栓的雌鼠作阴道分泌物涂片,检查有无精子细胞,凡查见精子提示已交配成功。怀孕当天记为孕0天。将孕鼠随机分为5组,即复方感冒合剂高、中、低剂量组、阴性对照组和阳性对照组,(以下依次称为A、B、C、D、E组)。A、B、C组分别于大鼠受孕第7-16d连续灌胃给予复方感冒合剂相当于生药剂量13.0g/kg、6.5g/kg、3.3g/kg;同期D组给予等剂量的生理盐水;阳性对照组给予等剂量复方盐酸伪麻黄碱缓释胶囊,即新康泰克(按300mg伪麻黄碱/kg孕鼠体重算),给药体积均为10ml/kg。于妊娠第0天开始,每3天称一次孕鼠的体重,观察药物对孕鼠体重的影响,并跟据体重变化调整给药剂量。所有孕鼠在受孕第20天处死,进行胚胎毒性效应研究。记录每只孕鼠子宫胎盘重量,子宫胎鼠胎盘总重。仔细检查并记录活胎数、死胎数和吸收胎数。逐一测量活胎鼠的体重、身长、尾长,并检查活胎外观有无异常。每窝50%的活胎鼠经茜素红和阿利新蓝骨骼双染后检查全身骨骼发育情况。50%活胎鼠用Bouin液浸泡后做内脏检查。
结果:
1.复方感冒合剂对孕鼠一般情况的影响
A、B、C组孕鼠给药后外观体征、行为活动、粪便性状没有观察到明显异常变化,三组孕鼠增重与D组比较,F=0.035,F_(0.05(3,36))=2.77,F
2.复方感冒合剂对孕鼠生殖能力的影响
A、B、C各组孕鼠子宫胎盘重量与D组比较,F=0.026,F_(0.05(3,36))=2.77,F
3.复方感冒合剂对胎鼠生长发育的影响
A、B、C组胎鼠的体重与D组比较t值分别为:1.588、-1.716、1.094,体长与D组比较t值分别为:0.883、0、0.413,尾长与D组比较,t值分别为:1.626、1.186、1.140,以上结果所对应的P值均大于0.05,差异无统计学意义。E组与D组比较胎鼠的体重明显降低,体长和尾长明显缩短,与D组比较,t值分别为3.20、3.491、3.123,所对应的P值均小于0.01,差异有显著性意义。
4.复方感冒合剂对胎鼠外观的影响
身体外形异常表现为露脑、额裂、脐疝、腹裂、畸形足、短尾、无尾等。A、B、C、D、E各组胎鼠均未见露脑、额裂、腹裂、畸形足、无尾等外观变化。脐疝、短尾等变化的总发生率分别为:A组:2.44%;B组:2.30%;C组:1.16%;D组:2.22%;E组:14.86%。A、B、C组与D组比较,X~2=2.27,X_(0.05)~2(3)=7.81,X~2
5.复方感冒合剂对胎鼠骨骼的影响
A、B、C组胎鼠骨骼总变异及畸形率与D组比较,X~2=0.34,X_(0.05)~2(3)=7.81,X~2
6.复方感冒合剂对胎鼠内脏的影响
A、B、C组胎鼠散在出现胸腺颈部残留、肾盂积水等内脏畸形,三组总畸形率与D组比较,X~2=1.22,X_(0.05)~2(3)=7.81,X~2
结论:
综合以上结果发现:在本实验室条件下,复方感冒合剂高、中、低剂量在孕鼠致畸敏感期灌胃给药,各剂量均无明显母体毒性、胚胎毒性和致畸作用,且在实验剂量范围内,复方感冒合剂未呈现剂量反应关系。通过阴性对照组的结果可以发现在无任何外因干预的情况下胎鼠也有出现一定比例变异和畸形的可能。阳性对照组出现明显的母体毒性、胚胎毒性和致畸作用。因此,为避免对胚胎发育产生毒性作用,建议妊娠期间慎重选择感冒药,严格掌握用药剂量并遵循配伍原则。
Objective:
In order to study systematically the security of compound prescription cold mixture, and to guide clinical rational drug use in pregnant women, SD pregnant rats were administered during their embryos organ formation period in this experiment to explore the compound prescription cold mixture' s toxicity for embryonic developmental of pregnant rats.
