宫宁颗粒调控IUD出血副反应子宫内膜剥脱/修复相关机制的临床和实验研究
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摘要
目的:探讨宫宁颗粒调控宫内节育器(IUD)出血副反应子宫内膜剥脱/修复的相关机制。
     方法:临床试验中,对IUD出血副反应患者进行宫宁颗粒和消炎痛两种药物干预,并设未放置IUD月经正常的空白对照组,在观察疗效的同时,采用宫腔镜对子宫内膜的IUD压迫区、移行区和远器区进行观察并定点取材,比较各区治疗前后及与空白对照组在显微、超微结构方面的组织形态学变化,并检测ER(雌激素受体)、PR(孕激素受体)、VEGF(血管内皮生长因子)及其受体KDR、t-PA(组织型纤溶酶原激活剂)、PAI(纤溶酶原激活剂抑制剂)的表达情况;动物实验中,对大鼠子宫行IUD造模后,分为空白对照组、假手术组、模型组、宫宁大、中、小剂量组和消炎痛组,采用改良单宁酸-Fe法观察各组大鼠药物干预后子宫血管构筑的变化。
     结果:宫宁颗粒的临床疗效、中医证候改善率明显优于消炎痛组(P<0.05或P<0.01)。形态学观察表明,IUD出血副反应患者子宫内膜较之正常对照组,存在明显的显微、超微结构病理损伤和内膜发育不同步、剥脱/修复障碍的现象,且内膜损伤程度与距离IUD的远近成反比,距离越近,损伤越重;子宫内膜ER、PR、VEGF、KDR、t-PA、PAI的表达均与距离IUD远近成正比,距离越近,表达越低,较之正常对照组,VEGF、KDR、t-PA表达显著升高(P<0.05),PAI显著降低(P<0.05),且ER、VEGF、KDR、t-PA、PAI在内膜不同部位的表达均显著不同步(P<0.05或P<0.01)。IUD出血副反应患者治愈或好转后,较之治疗前,子宫内膜病理损害、发育不同步和剥脱/修复障碍的现象消失或明显减轻,VEGF、KDR、t-PA表达降低,PR、PAI表达升高,各指标在内膜不同部位变化幅度虽不一致(P<0.05或>0.05),但ER、VEGF、KDR、t-PA、PAI的表达不同步现象均消失(P>0.05);在减轻内膜病理损害和改善内膜各部分ER、VEGF、KDR、t-PA、PAI表达不同步方面,宫宁颗粒明显优于消炎痛(P<0.05)。动物实验表明,宫宁颗粒和消炎痛均能改善IUD模型大鼠子宫血构筑异常的改变,尤以宫宁大、中剂量组的改善作用显著。
     结论:瘀热型IUD出血副反应患者存在明显的子宫内膜剥脱/修复障碍,宫宁颗粒通过减轻内膜显微、超微结构的形态学损伤,调控内膜ER、PR、VEGF、KDR、t-PA、PAI表达,消除子宫血管构筑的异常,纠正了子宫内膜剥脱/修复障碍,从而达到防治IUD出血副反应的效果,且宫宁颗粒的临床疗效、中医证候疗效和对内膜剥脱/修复障碍相关指标的改善作用明显优于消炎痛。
Objective: To discuss the endometria’s peeling and recovery mechanism concerning control of the side reaction of bleeding after IUD placement by Gongning granula.
     Method: In the clinical experimental investigation , Gongning granula and Indometacin are used for the patients suffered by side reaction of bleeding,and it is assumed that without IUD blank group is placed;while observing herapeutic effect,uterine cavity is also adopted to observe pressure area,transition area and distant area,and sample is taken at a certain point. changes of different parts prior to and after the treatment are compared,those parts and the blank control groups are also compared in terms of conventional organization morphology and Ultrastructura,and the empress of ER、PR、VEGF、KDF、t-PA and PAI are examined;in animal test,after IUD placed in rat’s uterus,it is divided into blank group,sham operation group,model group,max-dosage group,mid-dosage group,min-dosage group and Indometacin group,and improved Tannin-Fe method is adopted to observe the changes of uterus angioarchitecture of rat in different groups after medicine effect.
     Results: the clinical curative effect and the improvement rate of traditional Chinese medicine of Gongning granula obviously better than Indometacin group(P<0.05).The observation of morphology indicate that,the endometria’s of the patients that the adverse reaction of bleeding after IUD placement exist obviously patho-damagement in histological anatomy and ultrastructural organization,it’s degree of the patho-damagement inverse proported with the distance to IUD,the farther distance the slighter pain, as well it appears the obviously derangement of endometria’s and the disturbance of stripping or recovery. Compare to normal control,the empress of the endometrias VEGF,KDR and t-PA obviously heigh(tP<0.05),the empress of the PAI obviously degrade,the empress of each indicatrix for the different location at endometria’s obviously discrepancy as well,the empress of PAI obviously degrade. After the patients that the adverse reaction of bleeding after IUD placement healing well or improved,the patho-damagement of the endometria’s obviously relieved,the disturbance of stripping or recovery endometria’s vanished or lightened;although the empress of ER、PR、VEGF、t-PA and PAI appears the tendency of height or degrade,but out of synchronia vanished or improved. In the directions to the improvement endometria’s patho-damagement and the empress of ER、PR、VEGF、KDR、t-PA、PAI、Gongning granula obviously better than Indometacin(P>0.05).Animal experiment manifests that,Gongning granula and Indometacin can improve abnormal change of the uterus angioarchitecture in the rat which placed IUD,obviously at max-dosage group and mid-dosage group.
     Conclusion: The patients who have IUD bleeding side reaction have an obvious hindrance of endometria exfoliating/repairing periodically,Gongning granula adjusts and recovers the delivery of endometrium ER、PR、VEGF and their receptors KDR、t-PA、PAI and the abnormal construction of uterus vessels, by relieving the impair of endometrium tectology and ultrastructure , so as to adjust peeling and recovery endometrium foul-up of IUD bleeding side reaction. Gongning granula's clinical effect、effect on traditional medical syndrome and improvement of relative indexes of endometrium exfoliating/repairing foul-up excels to Indometacin obviously.
引文
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