补肾化瘀方对PCO模型大鼠卵巢颗粒细胞膜上INSR和IGFR基因表达的影响
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摘要
目的：通过建立大鼠多囊卵巢动物模型,利用中药补肾化瘀方对其进行干预,探讨补肾化瘀方对多囊卵巢大鼠卵巢颗粒细胞膜上INSR基因和IGFR基因表达的影响,为临床治疗多囊卵巢综合征提供实验依据。
方法：选用6周龄SPF级SD雌性大鼠,有规律的动情周期,79只,以1：5随机分为空白对照组和造模组(空白对照组13只,造模组66只),造模组用0.125mg/ml的来曲唑-羧甲基纤维素溶液,按照8ml/kg的剂量给实验大鼠灌胃,每天一次,共21天。空白对照组动物按8ml/kg的剂量给实验大鼠灌胃服用1%羧甲基纤维素水溶液,每天一次,共21天。造模成功后,将造模组随机分为五组,分别为组一(模型对照组)13只,组二(补肾化瘀方高剂量组)14只,组三(补肾化瘀方中剂量组)13只,组四(补肾化瘀方低剂量组)13只,组五(阳性药物对照组)13只。空白对照组为组六13只。将补肾化瘀方制成2.66g/ml的汤剂,补肾化瘀方低剂量组、补肾化瘀方中剂量组、补肾化瘀方高剂量组分别取8ml、15ml、30ml稀释为30ml、30ml、32ml,按1ml／150g灌服,(Qd×3d,休息1d),连续84天；阳性药物对照组每日将1片达英-35溶于64ml蒸馏水中,按1ml/150g灌服,(Qd×3d,休息1d),连续84天,模型对照组与空白对照组每天灌胃同体积生理盐水。各组大鼠于实验观察结束后处死取材。
结果：经统计处理,各组卵巢中卵泡的颗粒细胞膜上可检测到INSR基因和IGFR基因的表达,模型对照组卵泡的颗粒细胞中INSR基因与IGFR基因表达量均低于空白对照组、补肾化瘀方高剂量组、补肾化瘀方中剂量组、补肾化瘀方低剂量组及阳性药物对照组(P<0.05)；空白对照组、补肾化瘀方高剂量组、补肾化瘀方中剂量组、补肾化瘀方低剂量组及阳性药物对照组五组间比较无统计学意义(P>0.05)。
结论：上述实验结果表明INSR基因与IGFR基因的表达异常可能是多囊卵巢的关健因素,中药补肾化瘀方通过调节INSR基因与IGFR基因的异常表达,从而发挥治疗多囊卵巢的作用。其疗效并不亚于临床常用的西药达英-35。
Objective:By establishing animal model of rat PCO, we used traditional Chinese medicine named Kidney Huayu Recipe to interfere the model, then to discuss the effect of Kidney Huayu Recipe on the expression of INSR gene and IGFR gene in PCO model rat ovarian granulose cell membrane.We wished all this could provide the experiment evidence for clinical therapy of PCOS.
Methods:69 cases of female SD rat at 6-week,becoming enamoured having a law periods,were at random divided into six groups, including Group One (model control group) 13 cases,Group Two(high dosages of traditional Chinese medicine group) 14cases,Group Three(middle dosages of traditional Chinese medicine group) 13 cases, Group Four(low dosages of traditional Chinese medicine group) 13 cases, Group Five(Positive Drug control group) 13 cases, Group Six(blank space control group) 13 cases.Group one, two, three, four and five were fed with 0.125 mg/ml Letrozole-Carboxyl methyl cellulose solution,8ml/kg per cases, once a day, last 21 days. Group six according to 8ml/kg per cases were fed with 1% carboxyl methyl cellulose solution,once a day,last 21 days. Afterwar- ds, decocted Kidney Huayu Recipe with water made 2.66 g/ml, low dosages of traditional Chinese medicine group,middle dosages of traditional Chinese medicine group and high dosages of traditional Chinese medicine group were taken 8ml,15ml,30ml diluted to 30ml, 30ml,32ml, fed with lml/150g per cases, (Qd×3 ds, rest 1 d),last 84 days; Positive Drug control group were fed with UK-35,of which were dissolved 1 piece in 64ml distilled water everyday, according to 150ml/g,(Qd×3 ds,rest 1 d),last 84 days, model control group and the blank space control group irrigates were fed with the same volume physiological saline every day. After the end of experimental observation, rats in each group were put to death and drawn.
