活血消异方对子宫内膜异位症大鼠生育力和早期妊娠毒性的影响
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摘要
目的评价活血消异方对子宫内膜异位症(EMs)模型大鼠生育力、早期妊娠毒性的影响。方法采用改良同种异体移植法建立大鼠EMs模型,造模大鼠随机分为模型组和活血消异方低、高剂量(18、36 g/kg)组,行假手术操作的大鼠为假手术组,未经过任何处理的大鼠为空白组。每天ig给药1次,给药体积1 mL/100 g,连续给药至处死,空白组、假手术组、模型组同时ig等体积蒸馏水。给药3周后,将各组雌鼠分别与平行喂养的雄鼠以2∶1合笼交配,试验期间每天观察大鼠的活动、行为、步态和对外界的反应情况,记录死亡情况。孕6 d各组随机选取17只大鼠处死,计算妊娠率;未孕大鼠进行子宫硫化铵染色,确定是否有早期胚胎死亡。孕14 d各组随机选取8只大鼠,脱颈处死,常规消毒后开腹,取出双侧子宫、卵巢观察形态;纵行剖开子宫,记录着床数及活胎数、死胎数、吸收胎数,计算活胎率、着床前丢失率、着床后丢失率;并在显微镜下观察黄体数。结果试验期间各组大鼠的活动、行为、步态和对外界的反应情况正常,各组间大鼠体质量差异无统计学意义;在规定合笼时间内,各组妊娠率无明显差异,各组大鼠均未出现早期胚胎死亡情况;模型组着床数、活胎数明显少于空白组、假手术组,活血消异方低、高剂量组着床数、活胎数明显多于模型组,差异均有统计学意义(P<0.05);模型组着床前丢失率明显高于空白组、假手术组,活血消异方低、高剂量组着床前丢失率明显低于模型组,差异均有统计学意义(P<0.05)。活血消异方高、低剂量组黄体数、活胎数、着床数、死胎数、吸收胎数、活胎率、着床前丢失率、着床后丢失率与空白组比较无明显差异。结论 EMs疾病本身可降低大鼠生育力,但不存在早期胚胎毒性;活血消异方可在一定程度上提高EMs大鼠生育力,且不存在早期胚胎毒性。
Objective To evaluate the effect of Huoxue Xiaoyi Prescription on the early pregnancy toxicity of rats with endometriosis. Methods The endometriosis model rats were established by modified allograft method. The model rats were randomly divided into model group, Huoxue Xiaoyi Prescription low and high dose groups(18, 36 g/kg). The sham-operated rats were the sham-operated group, and the untreated rats were the blank group. The corresponding drugs were ig administered once daily with volume of 1 mL/100 g. The rats were administered to death continuously. The blank group, sham operation group and model group were administered distilled water at the same time. After 3 weeks of administration, female rats in each group were mated with parallel-fed male rats in a cage with rate of 2:1. Activity, behavior, gait and reaction to the outside world were observed daily during the experiment, and death was recorded. Seventeen rats in each group were killed at random on the 6 th day of gestation to calculate the pregnancy rate. Unpregnant rats were stained with ammonium sulfide to determine whether there was early embryo death. Eight rats in each group were randomly selected on the 14 th day of pregnancy and executed without cervix. After routine disinfection, the uterus and ovaries were opened to observe the morphology. The uterus was longitudinally dissected to record the number of live births, dead births, absorbed births, calculate the rate of live births, the rate of loss before and after implantation, and observe the number of corpus luteum under the microscope. Results During the experiment, the activity, behavior, gait and reaction to the outside world of rats in each group were normal, and there was no significant difference in body mass among groups; there was no significant difference in pregnancy rate among groups within the prescribed closure time, and no early embryo death occurred in each group; the number of implantation and live fetus in model group was significantly less than that in blank group and sham-operated group, and the number of implantation and live births in the Huoxue Xiaoyi Prescription of low and high dose group were significantly more than those in the model group(P < 0.05), the loss rate before implantation in the model group was significantly higher than that in the blank group and the sham operation group, and the loss rate before implantation in the low and high dose groups of Huoxue Xiaoyi Prescription was significantly lower than that in the model group(P < 0.05). The number of corpus luteum, live fetus, implantation number, stillbirth number, absorbed fetus number, live fetus rate, pre-implantation loss rate and post-implantation loss rate of Huoxue Xiaoyi Prescription group were not significantly different from those of blank group.Conclusion EMs can reduce the fertility of rats, but have no toxicity on the early embryo development of rats; Huoxue Xiaoyi Prescription can improve the fertility of EMs rats to a certain extent, and there is no toxicity to early embryos development of rats.
