孕康口服液对肾虚-黄体抑制型先兆流产大鼠的安胎作用
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摘要
目的:孕康口服液为已上市中成药,为进一步评价其药效,本实验通过建立肾虚-黄体抑制型先兆流产模型,观察孕康口服液的安胎作用。方法:60只妊娠大鼠随机分为正常对照组(NC),模型组(MG),地屈孕酮组(DT,3.02 mg/kg),孕康口服液低剂量组(YK-L,4 ml/kg)、中剂量组(YK-M,6 ml/kg)、高剂量组(YK-H,9 ml/kg),每组10只。自妊娠第1日,每日上午各给药组按规定剂量灌予受试药,NC组、MG组给予等体积的纯化水,连续10d;每天下午灌胃造模,除NC组给予纯化水外,其余各组按450 mg/kg体质量灌胃羟基脲,连续9 d,第10日按4.0mg/kg体质量灌胃米非司酮。妊娠第9日,测定各组大鼠背温、抓力、痛阈、自主活动等行为体征;妊娠第11日,各组腹主动脉取血,测定血清雌二醇(E2)、孕酮(P)、血栓素B2(TXB_2)水平;摘取卵巢、连胎子宫,观察胚胎个数和直径,计算卵巢、连胎子宫指数。结果:与NC组比较,MG组背温、抓力、痛阈、自主活动次数、胚胎个数、胚胎直径、连胎子宫指数和血清E2、P、TXB_2水平均显著降低(P<0.05,0.01)。与MG组比较,孕康口服液各剂量组背温、抓力、胚胎个数、胚胎直径和血清E2、P水平均显著升高(P<0.05,0.01); YK-M、YK-H组痛阈、自主活动、连胎子宫指数显著升高(P<0.05); YK-H组血清TXB_2水平明显升高(P<0.05)。结论:孕康口服液对肾虚-黄体抑制导致的先兆流产大鼠具有明确的补肾安胎作用,其机制可能与升高血清E2、P、TXB_2水平,改善肾虚体征和提高胚胎质量有关。
Objective: Yun Kang oral liquid is a listed proprietary Chinese Medicine. To further evaluate its efficacy,this experiment established a kidney deficiency and luteum inhibition threatened abortion rat model to observe the effects of Yun Kang oral liquid.Methods: Sixty pregnant rats were randomly divided into normal control group( NC),model group( MG),dydrogesterone group( DT,3.02 mg/kg),and Yun Kang oral liquid low-dose group( YK-L,4 ml/kg),medium dose group( YK-M,6 ml/kg),high dose group( YK-H,9 ml/kg),10 in each group. On the first day of pregnancy,each administration group was treated with the test drug at the prescribed dose every morning,and the NC group and the MG group were given an equal volume of purified water for 10 days; the rats were intragastrically administrated every afternoon,except for the NC group. In addition,the other groups were intragastrically administered with hydroxyurea at a dose of 450 mg/kg for 9 days,and mifepristone was administered at a dose of 4.0 mg/kg on the 10 th day. On the 9 th day of pregnancy,behavioral signs such as back temperature,grasping force,pain threshold,and autonomic activity were measured in each group. On the 11 th day of pregnancy,blood was collected from the abdominal aorta in each group to determine serum levels of estradiol( E2),progesterone( P) and thromboxane B2( TXB_2). Ovary and fetal uterus were removed,the number and diameter of embryos were observed,and the ovary and uterus indexes were calculated. Results: Compared with the NC group,the back temperature,grip,pain threshold,number of spontaneous activities,number of embryos,embryo diameter,uterus index and serum E2,P,TXB_2 levels in the MG group were decreased significantly( P<0.05,0.01). Compared with the MG group,the back temperature,grasping force,number of embryos,embryo diameter and serum E2 and P levels were increased significantly in each dose group( P<0.05,0.01); the pain threshold,autonomic activity,and uterus index of YK-M and YK-H group were increased significantly( P<0.05); serum level of TXB_2 in YK-H group were increased significantly( P< 0.05). Conclusion: Yun Kang oral liquid has a clear kidney-filling effect on rats with threatened abortion caused by kidney deficiency-luteal suppression. The mechanism may be related to raising serum E2,P,TXB_2 levels,improving kidney deficiency and improving embryo quality.