Method:
Healthy SD rats 75 which did not mate female 50, male 25, at 18: 00 every night in accordance with the ratio of 2: 1 for male and female cage mate together, the next day to carry out female vaginal suppository for inspection, on the same cage did not find the female vaginal suppository for vaginal secretion smear to check for sperm cells, where the investigation has been prompted to see the mating success of sperm. the day of Pregnancy was recorded as 0 days of pregnant. The pregnant rats were randomly divided into 5 groups, namely, a compound prescription cold mixture high, medium and low dose, negative control group and positive control group, (respectively referred to as A, B, C, D, E group). A, B, C group respectively in the pregnancy in 7-16 days gavage forcompound prescription cold mixtureto give the pregnant rats 13.0g/kg、6. 5g/kg、3. 3g/kg. D group, in the same period gaven the same doses of normal saline. And the positive control group were gaven same dose of compound pseudoephedrine hydrochloride sustained-release capsules, that is, the new Kangtaike (at 300mg pseudoephedrine / kg body weight count).The medicine volume was 10ml/kg. In the pregnancy 0th day start, every 3 days to check one time the pregnant rats body weight, observe the influence of the medicine for the pregnant rats body weight, and according to the body weight to adjust the medicament dose . All pregnant rats be killed in the pregnancy 20th day , to conduct the embryo poisonous effect research. And to record each pregnant rat uterus placental weight, and the total weight of the uterus and placenta and fetal rat.To inspect and record the live embryo number, the dead embryo number, and the absorption embryo number carefully. To measure live weight、body length and tail length of fetal rat, and to check whether there were abnormal appearance of live births. Each nest 50% live embryo rats double dye after the sodium alizarinsulfonate and the Aly new blue skeleton to inspect the whole body skeleton growth situation. 50% live embryo rats to were given the internal organs inspection after the Bouin fluid immersion.
Result:
1. the effects of compound prescription cold mixture to pregnant rats reproductive capacity
The appearance of signs, behavior activity, stool traits of A, B, C group pregnant rats after were administered not observed in apparent anomalies, three groups of pregnant rats weight gain compared with the D group,F=0. 035, F_(0.05(3,36)) =2. 77, F
The difference was significant.
2. the effects of compound prescription cold mixture to pregnant rats reproductive capacity
The utero placental weight of A, B, C pregnant rats compared with D group , F=0. 026, F_(0.05(3, 36))=2. 77, F
3. the effects of compound prescription cold mixture to fetal rats growth and development
The body weight of fetal rats of A, B, C group compared with the D group , t numeric were as follows: 1. 588、-1. 716、1. 094, body Length compared with the D group, t numeric were as follows: 0.883、0、0.413, Tail length compared with the D group, t numeric were as follows: 1.626、1.186、1.140，These results corresponding to P numeric greater than 0.05, the difference was not statistically significant. E group compared with D group body weight of fetal rats reduced significantly , body length and tail length was significantly shorter , t numeric were 3.20、3.491、3.123, Corresponding to P <0. 01,The difference was significant.
4. the effects of compound prescription cold mixture to fetal rats appearance
Physical appearance differences usually are exposed brain, forehead split, umbilical hernia, abdominal dehiscence, foot deformities, a short tail, no tail and so on . A, B, C, D, E in each group were not exposed brain, forehead split, abdominal dehiscence, foot deformities, a short tail, no tail changes in appearance. umbilical hernia, a short tail, such as changes in the overall incidence rates were: A: 2.44%; B: 2.30%; C: 1.16%; D: 2.22%; E: 14.86%. Comparison of A, B, C group and D group, X~2=2.27 , X_(0.05)~2(3) =7. 81, X~2
5. the effects of compound prescription cold mixture to fetal rats bone
The total variation and malformation rate of fetal rat bone of A, B, C group compared with D group, X~2=0. 34, X_(0.05)~2(3)=7.81, X~2
6. the effects of compound prescription cold mixture to fetal rats organs
A, B, C group scattered emerged residual visceral malformation , such as thymus residues in the sneck, hydronephrosis, the rate of the total malformation of three groups compared with D group, X~2=1.22 , X_(0.05)~2(3)=7.81, X~2
Conclusion:
The results above showed that : in the laboratory conditions, the compound prescription cold mixture of high, medium and low doses have been gavaged to pregnant rats in teratogenic sensitive period, the dose had no significant maternal toxicity, embryo toxicity and teratogenic effects, and in experimental dose range, compound prescription cold mixture haven't appeared in a dose-response relationship . But positive control group have appeared significant maternal toxicity , embryo toxicity and teratogenic effect. Thus, in order to avoid the effects of embryo development toxicity ,it is recommended to choose cold medicine carefully during pregnancy , strictly dose of drugs and adhere to the principle of compatibility.
引文
[1] 唐贵忠.我国人口出生缺陷状况及干预措施的分析[J].中华妇幼保健,2001,16(7):408-409
[2] Suresh L,RadfarL. Pregnancy and lactation[J]. Oral SurgOralMed OralPatholOralRadiolEndod,2004,97: 72
[3] 刘娜,孙峰,胡茂德.妊娠期禁用药物与致畸评价[J].医师进修杂志,1999,2:60
[4] 胡渝华 发育毒性与致畸作用 见王心如主编 毒理学基础 人民卫生出版社,2003 155-168.