Results:After statistical processing, all of the groups can be detected INSR gene and IGFR gene expressing in the ovarian granulosa cell membrane, in the model control group,INSR gene and IGFR gene expression in significantly lower than blank control group, high dosages of traditional Chinese medicine group, middle dosages of traditional Chinese medicine group,low dosages of traditional Chinese medicine group and Positive Drug control group(P<0.05);blank control group, high dosages of traditional Chinese medicine group,middle dosages of traditional Chinese medicine group,low dosages of traditional Chinese medicine group and Positive Drug control group have no statistically significance among the five set of groups.(P>0.05).
Conclusion:These experimental results show that abnormal expression of INSR gene and IGFR gene may be a crucial factor in women with polycystic ovary, by regulating the abnormal expression of INSR gene and IGFR gene,Chinese medicine:Kidney Huayu Recipe play an important role in the treatment of polycystic ovary. Its clinical efficacy is no less than the western medicine commonly used in clinic:Diane-35.
方法：选用6周龄SPF级SD雌性大鼠,有规律的动情周期,79只,以1：5随机分为空白对照组和造模组(空白对照组13只,造模组66只),造模组用0.125mg/ml的来曲唑-羧甲基纤维素溶液,按照8ml/kg的剂量给实验大鼠灌胃,每天一次,共21天。空白对照组动物按8ml/kg的剂量给实验大鼠灌胃服用1%羧甲基纤维素水溶液,每天一次,共21天。造模成功后,将造模组随机分为五组,分别为组一(模型对照组)13只,组二(补肾化瘀方高剂量组)14只,组三(补肾化瘀方中剂量组)13只,组四(补肾化瘀方低剂量组)13只,组五(阳性药物对照组)13只。空白对照组为组六13只。将补肾化瘀方制成2.66g/ml的汤剂,补肾化瘀方低剂量组、补肾化瘀方中剂量组、补肾化瘀方高剂量组分别取8ml、15ml、30ml稀释为30ml、30ml、32ml,按1ml／150g灌服,(Qd×3d,休息1d),连续84天；阳性药物对照组每日将1片达英-35溶于64ml蒸馏水中,按1ml/150g灌服,(Qd×3d,休息1d),连续84天,模型对照组与空白对照组每天灌胃同体积生理盐水。各组大鼠于实验观察结束后处死取材。
结果：经统计处理,各组卵巢中卵泡的颗粒细胞膜上可检测到INSR基因和IGFR基因的表达,模型对照组卵泡的颗粒细胞中INSR基因与IGFR基因表达量均低于空白对照组、补肾化瘀方高剂量组、补肾化瘀方中剂量组、补肾化瘀方低剂量组及阳性药物对照组(P<0.05)；空白对照组、补肾化瘀方高剂量组、补肾化瘀方中剂量组、补肾化瘀方低剂量组及阳性药物对照组五组间比较无统计学意义(P>0.05)。
结论：上述实验结果表明INSR基因与IGFR基因的表达异常可能是多囊卵巢的关健因素,中药补肾化瘀方通过调节INSR基因与IGFR基因的异常表达,从而发挥治疗多囊卵巢的作用。其疗效并不亚于临床常用的西药达英-35。
Objective:By establishing animal model of rat PCO, we used traditional Chinese medicine named Kidney Huayu Recipe to interfere the model, then to discuss the effect of Kidney Huayu Recipe on the expression of INSR gene and IGFR gene in PCO model rat ovarian granulose cell membrane.We wished all this could provide the experiment evidence for clinical therapy of PCOS.