Objective: Yun Kang oral liquid is a listed proprietary Chinese Medicine. To further evaluate its efficacy,this experiment established a kidney deficiency and luteum inhibition threatened abortion rat model to observe the effects of Yun Kang oral liquid.Methods: Sixty pregnant rats were randomly divided into normal control group( NC),model group( MG),dydrogesterone group( DT,3.02 mg/kg),and Yun Kang oral liquid low-dose group( YK-L,4 ml/kg),medium dose group( YK-M,6 ml/kg),high dose group( YK-H,9 ml/kg),10 in each group. On the first day of pregnancy,each administration group was treated with the test drug at the prescribed dose every morning,and the NC group and the MG group were given an equal volume of purified water for 10 days; the rats were intragastrically administrated every afternoon,except for the NC group. In addition,the other groups were intragastrically administered with hydroxyurea at a dose of 450 mg/kg for 9 days,and mifepristone was administered at a dose of 4.0 mg/kg on the 10 th day. On the 9 th day of pregnancy,behavioral signs such as back temperature,grasping force,pain threshold,and autonomic activity were measured in each group. On the 11 th day of pregnancy,blood was collected from the abdominal aorta in each group to determine serum levels of estradiol( E2),progesterone( P) and thromboxane B2( TXB_2). Ovary and fetal uterus were removed,the number and diameter of embryos were observed,and the ovary and uterus indexes were calculated. Results: Compared with the NC group,the back temperature,grip,pain threshold,number of spontaneous activities,number of embryos,embryo diameter,uterus index and serum E2,P,TXB_2 levels in the MG group were decreased significantly( P<0.05,0.01). Compared with the MG group,the back temperature,grasping force,number of embryos,embryo diameter and serum E2 and P levels were increased significantly in each dose group( P<0.05,0.01); the pain threshold,autonomic activity,and uterus index of YK-M and YK-H group were increased significantly( P<0.05); serum level of TXB_2 in YK-H group were increased significantly( P< 0.05). Conclusion: Yun Kang oral liquid has a clear kidney-filling effect on rats with threatened abortion caused by kidney deficiency-luteal suppression. The mechanism may be related to raising serum E2,P,TXB_2 levels,improving kidney deficiency and improving embryo quality.
引文
[1]孙晶.血清孕酮、β-HCG联合检测在早期先兆流产中的诊断价值[J].中国生化药物杂志,2015,35(4):94-96.
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[5]郜洁,巫海旺,杜鑫,等.正交设计法研究羟基脲和米非司酮的优选配比制作大鼠流产模型[J].中国实验方剂学杂志,2016,22(16):114-118.
[6]吴春平,王国红,张勇,等.米非司酮对孕酮防护PC12细胞氧糖剥夺损伤的影响[J].中国应用生理学杂志,2013,29(2):132-134.
[7]邓欣.地屈孕酮与黄体酮治疗先兆流产的临床疗效比较研究[J].临床合理用药杂志,2017,10(18):65-66.
[8]赵薇,程丹玲,郑慧丽,等.PACAP mRNA在大鼠妊娠黄体及离体细胞的表达与调节[J].中国应用生理学杂志,2010,26(3):313-317.
[9]王丽君,胡晨,吴江平.黄体功能不全先兆流产的治疗及血清孕酮值与治疗结局的相关性分析[J].现代妇产科进展,2015(1):40-43.
[10]贺娟.血清E2、P、β-HCG与妊娠早期孕妇先兆流产的相关性分析[J].中国优生与遗传杂志,2016(7):55-57.
[11]郜洁,罗颂平.寿胎丸对肾虚-黄体抑制流产模型大鼠雌激素水平的影响[J].现代药物与临床,2011,26(4):287-289.
[2]Reis MF,Aniceto P,Aguiar P,et al.Quantification of urinary chorionic gonadotropin in spontaneous abortion of pre-clinically recognized pregnancy:method development and analytical validation[J].Int J Hyg Environ Health,2007,210(3-4):419-427.
[3]梁欣韫.中医药治疗先兆流产研究进展[J].中医学报,2012,27(12):1663-1665.
[4]孟鸿雁,卢路艳,马永莉,等.马春芬教授治疗先兆流产经验拾要[J].中医研究,2011,24(3):62-63.
[5]郜洁,巫海旺,杜鑫,等.正交设计法研究羟基脲和米非司酮的优选配比制作大鼠流产模型[J].中国实验方剂学杂志,2016,22(16):114-118.
[6]吴春平,王国红,张勇,等.米非司酮对孕酮防护PC12细胞氧糖剥夺损伤的影响[J].中国应用生理学杂志,2013,29(2):132-134.
[7]邓欣.地屈孕酮与黄体酮治疗先兆流产的临床疗效比较研究[J].临床合理用药杂志,2017,10(18):65-66.
[8]赵薇,程丹玲,郑慧丽,等.PACAP mRNA在大鼠妊娠黄体及离体细胞的表达与调节[J].中国应用生理学杂志,2010,26(3):313-317.
[9]王丽君,胡晨,吴江平.黄体功能不全先兆流产的治疗及血清孕酮值与治疗结局的相关性分析[J].现代妇产科进展,2015(1):40-43.
[10]贺娟.血清E2、P、β-HCG与妊娠早期孕妇先兆流产的相关性分析[J].中国优生与遗传杂志,2016(7):55-57.
[11]郜洁,罗颂平.寿胎丸对肾虚-黄体抑制流产模型大鼠雌激素水平的影响[J].现代药物与临床,2011,26(4):287-289.