[5] 张均田 现代药理实验方法[M]北京医科大学,中国协和医科大学联合出版社1997:1949-1969
[6] 郄建坤.西替利嗪/伪麻黄碱[J].国外医学·药学分册,2002,29(4):252.
[7] 孙晓英 张振军 边学峰 陈庆 于燕.伪麻黄碱对大鼠致畸作用研究癌变畸变突变检测研究2006,1,18(1):68-70
[8] Wheless JW, Neto W, Wang S, EPMN-105 Study Group. Topiramate,carbamazepine, and valproate monotherapy: double-blind comparison in children with newly diagnosed epilepsy. J Child Neurol, 2004, 19:135-141.
[9] 李勇,张天宝编发育毒理学研究方法和实验技术.北京:北京医科大学出版社,2002:186-187
[10] 中华人民共和国国家标准(GB15193.14-94):致畸实验
[11] 甘卉芳,李百祥等.传统致畸试验中发育迟缓评价指标的探讨.中华劳动卫生职业病杂志,2001,19(2):137-138.
[12] 黄醒华.孕期药物动力学的改变[J]. 中国实用妇科与产科杂志,1999,14(5):273.
[13] 杨怀恭,孕期用药与出生缺陷.实用妇产科杂志,1989,5(1):3
[14]Metneki J,Puho E,Czeizel A E. Maternal diseases and isola tedorofacial clefts in Hungary. Birth Defects Research Part A, 2005,73(9): 617-623.
[15] 董淑萍,现代中西医结合杂志Modern Journal of Integrated Traditional Chinese and Western Medicine 2007 Jan , 16(3): 361-362
[16] 杜惠兰,妊娠期中西药物用药禁忌.人民卫生出版社 2007,8 17.
[17] 吕怡芳,王秋晶,杨世杰.薄荷油对小白鼠终止妊娠作用的初步观察.白求恩医科大学学报,1989,15(5):455-458
[18] 杨世杰,吕怡芳,王秋晶.等. 薄荷油终止家兔早期妊娠及其机理的初探.中草药,1991,22(10):454-457
[19] 苗明三,杨桂芳.中药的三致作用.河南中医药学刊,2002,17(1):2
[20] 卞如濂,杨秋火,任熙云,等.荆芥油的药理研究.浙江医科大学学报 1981;10(5):29
[21] 山原条二.荆芥的镇痛和消炎作用.国外药学.植物药分册1981:2(2):32
[22] 郝莉萍,于树劳.荆、防、柴、菊抑制流感病毒的实验研究.人民军医1992;35(11):49
[23] 张丽,周勇,马学清,等.防风多糖JBO-6对荷瘤小鼠免疫功能的影响及抗肿瘤作用的实验研究[J]中国实验临床免疫学杂志,1997,9(5):53-56
[24] 李莉,周勇,张丽,等.防风多糖IL-2体外对小鼠NK、LAK细胞活性的影响及体内抗移植瘤生长的实验研究[J]北京中医药大学学报,1997,20(5):39-4 0
[25] 马学清,周勇,严宣佐,等.中药多糖的免疫增强作用[J]中国实验临床免疫学杂志,1996,8(2):40-43
[26] 薛宝云,李文,李丽,等.防风色原酮甙类成分的药理活性研究[J]
[27] 唐荣江,闵照华,徐诚愈-防风的药理实验研究[J]中药通报,1988,13(6):45
[28] 丁树利,朱兆仪 紫苏属植物研究进展国外医药·植物药分册,1994;9(1):4
[29] 王静珍,陶上乘,邢永春,等紫苏与白苏药理作用的研究 中国中药杂志,1997;22(1):48
[30] 陈新俊 紫苏的临床应用时日本对紫苏抗炎和抗过敏的研究 时珍国药研究,1998;9(2):131
[31] Uede H , Yamazaki M. Inhibition of tumor necrosis factor2α pro2 duction by orally administering a Perilla leaf extracts[J]. Biosci Biotech Biochem,1997,61(8):1292.
[32] 崔树玉,薛原,杨建莉等.斑斓更研究进展[J].中草药,2001,32(7):670-671
[33] 刘盛,陈万生,乔传卓等.不同种质板蓝根和大青叶的抗甲型流感病毒作用[J].第二军医大学学报,2000,21(3):204.
[34] 陈奇.中药药理研究方法学.北京:人民卫生出版社,1993.378
[35] 许启泰,杜钢军,林海红,板蓝根醇沉物的药理作用.中国医院药学杂志2003年第23卷第10期587-589
[36] 卫琮玲,闫杏莲,板蓝根的抗炎作用.开封医专学报2000年第19卷第4期53-54
[37] 何丽媛 柴胡静脉乳剂的解热、镇痛作用.实用药物与临床2007年第10卷第5期270-272
[38] 安玉明,接传胤,祝世伟.柴胡的研究进展[J].人参研究,2001,13(1):11-13.