Methods:69 cases of female SD rat at 6-week,becoming enamoured having a law periods,were at random divided into six groups, including Group One (model control group) 13 cases,Group Two(high dosages of traditional Chinese medicine group) 14cases,Group Three(middle dosages of traditional Chinese medicine group) 13 cases, Group Four(low dosages of traditional Chinese medicine group) 13 cases, Group Five(Positive Drug control group) 13 cases, Group Six(blank space control group) 13 cases.Group one, two, three, four and five were fed with 0.125 mg/ml Letrozole-Carboxyl methyl cellulose solution,8ml/kg per cases, once a day, last 21 days. Group six according to 8ml/kg per cases were fed with 1% carboxyl methyl cellulose solution,once a day,last 21 days. Afterwar- ds, decocted Kidney Huayu Recipe with water made 2.66 g/ml, low dosages of traditional Chinese medicine group,middle dosages of traditional Chinese medicine group and high dosages of traditional Chinese medicine group were taken 8ml,15ml,30ml diluted to 30ml, 30ml,32ml, fed with lml/150g per cases, (Qd×3 ds, rest 1 d),last 84 days; Positive Drug control group were fed with UK-35,of which were dissolved 1 piece in 64ml distilled water everyday, according to 150ml/g,(Qd×3 ds,rest 1 d),last 84 days, model control group and the blank space control group irrigates were fed with the same volume physiological saline every day. After the end of experimental observation, rats in each group were put to death and drawn.
Results:After statistical processing, all of the groups can be detected INSR gene and IGFR gene expressing in the ovarian granulosa cell membrane, in the model control group,INSR gene and IGFR gene expression in significantly lower than blank control group, high dosages of traditional Chinese medicine group, middle dosages of traditional Chinese medicine group,low dosages of traditional Chinese medicine group and Positive Drug control group(P<0.05);blank control group, high dosages of traditional Chinese medicine group,middle dosages of traditional Chinese medicine group,low dosages of traditional Chinese medicine group and Positive Drug control group have no statistically significance among the five set of groups.(P>0.05).
Conclusion:These experimental results show that abnormal expression of INSR gene and IGFR gene may be a crucial factor in women with polycystic ovary, by regulating the abnormal expression of INSR gene and IGFR gene,Chinese medicine:Kidney Huayu Recipe play an important role in the treatment of polycystic ovary. Its clinical efficacy is no less than the western medicine commonly used in clinic:Diane-35.
引文
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[1]李美芝.多囊卵巢综合征的诊断与治疗.中华妇产科杂志,2002；37(7)：444.
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[4]许昕.对42例排卵障碍的妇女的辨证论治与高血睾现象分析[J].北京中医,1996,(5)：21.
[5]赵虹.黄芪丹参为主中药治疗高雄激素血症的临床研究.现代中西医结合杂志,2005；14(4)：466.
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[7]冯光荣,周艳艳,胡晓华.补肾调经汤对PCO大鼠血清性激素及卵巢形态学影响的实验研究术.中医研究.2009,3(22)：18-22.
[8]王砚琳.补肾活血化痰方治疗多囊卵巢综合征所致不孕的临床观察.中医药学刊.2005,23(8)：1519-1520.
[9]章巧萍,浅谈补肾活血法治疗多囊卵巢综合征.中国中医药信息杂志,2004,11(11)：1014.
[10]王针织,俞超芹.补肾活血化痰法治疗多囊卵巢综合征的临床观察.实用中西医结合临床.2010,1(10)：1-3.
[11]李喜莲,王针织,俞超芹.补肾活血化瘀方上调雄激素致不孕大鼠脂肪组织中胰岛素受体底物1及其酪氨酸磷酰化.中西医结合学报.2008,6(6)：621-625.
[12]申霞.补肾活血方治疗多囊卵巢综合征105例.世界中西医结合杂志.2006,1(2)：123-124.
[13]江胜芳,王华,黄晓卉,张昌军.补肾活血汤对多囊卵巢大鼠卵巢形态及颗粒细胞凋亡的影响.中国医院药学杂志2008,28(21)：1835-1836.
[2]Vink J.Heritability of polycystic ovary syndrome in a Dutch twin-family study.J Clin Endocrinol Metab,2005,91(6):2100-2104.
[3]Dunaif A,Thomas A.Current concepts in the polycystic ovary syndrome[J].Annu Bev Med,2001,52(1):401-419.
[4]崔乐英.达英—35二甲方双胍治疗多囊卵巢综合征[J].医药论坛杂志,2007,28(20)：34-35.
[5]胡颜,张展,贾莉婷.来曲唑诱导多囊卵巢综合征大鼠模型的研究.中国妇幼保健.2006,21(7)：957-959.
[6]徐叔云,卞如濂,陈修,等.药理实验方法学[M].第三版.北京：人民卫生出社.2006：1861.
[7]陈主初,吴端生.实验动物学[M].第一版.长沙：湖南科学技术出版社.2006：183.
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