子宫内膜异位症动物模型中整合素β3的表达及中药干预作用的研究
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摘要
目的通过动物实验建立子宫内膜异位症大鼠模型,研究整合素β3在子宫内膜异位症大鼠模型中的表达情况,研究温经化瘀散结中药复方对整合素β3在子宫内膜异位症大鼠模型中的表达的干预作用,研究中药对子宫内膜异位症的防治作用,为中药制剂在治疗子宫内膜异位症方面的临床应用提供理论依据,促进中医药的推广应用。
方法以清洁级雌性成熟未交配过的SD大鼠(体重180-220g)为实验对象。进行子宫内膜异位症动物模型实验。造模方式采用自体移植法,开腹后将其自体子宫内膜分离后缝于腹壁上。将所有大鼠随机分为中药组、丹那唑组、造模对照组及空白对照组。中药组、丹那唑组及造模对照组分别各组17只大鼠进行造模。空白对照组14只大鼠进行假手术,开腹后将一侧子宫角结扎,目的使假手术组达到与造模模型组均为单侧宫角子宫的生殖环境。监测模型大鼠的情况及检测模型大鼠及对照组大鼠的整合素β3和血雌二醇、孕酮、Ca125。采用灌胃给药法：自体移植造模手术及假手术后一个月始四组分别给予中药液(温经化瘀散结中药复方)、丹那唑、生理盐水、生理盐水,每天一次,连续8周。第八周末处死各组大鼠,观察移植物生长情况及检测各项指标。结果以均数±标准差表示。用SPSS11.0软件进行统计分析。结果与空白对照组相比,造模对照组血孕酮下降,Ca125轻度升高,整合素β3表达下降(P<0.05)。种植灶组织形态学观察有子宫内膜腺体或上皮、间质细胞。丹那唑组与造模对照组相比Ca125降低明显,而血孕酮亦降低(P<0.05),整合素β3变化则无显著差异。而中药组Ca125较造模对照组亦有下降,与丹那唑组相比,血雌二醇、孕酮、整合素β3明显升高(P<0.05)。中药组雌二醇、孕酮、整合素β3与空白对照组相比无显著性差异,
结论1、整合素β3在子宫内膜异位症大鼠模型中的表达较正常大鼠下降。
2、温经化瘀散结中药复方能使子宫内膜异位症大鼠模型整合素β3表达升高,从而改善大鼠子宫内膜的容受性,使得妊娠机率提高。
OBJECTIVE:By establishing an experimental rat model of endometriosis, to examine the expression of Integrinβ3 in rat endometriosis, and to further investigate the regulation of traditional Chinese medicine on the expression of Integrinβ3 in the rat model. To show the efficacy of Chinese medicine for treating endometriosis in an experimental model, which may be served as theoretical basis for clinical application of Chinese medicine in endometriosis therapy.
METHODS:51 female virgin SD rats (weight 180g-220g), in which endometrial implants were induced by transplanting autologous endometrium pieces to the peritoneum, were randomly divided into three groups equally: (1) the traditional Chinese medicine group; (2) the Danazol group; and (3) the model group (saline solution). Another 14 rats were treated as the sham surgery group. One month after surgery, rats were intragastrically administered once a day. Eight weeks later, we examined the pathological alteration of implants, the expression of Integrinβ3, and the serum levels of Estradiol, Progesterone and Ca125 on each group. All the data are presented as means±sem. The statistical analysis was performed by using SPSS11.0 software.
RESULTS:Statistical analysis showed that compared to the sham surgery group, the serum level of Ca 125 in the model group was elevated, the level of progesterone was decreased, and the expression of integrinβ3 was significantly reduced (P<0.05). Compared to the model group, the serum Ca 125 level and the serum progesterone were significantly decreased (P<0.05), while there was no significant difference in the levels of and the integrinβ3 expression in the Danazol group. In the traditional Chinese medicine group, the serum Ca 125 level was reduced compared to the model group while the levels of serum estradiol, progesterone and the integrinβ3 expression were higher than those of the Danazol group (P<0.05).
CONCLUSIONS:1) the serum level of progesterone and the expression of integrinβ3 were reduced while the serum level of Ca 125 was elevated in the rat endometriosis model compared to the normal rats.2) traditional Chinese medicine and danazol have an effect to reduce the volume of lesion and to decrease the serum Ca125 level in the rat endometriosis model.3) While danazol failed to increase the expression of integrin 03, traditional Chinese medicine plays an important role in promoting the levels of the serum progesterone and the expression of integrinβ3, which can promote the endometrial receptivity and increase pregnancy ratio.