[39] 周玉皆,鲁珊,王志英等.葛根素对COPD大鼠气道炎症及气道重塑作用的研究.医学临床研究 2007年8月第24卷第8期:1249-1251
[40] 江苏医学院 中药大辞典 上海:上海科学技术出版社,1999:1077
[41] 国家中医药管理局。中华本草(下),上海:上海科学技术出版社,1998:2159
[42] Decker J et al. C.A. 1983; 99: 104z81C
[43] Tsitsa TzardiE et al. C. A1991; 114: 139650C
[44] Ji-nian Fang et al.phytochemistry 1990; 29 (9): 3019
[45] 张国升,凡明月,张佳美,方方,蔡艳丽等.芦根多糖的研究.中国医药学报.2002,17(4):250
[46] Janine E. Polifka,J.M. Friedman. Medical genetics: 1. Clinical teratology in the age of genomics. Canadian Medical Association or its licensors, 2002, 167:265-273.
[47] 吕伯钦等译 实验毒理学基础.北京人民卫生出版社,1987,1
[1] 唐贵忠 我国人口出生缺陷状况及干预措施的分析[J] 中华妇幼保健,2001,16(7):408-409
[2] 李希新,张恒齐、论妊娠禁忌药在妊娠期的应用、山东中医杂志,1999,18(8):368
[3] 张颂,张宗禹,石其贤,等、阿魏的终止妊娠作用、中草药,1991,22(10):458-459
[4] 柳红芳,高学敏、蒲黄水煎液对小鼠妊娠影响的实验研究、中药药理与临床,1994,10(2):26-29
[5] 国家中医药管理局《中华本草》编委会、中华本草(第一册)、上海:上海科学技术出版社,1995、235
[6] 宋树立、川牛膝水煎液影响小鼠妊娠的实验研究、中国医药学报,1994, 9(4):40
[7] 李仪奎,姜名瑛、中药药理学、北京:中国中医药出版社,1992、86
[8] 郭胜民,车锡平,范晓雯、怀牛肤皂苷A对离体大鼠子宫兴奋作用机理的研究、西安医科大学学报,1997,18(4):473
[9] 王世祥,车锡平、怀牛肤总皂苷对离体大鼠子宫的兴奋作用及机理研究、西北药学杂志,1996,11(4);160
[10] 朱和、牛肤总皂甙对动物子宫平滑肌的作用、中草药,1987,18(4):17
[11] 马永明,刘恒,瞿颂义,等、芫花对未孕大鼠离体子宫平滑肌条作用的研究、中国中药杂志,1998,23(4):429
[12] 吕富华,吴熙瑞,洪山海,等、益母草的药理研究(对子宫作用的第1次报告)、中华医学杂志,1954:40(9):699
[13] 潘思源,常英,魏路雪,等、茺蔚子总碱和水苏碱收缩离体小鼠子宫的比较、中草药,1998,29(10):687
[14] 何功倍,张世芳,王怀真,等、重楼排草对家兔、豚鼠、大鼠、小鼠 子中的作用、中成药研究,1986,(10):28
[15] 雎大簋,吕忠智,李淑惠、九里香化学及抗生育作用研究概况、中草药,1994.25(8):436
[16] 广西祟左县人民医院、中草药贯众注射液对子宫收缩临床应用的初步观察、中草药通讯,1970,(5):35
[17] 陈琦、贯众抗生育有效部分的药理研究、天津医药,1980,(8):488
[18] 高南南,于澍仁,冯毓秀,等、泽兰两个品种对小鼠离体子宫平滑肌的作用、基层中药杂志,1995,9(3):34
[19] 李卫民,高英,吕振兰,等、中草药抗生育研究、中国医药科技出版社,1993、342
[20] 周铭东,江燕,赵翠兰,等、扶桑花中石油醚溶物的组分研究及抗生育初探、云南中药杂志,1997,18(2):33
[21] 江燕,赵翠兰,李开源,等、扶桑花石油醚溶物(HR-1)对小鼠离体子宫兴奋作用的机理研究.云南中医中药杂志,1998,19(1):25
[22] 姜枫勤,刘世明,李克勤,等、逐瘀清官冲剂药效学研究山东中医药大学学报,1997,21(3):218
[23] 马永明,刘恒,瞿颂义,等、乌梅对大鼠离体子宫平滑肌条运动的影响及其机理探讨、中国中西医结合杂志,1998,(6):18
[24] 杨东焱,马永明,田治峰,等、乌梅对未孕和早孕大鼠子宫平滑肌电活动的影响及其机理探讨、成药,2000,22(12):850
[25] 闫升,乔国芳,刘志峰,等、当归油对大鼠离体子宫平滑肌收缩功能的影响、中草药,2000,31(8):606
[26] 李卫民,高英,吕振兰.等、中草药抗生育研究、北京:中国医药科技出版社,1993、342
[27] 吴克让、续断的药理作用、浙江中医学院学报,1983,7(增刊):2
[28] 龚小健,吴知行,陈真,等、川续断DA303对大鼠子宫的作用、中国药科大学学报,1996,27(1):48
[29] 吴佩君,陈活彝,吴子斌,等、天花粉蛋白对小鼠胚早期发育的影响、 生殖与避孕,1994,14(1):8-12
[30] 肖庆慈,毛小平.赵霞,等、妊娠禁忌药-斑蝥的部分药理研究、云南中医学院学报,2000,23(1):10
[31] 国家中医药管理局编委会、中华本草(第九册)、上海:上海科学技术出版社,1999、27-28
[32] 雷载权,张廷模、中华临床中药学、北京:人民卫生出版社、1988、141
[33] 秦伯未,张赞臣,徐福民,等、妊娠禁忌药的初频囊理、上海中医药杂志,1956;二月号:27-36
[34] 田新村、浅探中药妊娠禁忌、新疆中医药,1989,(4):44
[35] 国家中医药管理局编委会、中华本草(第一册)、上海:上海科学技术出版社,1999、249
[36] 郁加凡,楼星湟、妊娠期用药的临床体会、浙江中医学院学报,1982;(3): 24
[37] 杜惠兰,妊娠期中西药物用药禁忌.人民卫生出版社 2007,8: 25.
