本文選題：補(bǔ)腎法 + 疏肝法�。� 參考：《河北醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的:本研究通過觀察補(bǔ)腎法、疏肝法對超促排卵小鼠圍著床期子宮內(nèi)膜VEGFR-2及其下游血管生成MAPK家族信號通路的影響,以探討兩種方法改善子宮內(nèi)膜容受性的作用機(jī)制和環(huán)節(jié)之異同。方法:將240只動情周期正常的雌性小鼠隨機(jī)分為正常組、模型組、補(bǔ)腎組、疏肝組,每組各60只。除正常組外,各組建立控制性超促排卵小鼠模型。補(bǔ)腎組、疏肝組分別從造模第1天開始灌胃補(bǔ)腎助孕方混懸液和逍遙丸混懸液。模型組和正常組給予同等劑量蒸餾水灌胃,連續(xù)11天。正常組于動情期,模型組、補(bǔ)腎組、疏肝組于注射HCG日,按雌:雄=2:1比例合籠飼養(yǎng)。次日晨見陰栓記為孕1d,各組孕鼠分別于孕2d、3d、4d、5d、6d取材,通過放射免疫法檢測小鼠血清中雌二醇(E2)、孕酮(P)含量;采用HE染色觀察小鼠子宮內(nèi)膜厚度及形態(tài)學(xué)變化;掃描電鏡觀察小鼠子宮內(nèi)膜胞飲突的形態(tài),免疫組化法檢測小鼠子宮內(nèi)膜雌激素受體(ER)、孕激素受體(PR)、微血管密度(MVD)、VEGF、VEGFR-2、PCNA、CyclinD1、MMP-9蛋白表達(dá),Western Blot法檢測小鼠子宮內(nèi)膜ER、PR、PCNA、Cyclin D1、MMP-9、VEGF、VEGFR-2及其下游血管生成相關(guān)分子蛋白表達(dá),實時熒光定量PCR檢測VEGF、VEGFR-2、PCNA、CyclinD1、MMP-9mRNA表達(dá);統(tǒng)計比較各組小鼠陰栓率、妊娠率及胚胎著床數(shù)。結(jié)果:1各組小鼠陰栓率、妊娠率及胚胎著床數(shù)與正常組比較,模型組小鼠陰栓率、妊娠率均下降,胚胎著床數(shù)減少,差異有統(tǒng)計學(xué)意義(P0.05);與模型組相比,補(bǔ)腎組、疏肝組陰栓率、妊娠率均提高(均P0.05),且胚胎著床數(shù)增加(P0.05);補(bǔ)腎組陰栓率、妊娠率及胚胎著床數(shù)較疏肝組增加,但兩組比較無統(tǒng)計學(xué)意義(p0.05)。2圍著床期各組小鼠雌孕激素及其受體水平比較各組小鼠隨著妊娠天數(shù)的增加,血清e2、p值逐漸升高。孕第2、3、4、5、6天:與正常組比較,模型組小鼠血清e2值降低,差異有統(tǒng)計學(xué)意義(p0.05);與模型組比較,補(bǔ)腎組、疏肝組血清e2值升高(p0.05)。孕第3、5天補(bǔ)腎組血清e2值高于疏肝組,差異有統(tǒng)計學(xué)意義(p0.05),其余各天兩組比較無統(tǒng)計學(xué)差異(p0.05)。孕第2、3、4、5、6天:與正常組比較,模型組小鼠血清p值降低,差異有統(tǒng)計學(xué)意義(p0.05);與模型組比較,補(bǔ)腎組、疏肝組血清p值升高(p0.05);補(bǔ)腎組與疏肝組比較無明顯統(tǒng)計學(xué)差異(p0.05)。er、pr蛋白表達(dá)主要定位于小鼠子宮內(nèi)膜腺體、間質(zhì)的胞漿中。孕第2、3、4、5、6天:與正常組比較,模型組er、pr蛋白表達(dá)降低(p0.05);與模型組比較,補(bǔ)腎組、疏肝組er、pr蛋白表達(dá)升高(p0.05);補(bǔ)腎組與疏肝組之間比較表達(dá)無明顯差異(p0.05)。3圍著床期各組小鼠子宮內(nèi)膜厚度比較各組小鼠隨著妊娠天數(shù)的增加,子宮內(nèi)膜逐漸增厚。與正常組比較,模型組小鼠孕第2、3、4、5、6天子宮內(nèi)膜厚度均明顯降低(均p0.01);與模型組比較,補(bǔ)腎組、疏肝組孕第2、3、4、5、6天子宮內(nèi)膜厚度均顯著增加(均p0.01);補(bǔ)腎組與疏肝組比較,差異無統(tǒng)計學(xué)意義(p0.05)。4圍著床期各組小鼠子宮內(nèi)膜形態(tài)學(xué)變化he染色顯示:正常組:小鼠隨著妊娠天數(shù)的增加,子宮內(nèi)膜逐漸增厚;腺體數(shù)量增多,腺腔變大、彎曲,腺腔分泌物增多;間質(zhì)疏松水腫,基質(zhì)細(xì)胞增大,在孕第4天后宮腔逐漸閉合,基質(zhì)細(xì)胞增殖分化成蛻膜細(xì)胞。模型組:與正常組比較,子宮內(nèi)膜較薄且發(fā)育不良,腺體少而小,腺腔擴(kuò)張不明顯,腺腔分泌物較少;間質(zhì)疏松水腫,相對致密,部分小鼠子宮內(nèi)膜呈現(xiàn)腺體與間質(zhì)發(fā)育不同步,間質(zhì)呈分泌期改變而腺體發(fā)育仍為增生期。