Objective To evaluate the effect of Huoxue Xiaoyi Prescription on the early pregnancy toxicity of rats with endometriosis. Methods The endometriosis model rats were established by modified allograft method. The model rats were randomly divided into model group, Huoxue Xiaoyi Prescription low and high dose groups(18, 36 g/kg). The sham-operated rats were the sham-operated group, and the untreated rats were the blank group. The corresponding drugs were ig administered once daily with volume of 1 mL/100 g. The rats were administered to death continuously. The blank group, sham operation group and model group were administered distilled water at the same time. After 3 weeks of administration, female rats in each group were mated with parallel-fed male rats in a cage with rate of 2:1. Activity, behavior, gait and reaction to the outside world were observed daily during the experiment, and death was recorded. Seventeen rats in each group were killed at random on the 6 th day of gestation to calculate the pregnancy rate. Unpregnant rats were stained with ammonium sulfide to determine whether there was early embryo death. Eight rats in each group were randomly selected on the 14 th day of pregnancy and executed without cervix. After routine disinfection, the uterus and ovaries were opened to observe the morphology. The uterus was longitudinally dissected to record the number of live births, dead births, absorbed births, calculate the rate of live births, the rate of loss before and after implantation, and observe the number of corpus luteum under the microscope. Results During the experiment, the activity, behavior, gait and reaction to the outside world of rats in each group were normal, and there was no significant difference in body mass among groups; there was no significant difference in pregnancy rate among groups within the prescribed closure time, and no early embryo death occurred in each group; the number of implantation and live fetus in model group was significantly less than that in blank group and sham-operated group, and the number of implantation and live births in the Huoxue Xiaoyi Prescription of low and high dose group were significantly more than those in the model group(P < 0.05), the loss rate before implantation in the model group was significantly higher than that in the blank group and the sham operation group, and the loss rate before implantation in the low and high dose groups of Huoxue Xiaoyi Prescription was significantly lower than that in the model group(P < 0.05). The number of corpus luteum, live fetus, implantation number, stillbirth number, absorbed fetus number, live fetus rate, pre-implantation loss rate and post-implantation loss rate of Huoxue Xiaoyi Prescription group were not significantly different from those of blank group.Conclusion EMs can reduce the fertility of rats, but have no toxicity on the early embryo development of rats; Huoxue Xiaoyi Prescription can improve the fertility of EMs rats to a certain extent, and there is no toxicity to early embryos development of rats.
引文
[1]孙伟伟,赵瑞华,李晶秋,等.中医辨证治疗子宫内膜异位症临床观察[J].中国中医药信息杂志, 2009, 16(6):70-71.
[2] Zhao Ruihua, Liu Yong, Tan Yong, et al. Chinese medicine improves postoperative quality of life in endometriosis patients:A randomized controlled trial[J].Chin J Integr Med, 2013, 19(1):15-21.
[3]张娟,赵瑞华.中药治疗子宫内膜异位症相关不孕症的临床研究[J].北京中医药, 2013, 32(11):855-857.