[38] 何绍奇、关于半夏用于妊娠恶阻的问题、广西中医药,1983:6(3):34
[39] 郭胜民,车锡平,范晓雯、怀牛膝皂甙A的抗生育作用和对离体子宫平滑肌的作用、西北药学杂志,1996,11(增刊)。46-49
[40] 朱和,车锡平、牛膝总皂苷对大鼠离体子宫兴奋作用机理的研究、中国药理学通报,1988,4(4):241
[41] 王本祥、现代中药药理学、天津:天津科学技术出版社,1997、905-906, 898-899,857-858,736-739,1263-1264
[42] 柳红芳,高学敏、蒲黄水煎液对小鼠妊娠影响的实验研究、中药药理与临床、1994,10(2):26-29
[43] 杨守业,何民,王岚,等、大黄对大白鼠妊娠和胚胎毒性研究、中国中西医结合杂志,1992,12(8):485
[44] 郑显理,罗连城,许树朴,等,妊娠期急性胰腺炎.天津医药杂志, 1966,(4):260
[45] 肖泓,肖庆慈,毛小平,等、地龙对妊娠影响之初探、云南中医学院虫类妊娠禁忌药的部分药理研究组,2000,(1):17-21
[46] 肖庆慈,毛小平,赵霞,等、妊娠禁用药-斑蝥的部分药理研究、云南中医学院虫类妊娠禁忌药的部分药理研究组,2000,(1):22-26
[47] 郭峰,李川生,周维登、天花粉对实验性肝癌腹水型的疗效观察及免疫机理的初步探讨、第二军医大学学报,1980,1(2):9-11
[48] 郭峰,李川生,刘潜心、天花粉抗实验性肝癌腹水免疫细胞变化观察、肿瘤,1986,6(6):274
[49] 郭峰,刘小平,徐瑛、天花粉对小鼠艾氏腹水癌的疗效和对红细胞周期的影响、中国中西医结合杂志,1998,18(1),35-37
[50] 毕黎琦,李洪军,张玉华、天花粉蛋白对黑色素瘤细胞凋亡及细胞周期的影响、中国中西医结合杂志,1998,18(1):35-37
[51] 包素珍,孙在典,张爱琴、中药蛇六谷对荷瘤小鼠S180抑瘤及细胞周期的影响、浙江中西医结合杂志,1999,9(3):162-163
[52] 包素珍,孙在典,张爱琴、蛇六谷诱导肿瘤细胞凋亡的实验研究、浙江中医杂志,1999,34(6):276
[53] 陈培丰,刘鲁明、中药蛇六谷抗癌活性及诱导癌细胞凋亡、中国中医基础学杂志,2000,6(9):30-32
[54] 陈国强、氧化砷诱导早幼粒细胞白血病细胞凋亡及其分子机制的初步研究、中华血液病杂志,1997,18(1):25
[55] 金恩波,姜名瑛,黄启福,等、中药十八反的药理研究、中成药研究,1982, (2):28
[56] 杨致礼,王佑之,吴成林,等、中药“十八反”在小白鼠上的毒性试验、甘肃农大学报,1982,(1):46
[57] 萧庆慈、中药十九畏的研究总结、云南中医学院学报,1998,21(增刊):1-3
[59] 凌一揆、中药学、上海:上海科学技术出版社、1984,12
[2] Suresh L,RadfarL. Pregnancy and lactation[J]. Oral SurgOralMed OralPatholOralRadiolEndod,2004,97: 72
[3] 刘娜,孙峰,胡茂德.妊娠期禁用药物与致畸评价[J].医师进修杂志,1999,2:60
[4] 胡渝华 发育毒性与致畸作用 见王心如主编 毒理学基础 人民卫生出版社,2003 155-168.