方法以清洁级雌性成熟未交配过的SD大鼠(体重180-220g)为实验对象。进行子宫内膜异位症动物模型实验。造模方式采用自体移植法,开腹后将其自体子宫内膜分离后缝于腹壁上。将所有大鼠随机分为中药组、丹那唑组、造模对照组及空白对照组。中药组、丹那唑组及造模对照组分别各组17只大鼠进行造模。空白对照组14只大鼠进行假手术,开腹后将一侧子宫角结扎,目的使假手术组达到与造模模型组均为单侧宫角子宫的生殖环境。监测模型大鼠的情况及检测模型大鼠及对照组大鼠的整合素β3和血雌二醇、孕酮、Ca125。采用灌胃给药法：自体移植造模手术及假手术后一个月始四组分别给予中药液(温经化瘀散结中药复方)、丹那唑、生理盐水、生理盐水,每天一次,连续8周。第八周末处死各组大鼠,观察移植物生长情况及检测各项指标。结果以均数±标准差表示。用SPSS11.0软件进行统计分析。结果与空白对照组相比,造模对照组血孕酮下降,Ca125轻度升高,整合素β3表达下降(P<0.05)。种植灶组织形态学观察有子宫内膜腺体或上皮、间质细胞。丹那唑组与造模对照组相比Ca125降低明显,而血孕酮亦降低(P<0.05),整合素β3变化则无显著差异。而中药组Ca125较造模对照组亦有下降,与丹那唑组相比,血雌二醇、孕酮、整合素β3明显升高(P<0.05)。中药组雌二醇、孕酮、整合素β3与空白对照组相比无显著性差异,
结论1、整合素β3在子宫内膜异位症大鼠模型中的表达较正常大鼠下降。
2、温经化瘀散结中药复方能使子宫内膜异位症大鼠模型整合素β3表达升高,从而改善大鼠子宫内膜的容受性,使得妊娠机率提高。
OBJECTIVE:By establishing an experimental rat model of endometriosis, to examine the expression of Integrinβ3 in rat endometriosis, and to further investigate the regulation of traditional Chinese medicine on the expression of Integrinβ3 in the rat model. To show the efficacy of Chinese medicine for treating endometriosis in an experimental model, which may be served as theoretical basis for clinical application of Chinese medicine in endometriosis therapy.
METHODS:51 female virgin SD rats (weight 180g-220g), in which endometrial implants were induced by transplanting autologous endometrium pieces to the peritoneum, were randomly divided into three groups equally: (1) the traditional Chinese medicine group; (2) the Danazol group; and (3) the model group (saline solution). Another 14 rats were treated as the sham surgery group. One month after surgery, rats were intragastrically administered once a day. Eight weeks later, we examined the pathological alteration of implants, the expression of Integrinβ3, and the serum levels of Estradiol, Progesterone and Ca125 on each group. All the data are presented as means±sem. The statistical analysis was performed by using SPSS11.0 software.
RESULTS:Statistical analysis showed that compared to the sham surgery group, the serum level of Ca 125 in the model group was elevated, the level of progesterone was decreased, and the expression of integrinβ3 was significantly reduced (P<0.05). Compared to the model group, the serum Ca 125 level and the serum progesterone were significantly decreased (P<0.05), while there was no significant difference in the levels of and the integrinβ3 expression in the Danazol group. In the traditional Chinese medicine group, the serum Ca 125 level was reduced compared to the model group while the levels of serum estradiol, progesterone and the integrinβ3 expression were higher than those of the Danazol group (P<0.05).
CONCLUSIONS:1) the serum level of progesterone and the expression of integrinβ3 were reduced while the serum level of Ca 125 was elevated in the rat endometriosis model compared to the normal rats.2) traditional Chinese medicine and danazol have an effect to reduce the volume of lesion and to decrease the serum Ca125 level in the rat endometriosis model.3) While danazol failed to increase the expression of integrin 03, traditional Chinese medicine plays an important role in promoting the levels of the serum progesterone and the expression of integrinβ3, which can promote the endometrial receptivity and increase pregnancy ratio.
引文
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