[4] ZHAO Ruihua, HAO Zengping, ZHANG Yi, et al.Controlling the recurrence of pelvic endometriosis after a conservative operation:Comparison between Chinese herbal medicine and western medicine[J]. Chin J Integr Med, 2013, 19(11):820-825.
[5]张薇,邹移海,胡海勋,等.同种异体移植子宫内膜异位症大鼠模型的建立[J].热带医学杂志, 2010, 10(7):770-772.
[6]李勇,张天宝.发育毒理学研究方法和实验技术[M].北京:北京医科大学出版社, 2000.
[7]赵瑞华,杨艳环,李敏,等.活血消异方对子宫内膜异位症大鼠ICAM-1、MMP-9及VEGF的影响[J].北京中医药大学学报, 2012, 35(12):826-829, 872.
[8]孙伟伟,杨艳环,郝增平,等.丹赤饮对子宫内膜异位症患者血清白细胞介素的影响[J].中国中医药信息杂志,2014, 21(6):14-17.
[9]吴天思,崔阳阳,孙伟伟,等.活血消异方对子宫内膜异位症模型小鼠子宫内膜容受性的影响研究[J].河北医药, 2017, 39(7):965-967, 972.
[10]杨艳环,赵瑞华,吴天思,等.活血消异方对子宫内膜异位症妊娠功能低下模型小鼠HOXA10基因的影响[J].辽宁中医杂志, 2016, 43(12):2639-2642.
[11]崔阳阳,孙伟伟,赵瑞华.子宫内膜异位症模型小鼠胞饮突时间位点观察[J].辽宁中医杂志, 2015, 42(1):200-202.
[12]杨艳环,赵瑞华,徐彩.活血消异方对子宫内膜异位症复发风险大鼠模型的影响[J].中华中医药杂志,2012, 27(7):1911-1913.
[2] Zhao Ruihua, Liu Yong, Tan Yong, et al. Chinese medicine improves postoperative quality of life in endometriosis patients:A randomized controlled trial[J].Chin J Integr Med, 2013, 19(1):15-21.
[3]张娟,赵瑞华.中药治疗子宫内膜异位症相关不孕症的临床研究[J].北京中医药, 2013, 32(11):855-857.
[4] ZHAO Ruihua, HAO Zengping, ZHANG Yi, et al.Controlling the recurrence of pelvic endometriosis after a conservative operation:Comparison between Chinese herbal medicine and western medicine[J]. Chin J Integr Med, 2013, 19(11):820-825.
[5]张薇,邹移海,胡海勋,等.同种异体移植子宫内膜异位症大鼠模型的建立[J].热带医学杂志, 2010, 10(7):770-772.
[6]李勇,张天宝.发育毒理学研究方法和实验技术[M].北京:北京医科大学出版社, 2000.
[7]赵瑞华,杨艳环,李敏,等.活血消异方对子宫内膜异位症大鼠ICAM-1、MMP-9及VEGF的影响[J].北京中医药大学学报, 2012, 35(12):826-829, 872.
[8]孙伟伟,杨艳环,郝增平,等.丹赤饮对子宫内膜异位症患者血清白细胞介素的影响[J].中国中医药信息杂志,2014, 21(6):14-17.
[9]吴天思,崔阳阳,孙伟伟,等.活血消异方对子宫内膜异位症模型小鼠子宫内膜容受性的影响研究[J].河北医药, 2017, 39(7):965-967, 972.
[10]杨艳环,赵瑞华,吴天思,等.活血消异方对子宫内膜异位症妊娠功能低下模型小鼠HOXA10基因的影响[J].辽宁中医杂志, 2016, 43(12):2639-2642.
[11]崔阳阳,孙伟伟,赵瑞华.子宫内膜异位症模型小鼠胞饮突时间位点观察[J].辽宁中医杂志, 2015, 42(1):200-202.
[12]杨艳环,赵瑞华,徐彩.活血消异方对子宫内膜异位症复发风险大鼠模型的影响[J].中华中医药杂志,2012, 27(7):1911-1913.