[5] 张均田 现代药理实验方法[M]北京医科大学,中国协和医科大学联合出版社1997:1949-1969
[6] 郄建坤.西替利嗪/伪麻黄碱[J].国外医学·药学分册,2002,29(4):252.
[7] 孙晓英 张振军 边学峰 陈庆 于燕.伪麻黄碱对大鼠致畸作用研究癌变畸变突变检测研究2006,1,18(1):68-70
[8] Wheless JW, Neto W, Wang S, EPMN-105 Study Group. Topiramate,carbamazepine, and valproate monotherapy: double-blind comparison in children with newly diagnosed epilepsy. J Child Neurol, 2004, 19:135-141.
[9] 李勇,张天宝编发育毒理学研究方法和实验技术.北京:北京医科大学出版社,2002:186-187
[10] 中华人民共和国国家标准(GB15193.14-94):致畸实验
[11] 甘卉芳,李百祥等.传统致畸试验中发育迟缓评价指标的探讨.中华劳动卫生职业病杂志,2001,19(2):137-138.
[12] 黄醒华.孕期药物动力学的改变[J]. 中国实用妇科与产科杂志,1999,14(5):273.
[13] 杨怀恭,孕期用药与出生缺陷.实用妇产科杂志,1989,5(1):3
[14]Metneki J,Puho E,Czeizel A E. Maternal diseases and isola tedorofacial clefts in Hungary. Birth Defects Research Part A, 2005,73(9): 617-623.
[15] 董淑萍,现代中西医结合杂志Modern Journal of Integrated Traditional Chinese and Western Medicine 2007 Jan , 16(3): 361-362
[16] 杜惠兰,妊娠期中西药物用药禁忌.人民卫生出版社 2007,8 17.
[17] 吕怡芳,王秋晶,杨世杰.薄荷油对小白鼠终止妊娠作用的初步观察.白求恩医科大学学报,1989,15(5):455-458
[18] 杨世杰,吕怡芳,王秋晶.等. 薄荷油终止家兔早期妊娠及其机理的初探.中草药,1991,22(10):454-457
[19] 苗明三,杨桂芳.中药的三致作用.河南中医药学刊,2002,17(1):2
[20] 卞如濂,杨秋火,任熙云,等.荆芥油的药理研究.浙江医科大学学报 1981;10(5):29
[21] 山原条二.荆芥的镇痛和消炎作用.国外药学.植物药分册1981:2(2):32
[22] 郝莉萍,于树劳.荆、防、柴、菊抑制流感病毒的实验研究.人民军医1992;35(11):49
[23] 张丽,周勇,马学清,等.防风多糖JBO-6对荷瘤小鼠免疫功能的影响及抗肿瘤作用的实验研究[J]中国实验临床免疫学杂志,1997,9(5):53-56
[24] 李莉,周勇,张丽,等.防风多糖IL-2体外对小鼠NK、LAK细胞活性的影响及体内抗移植瘤生长的实验研究[J]北京中医药大学学报,1997,20(5):39-4 0
[25] 马学清,周勇,严宣佐,等.中药多糖的免疫增强作用[J]中国实验临床免疫学杂志,1996,8(2):40-43
[26] 薛宝云,李文,李丽,等.防风色原酮甙类成分的药理活性研究[J]
[27] 唐荣江,闵照华,徐诚愈-防风的药理实验研究[J]中药通报,1988,13(6):45
[28] 丁树利,朱兆仪 紫苏属植物研究进展国外医药·植物药分册,1994;9(1):4
[29] 王静珍,陶上乘,邢永春,等紫苏与白苏药理作用的研究 中国中药杂志,1997;22(1):48
[30] 陈新俊 紫苏的临床应用时日本对紫苏抗炎和抗过敏的研究 时珍国药研究,1998;9(2):131
[31] Uede H , Yamazaki M. Inhibition of tumor necrosis factor2α pro2 duction by orally administering a Perilla leaf extracts[J]. Biosci Biotech Biochem,1997,61(8):1292.
[32] 崔树玉,薛原,杨建莉等.斑斓更研究进展[J].中草药,2001,32(7):670-671
[33] 刘盛,陈万生,乔传卓等.不同种质板蓝根和大青叶的抗甲型流感病毒作用[J].第二军医大学学报,2000,21(3):204.
[34] 陈奇.中药药理研究方法学.北京:人民卫生出版社,1993.378
[35] 许启泰,杜钢军,林海红,板蓝根醇沉物的药理作用.中国医院药学杂志2003年第23卷第10期587-589
[36] 卫琮玲,闫杏莲,板蓝根的抗炎作用.开封医专学报2000年第19卷第4期53-54
[37] 何丽媛 柴胡静脉乳剂的解热、镇痛作用.实用药物与临床2007年第10卷第5期270-272
[38] 安玉明,接传胤,祝世伟.柴胡的研究进展[J].人参研究,2001,13(1):11-13.
