本文選題：腎虛-薄型子宮內(nèi)膜　切入點：滋腎育胎丸　出處：《廣州中醫(yī)藥大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：目的:1.分析在滋腎育胎丸影響下,腎虛-薄型子宮內(nèi)膜不孕患者其月經(jīng)量、子宮內(nèi)膜厚度、中醫(yī)癥候的變化,探索中醫(yī)藥對薄型子宮內(nèi)膜的治療。分析在滋腎育胎丸影響下miR-135a、miR-196b對子宮內(nèi)膜HOXA10及其下游基因整合素β 3、EMX2基因的調(diào)控作用,以期闡明滋腎育胎丸治療薄型子宮內(nèi)膜的靶點及藥效機制,補充滋腎育胎丸的臨床適用范圍。方法:1.臨床實驗:選擇90例腎虛型-薄型子宮內(nèi)膜患者,采用隨機數(shù)字方法分為滋腎育胎丸組,戊酸雌二醇組,戊酸雌二醇+滋腎育胎丸組30例。戊酸雌二醇組于月經(jīng)第5日起予戊酸雌二醇2mg,日1次,連續(xù)10d;滋腎育胎丸組自月經(jīng)第5天開始予滋腎育胎丸,口服,淡鹽水或蜂蜜水送服。一次5克(約三分之二瓶蓋),一日3次。服用至月經(jīng)來潮停藥;戊酸雌二醇+滋腎育胎丸組予戊酸雌二醇+滋腎育胎丸加減,用量用法同前。三組皆以3個月為1療程,觀察三組臨床癥狀積分變化,月經(jīng)量變化,子宮內(nèi)膜厚度,妊娠率評估。2.動物實驗:將28只雌性SD大鼠隨機分為4組,分別為大鼠空白組,腎虛—薄型子宮內(nèi)膜大鼠空白組,腎虛—薄型子宮內(nèi)膜大鼠阿斯匹林組,腎虛—薄型子宮內(nèi)膜大鼠滋腎育胎丸組。予藥物干預(yù)后,應(yīng)用qRT-PCR檢測技術(shù),檢測大鼠子宮內(nèi)膜miR-135a、miR-196b、HOXA10基因、ITGβ 3基因、EMX2基因的表達變化。結(jié)果:1.中醫(yī)癥候積分比較,治療前三組中醫(yī)癥候積分比較無顯著性差異(P=0.6350.05),治療后有顯著性差異(P=0.0000.01),三組間治療前后積分差值有顯著性差異(P=0.0000.001)組內(nèi)自身治療前后積分比較均有顯著差異(P=0.0000.01)。2.中醫(yī)癥候綜合療效:90例病例中,西藥組總有效率為6.67%,中西醫(yī)組總有效率100%,中醫(yī)組總有效率70%。3.月經(jīng)改善情況:三組病例治療前后月經(jīng)量積分比較有顯著差異(t=-6.407,P=0.0000.01)。4.子宮內(nèi)膜厚度的改善:三組病例治療后子宮內(nèi)膜厚度均較治療前明顯增厚。5.造模組子宮內(nèi)膜EMX2基因表達較空白模型組、阿司匹林組、滋腎育胎丸組均增高(P0.05),而滋腎育胎丸組子宮內(nèi)膜EMX2基因表達較其余各組低(P0.05)。6.造模組整合素β 3基因表達較空白對照組、滋腎育胎丸組低(P0.05),滋腎育胎丸組整合素β 3表達較造模組、阿司匹林組表達高(P0.05)。7.滋腎育胎丸組的HOXA10基因相對表達量較空白模型組、阿司匹林組、造模組明顯偏高(P0.05),其中造模組的HOXA10基因相對表達量最低(P0.05)。8.與造模組比較,空白對照組,阿司匹林組,滋腎育胎丸組的miR-135a相對表達量均較造模組低,其中,滋腎育胎丸高劑量組的最低(P0.05)。9.與造模組比較,其余各組的miR-196b相對表達量均較造模組低(P0.05)。10.HOXA10基因與EMX2基因表達顯著負相關(guān)(r=-0.683,P0.01);HOXA10基因與ITGβ 3基因表達顯著正相關(guān)(r=0.714,P0.01)。11.miR-135a 與 HOXA10 基因負相關(guān)性(r=-0.683,P0.01);miR-135a 和 EMX2基因表達高度正相關(guān)(r=0.886,P0.01);miR-135a和ITGβ 3基因表達呈現(xiàn)顯著負相關(guān)(r=-0.722,P0.01)。12.miR-196b 與 HOXA10 基因表達呈顯著負相關(guān)(r=-0.736,P0.01);miR-196b 與 EMX2基因表達顯著相關(guān)(r=0.778,P0.01);miR-196b 和 ITGβ 3 基因表達呈現(xiàn)負負相關(guān)(r=-0.778,P0.01)。結(jié)論:1、本研究臨床觀察結(jié)果顯示滋腎育胎丸聯(lián)合雌激素能有效改善腎虛-薄型子宮不孕患者的子宮內(nèi)膜厚度,月經(jīng)量,中醫(yī)臨床癥狀等,其效果優(yōu)于單純使用雌激素治療。提示滋腎育胎丸通過補腎,對腎虛-薄型子宮不孕患者有治療作用。2、本研究動物實驗結(jié)果顯示滋腎育胎丸能增強大鼠子宮內(nèi)膜ITGβ 3、HOXA10基因的表達;其對EMX2、miR-135a、miR-196b基因抑制作用優(yōu)于阿司匹林組、雌激素組。提示滋腎育胎丸治療腎虛-薄型子宮內(nèi)膜大鼠,其可能通過下調(diào)miR-135a,miR-196b,上調(diào)HOXA10基因的表達,從而調(diào)節(jié)靶基因EMX2、ITGβ3,以此改善腎虛-薄型子宮內(nèi)膜大鼠的子宮內(nèi)膜容受性。
[Abstract]:Objective: to analysis the 1. effects of Zishen Yutai Pill on kidney deficiency, - thin endometrium of infertile patients with menstrual volume, endometrial thickness, change of TCM syndrome, to explore the traditional Chinese medicine therapy on thin endometrium. In the analysis of Zishenyutai pill under the influence of miR-135a, miR-196b on the uterus HOXA10 integrin and its downstream gene beta 3, regulation of EMX2 gene, in order to clarify the target of Zishenyutai pill in the treatment of thin endometrium and pharmacodynamics, clinical application of Zishenyutai pill. Methods: 1. clinical trials: 90 patients with kidney deficiency - thin endometrium patients were randomly into. Kidney Yutai pill group, estradiol valerate group, estradiol valerate + Zishenyutai pill group. 30 cases of estradiol valerate group on the fifth day of menstruation given estradiol valerate 2mg, 1 times a day, continuous 10d; Zishenyutai pill group from the fifth day of menstruation for Zishenyutai pill. Oral, Salt water or honey water delivery service. A 5 grams (about 2/3 bottle), 3 times a day. Take to menstrual withdrawal; estradiol valerate + Zishenyutai pill group were given estradiol valerate + Zishenyutai pill, usage as before. The three groups were both 3 months was 1 course of treatment, observe three groups of clinical symptom changes, menstrual changes, endometrial thickness and pregnancy rate assessment.2. animal experiment: 28 female SD rats were randomly divided into 4 groups, respectively. Rats in the blank group, deficiency of kidney - thin endometrium of rat blank group, deficiency of kidney - thin endometrium of rats in aspirin group kidney, kidney - thin endometrium of rat Yutai pill group. For drug intervention, application of qRT-PCR detection technology, detection of rat endometrial miR-135a, miR-196b, HOXA10 gene, ITG beta 3 gene expression of EMX2 gene. Results: compared with the integral 1. TCM symptoms in three groups before treatment, TCM syndrome integral comparison No significant difference (P=0.6350.05) after treatment, there was significant difference (P=0.0000.01), before and after treatment between the three groups of integral difference have significant difference (P=0.0000.001) significant differences within groups before and after treatment scores were (P=0.0000.01).2. TCM syndrome curative effect in 90 cases, western medicine group the total effective rate was 6.67%. Western medicine group the total efficiency of 100%, the total efficiency of TCM group 70%.3.: menstruation in three groups before and after the treatment of menstruation integral had significant difference (t=-6.407, P=0.0000.01).4. endometrial thickness improved: three groups of patients after treatment of endometrial thickness were significantly thickened.5. model of endometrial EMX2 gene expression compared with the model group, aspirin group, Zishenyutai pill group were increased significantly (P0.05), and Zishenyutai pill group endometrial EMX2 gene expression is low in other groups (P0.05).6. model of integrin beta 3 gene Expression compared with blank control group, Zishenyutai pill group (P0.05), Zishenyutai pill group of integrin beta 3 expression compared with the model group, the high expression of aspirin group (P0.05).7. Yu Zishen relative expression compared with the model group, HOXA10 gene of fetal pill group and aspirin group (model group was significantly higher P0.05), the HOXA10 gene expression of the model group (P0.05.8.) the lowest compared with the model group, blank control group, aspirin group, Zishenyutai pill group, the relative expression level of miR-135a was low compared with that in the model, the Zishenyutai pill high dose group (P0.05) compared with the lowest.9. the model group and the other groups of miR-196b expression were lower than model group (P0.05) and low expression of.10.HOXA10 gene and EMX2 gene significantly negative correlation (r=-0.683, P0.01); the expression of HOXA10 gene and ITG beta 3 gene significantly positive correlation (r=0.714, P0.01).11.miR-135a and HOXA10 gene negative correlation (r=-0.683, P0.01) MiR-135a; the expression of EMX2 gene and high positive correlation (r=0.886, P0.01); miR-135a and ITG beta 3 gene expression showed a significant negative correlation (r=-0.722, P0.01).12.miR-196b and HOXA10 gene expression were negatively correlated (r=-0.736, P0.01); the expression of miR-196b and EMX2 gene significantly correlated (r=0.778, P0.01); miR-196b and ITG beta a related expression showed 3 gene (r=-0.778, P0.01). Conclusion: 1. The study of the clinical observation showed that Zishenyutai pill combined with estrogen can effectively improve kidney - thin infertility uterine endometrial thickness, menstrual volume, clinical symptoms, the effect is better than the simple use of estrogen therapy. Tips for Zishenyutai the therapeutic effect of Bushen pill,.2 of kidney - thin uterine infertility patients, the study of animal experiment results show that Zishenyutai pill can enhance rat endometrial ITG beta 3, HOXA10 gene expression of EMX2, miR-135a; MiR-196b gene, inhibitory effect than aspirin group, estrogen group. Prompt treatment of kidney - nourishing kidney Yu Tai Wan thin endometrium of rats, which may be through the downregulation of miR-135a, miR-196b, up regulation of HOXA10 gene expression, thereby regulating the target gene EMX2, ITG beta 3, in order to improve the deficiency of the kidney - thin endometrium of rat uterine receptivity.

【學(xué)位授予單位】：廣州中醫(yī)藥大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R271.9

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