[39] 周玉皆,鲁珊,王志英等.葛根素对COPD大鼠气道炎症及气道重塑作用的研究.医学临床研究 2007年8月第24卷第8期:1249-1251
[40] 江苏医学院 中药大辞典 上海:上海科学技术出版社,1999:1077
[41] 国家中医药管理局。中华本草(下),上海:上海科学技术出版社,1998:2159
[42] Decker J et al. C.A. 1983; 99: 104z81C
[43] Tsitsa TzardiE et al. C. A1991; 114: 139650C
[44] Ji-nian Fang et al.phytochemistry 1990; 29 (9): 3019
[45] 张国升,凡明月,张佳美,方方,蔡艳丽等.芦根多糖的研究.中国医药学报.2002,17(4):250
[46] Janine E. Polifka,J.M. Friedman. Medical genetics: 1. Clinical teratology in the age of genomics. Canadian Medical Association or its licensors, 2002, 167:265-273.
[47] 吕伯钦等译 实验毒理学基础.北京人民卫生出版社,1987,1
[1] 唐贵忠 我国人口出生缺陷状况及干预措施的分析[J] 中华妇幼保健,2001,16(7):408-409
[2] 李希新,张恒齐、论妊娠禁忌药在妊娠期的应用、山东中医杂志,1999,18(8):368
[3] 张颂,张宗禹,石其贤,等、阿魏的终止妊娠作用、中草药,1991,22(10):458-459
[4] 柳红芳,高学敏、蒲黄水煎液对小鼠妊娠影响的实验研究、中药药理与临床,1994,10(2):26-29
[5] 国家中医药管理局《中华本草》编委会、中华本草(第一册)、上海:上海科学技术出版社,1995、235
[6] 宋树立、川牛膝水煎液影响小鼠妊娠的实验研究、中国医药学报,1994, 9(4):40
[7] 李仪奎,姜名瑛、中药药理学、北京:中国中医药出版社,1992、86
[8] 郭胜民,车锡平,范晓雯、怀牛肤皂苷A对离体大鼠子宫兴奋作用机理的研究、西安医科大学学报,1997,18(4):473
[9] 王世祥,车锡平、怀牛肤总皂苷对离体大鼠子宫的兴奋作用及机理研究、西北药学杂志,1996,11(4);160
[10] 朱和、牛肤总皂甙对动物子宫平滑肌的作用、中草药,1987,18(4):17
[11] 马永明,刘恒,瞿颂义,等、芫花对未孕大鼠离体子宫平滑肌条作用的研究、中国中药杂志,1998,23(4):429
[12] 吕富华,吴熙瑞,洪山海,等、益母草的药理研究(对子宫作用的第1次报告)、中华医学杂志,1954:40(9):699
[13] 潘思源,常英,魏路雪,等、茺蔚子总碱和水苏碱收缩离体小鼠子宫的比较、中草药,1998,29(10):687
[14] 何功倍,张世芳,王怀真,等、重楼排草对家兔、豚鼠、大鼠、小鼠 子中的作用、中成药研究,1986,(10):28
[15] 雎大簋,吕忠智,李淑惠、九里香化学及抗生育作用研究概况、中草药,1994.25(8):436
[16] 广西祟左县人民医院、中草药贯众注射液对子宫收缩临床应用的初步观察、中草药通讯,1970,(5):35
[17] 陈琦、贯众抗生育有效部分的药理研究、天津医药,1980,(8):488
[18] 高南南,于澍仁,冯毓秀,等、泽兰两个品种对小鼠离体子宫平滑肌的作用、基层中药杂志,1995,9(3):34
[19] 李卫民,高英,吕振兰,等、中草药抗生育研究、中国医药科技出版社,1993、342
[20] 周铭东,江燕,赵翠兰,等、扶桑花中石油醚溶物的组分研究及抗生育初探、云南中药杂志,1997,18(2):33
[21] 江燕,赵翠兰,李开源,等、扶桑花石油醚溶物(HR-1)对小鼠离体子宫兴奋作用的机理研究.云南中医中药杂志,1998,19(1):25
[22] 姜枫勤,刘世明,李克勤,等、逐瘀清官冲剂药效学研究山东中医药大学学报,1997,21(3):218
[23] 马永明,刘恒,瞿颂义,等、乌梅对大鼠离体子宫平滑肌条运动的影响及其机理探讨、中国中西医结合杂志,1998,(6):18
[24] 杨东焱,马永明,田治峰,等、乌梅对未孕和早孕大鼠子宫平滑肌电活动的影响及其机理探讨、成药,2000,22(12):850
[25] 闫升,乔国芳,刘志峰,等、当归油对大鼠离体子宫平滑肌收缩功能的影响、中草药,2000,31(8):606
[26] 李卫民,高英,吕振兰.等、中草药抗生育研究、北京:中国医药科技出版社,1993、342
[27] 吴克让、续断的药理作用、浙江中医学院学报,1983,7(增刊):2
[28] 龚小健,吴知行,陈真,等、川续断DA303对大鼠子宫的作用、中国药科大学学报,1996,27(1):48
[29] 吴佩君,陈活彝,吴子斌,等、天花粉蛋白对小鼠胚早期发育的影响、 生殖与避孕,1994,14(1):8-12
[30] 肖庆慈,毛小平.赵霞,等、妊娠禁忌药-斑蝥的部分药理研究、云南中医学院学报,2000,23(1):10
[31] 国家中医药管理局编委会、中华本草(第九册)、上海:上海科学技术出版社,1999、27-28
[32] 雷载权,张廷模、中华临床中药学、北京:人民卫生出版社、1988、141
[33] 秦伯未,张赞臣,徐福民,等、妊娠禁忌药的初频囊理、上海中医药杂志,1956;二月号:27-36
[34] 田新村、浅探中药妊娠禁忌、新疆中医药,1989,(4):44
[35] 国家中医药管理局编委会、中华本草(第一册)、上海:上海科学技术出版社,1999、249
[36] 郁加凡,楼星湟、妊娠期用药的临床体会、浙江中医学院学报,1982;(3): 24
[37] 杜惠兰,妊娠期中西药物用药禁忌.人民卫生出版社 2007,8: 25.
[38] 何绍奇、关于半夏用于妊娠恶阻的问题、广西中医药,1983:6(3):34
[39] 郭胜民,车锡平,范晓雯、怀牛膝皂甙A的抗生育作用和对离体子宫平滑肌的作用、西北药学杂志,1996,11(增刊)。46-49
[40] 朱和,车锡平、牛膝总皂苷对大鼠离体子宫兴奋作用机理的研究、中国药理学通报,1988,4(4):241
[41] 王本祥、现代中药药理学、天津:天津科学技术出版社,1997、905-906, 898-899,857-858,736-739,1263-1264
[42] 柳红芳,高学敏、蒲黄水煎液对小鼠妊娠影响的实验研究、中药药理与临床、1994,10(2):26-29
[43] 杨守业,何民,王岚,等、大黄对大白鼠妊娠和胚胎毒性研究、中国中西医结合杂志,1992,12(8):485
[44] 郑显理,罗连城,许树朴,等,妊娠期急性胰腺炎.天津医药杂志, 1966,(4):260
[45] 肖泓,肖庆慈,毛小平,等、地龙对妊娠影响之初探、云南中医学院虫类妊娠禁忌药的部分药理研究组,2000,(1):17-21
[46] 肖庆慈,毛小平,赵霞,等、妊娠禁用药-斑蝥的部分药理研究、云南中医学院虫类妊娠禁忌药的部分药理研究组,2000,(1):22-26
[47] 郭峰,李川生,周维登、天花粉对实验性肝癌腹水型的疗效观察及免疫机理的初步探讨、第二军医大学学报,1980,1(2):9-11
[48] 郭峰,李川生,刘潜心、天花粉抗实验性肝癌腹水免疫细胞变化观察、肿瘤,1986,6(6):274
[49] 郭峰,刘小平,徐瑛、天花粉对小鼠艾氏腹水癌的疗效和对红细胞周期的影响、中国中西医结合杂志,1998,18(1),35-37
[50] 毕黎琦,李洪军,张玉华、天花粉蛋白对黑色素瘤细胞凋亡及细胞周期的影响、中国中西医结合杂志,1998,18(1):35-37
[51] 包素珍,孙在典,张爱琴、中药蛇六谷对荷瘤小鼠S180抑瘤及细胞周期的影响、浙江中西医结合杂志,1999,9(3):162-163
[52] 包素珍,孙在典,张爱琴、蛇六谷诱导肿瘤细胞凋亡的实验研究、浙江中医杂志,1999,34(6):276
[53] 陈培丰,刘鲁明、中药蛇六谷抗癌活性及诱导癌细胞凋亡、中国中医基础学杂志,2000,6(9):30-32
[54] 陈国强、氧化砷诱导早幼粒细胞白血病细胞凋亡及其分子机制的初步研究、中华血液病杂志,1997,18(1):25
[55] 金恩波,姜名瑛,黄启福,等、中药十八反的药理研究、中成药研究,1982, (2):28
[56] 杨致礼,王佑之,吴成林,等、中药“十八反”在小白鼠上的毒性试验、甘肃农大学报,1982,(1):46
[57] 萧庆慈、中药十九畏的研究总结、云南中医学院学报,1998,21(增刊):1-3
[59] 凌一揆、中药学、上海:上海科学技术出版社、1984,12