補(bǔ)腎組、疏肝組內(nèi)膜發(fā)育與正常組接近,優(yōu)于模型組,兩組間比較無明顯差異。5圍著床期各組小鼠子宮內(nèi)膜胞飲突的變化胞飲突主要分布于子宮內(nèi)膜腺體開口處。正常組:孕第3天,部分子宮內(nèi)膜細(xì)胞表面形成一些膜狀突起,突起表面有微絨毛覆蓋,絨毛短,稀疏,為發(fā)育中的胞飲突;孕第4天子宮內(nèi)膜表面有大量均勻分布、邊界清楚的膜狀突起,表面光滑,無微絨毛覆蓋,為完全發(fā)育的胞飲突;孕第5天胞飲突表面皺縮,凹陷,微絨毛重新出現(xiàn),為退化的胞飲突。模型組:孕第3天,胞飲突凸起較正常組明顯,微絨毛較短較稀疏,發(fā)育較正常組提前;孕第4天,子宮內(nèi)膜胞飲突數(shù)量較正常組減少,表面皺縮,大小不一,整體發(fā)育不同步,未見完全發(fā)育的胞飲突,提示胞飲突發(fā)育提前;孕第5天胞飲突皺縮較正常組明顯,微絨毛較少。補(bǔ)腎組、疏肝組:孕第3天,膜狀突起出現(xiàn),表面覆有微絨毛;孕第4天為完全發(fā)育的胞飲突,較模型組表面相對飽滿、分布相對均勻;孕第5天胞飲突發(fā)育與正常組接近,為退化的胞飲突。6免疫組織化學(xué)法檢測mvd在不同分組之間的比較cd34為血管密度標(biāo)志物,表達(dá)于子宮內(nèi)膜血管內(nèi)皮細(xì)胞,用于測定mvd。孕第2、3、4、5、6天:與正常組相比,模型組mvd明顯下降(p0.05);與模型組比較,補(bǔ)腎組、疏肝組mvd顯著增加(p0.05);與正常組比較,補(bǔ)腎組、疏肝組mvd降低(p0.05)。孕第6天,補(bǔ)腎組mvd高于疏肝組,差異有統(tǒng)計學(xué)意義(p0.05)。7免疫組織化學(xué)法檢測vegf、vegfr-2、pcna、cyclind1、mmp-9蛋白定位vegf、vegfr-2蛋白在圍著床期小鼠子宮內(nèi)膜的表達(dá)在空間上高度一致,主要定位在子宮內(nèi)膜腔上皮、腺上皮細(xì)胞、間質(zhì)細(xì)胞及血管內(nèi)皮細(xì)胞的胞漿中;pcna蛋白表達(dá)主要定位在子宮內(nèi)膜腔上皮、間質(zhì)細(xì)胞核內(nèi),腺上皮細(xì)胞核有少量表達(dá);cyclind1主要表達(dá)于子宮內(nèi)膜腔上皮、腺上皮的細(xì)胞核中,間質(zhì)細(xì)胞核內(nèi)表達(dá)較弱;mmp-9在子宮內(nèi)膜的腔上皮、腺上皮及間質(zhì)細(xì)胞漿中均有表達(dá)。8vegf、vegfr-2、pcna、cyclind1、mmp-9蛋白及其mrna時序表達(dá)規(guī)律孕第2天vegf、vegfr-2、pcna、cyclind1、mmp-9蛋白及其mrna表達(dá)較低,之后逐漸上升,于孕第4天達(dá)到峰值,與其他時間點比較差異有統(tǒng)計學(xué)意義(p0.05),之后表達(dá)逐漸下降。9vegf、vegfr-2、pcna、cyclind1、mmp-9蛋白及其mrna表達(dá)結(jié)果在不同分組之間的比較孕第2、3、4、5、6天:與正常組比較,模型組小鼠子宮內(nèi)膜vegf和vegfr-2蛋白及其mrna表達(dá)降低,差異有統(tǒng)計學(xué)意義(p0.05);與模型組相比,補(bǔ)腎組、疏肝組vegf、vegfr-2蛋白及其mrna表達(dá)明顯升高(p0.05)。但與正常組比較,孕第2、4、5、6天,補(bǔ)腎組、疏肝組vegf蛋白及其mrna表達(dá)降低(p0.05),孕第3、4、5、6天補(bǔ)腎組、疏肝組vegfr-2蛋白及其mrna表達(dá)降低(p0.05)。孕第6天補(bǔ)腎組vegf、vegfr-2蛋白及其mrna表達(dá)高于疏肝組,差異有統(tǒng)計學(xué)意義(p0.05),其余各天補(bǔ)腎組與疏肝組比較無統(tǒng)計學(xué)差異(p0.05)。孕第2、3、4、5、6天:與正常組比較,模型組小鼠子宮內(nèi)膜pcna蛋白及其mrna表達(dá)低于正常組,差異有統(tǒng)計學(xué)意義(p0.05);與模型組相比,補(bǔ)腎組、疏肝組pcna蛋白及其mrna表達(dá)明顯增多(p0.05)。孕第2、3、6天,補(bǔ)腎組與正常組比較無統(tǒng)計學(xué)差異(p0.05),孕第4、5天補(bǔ)腎組低于正常組,差異有統(tǒng)計學(xué)意義(p0.05)。孕第2、3、4、5天補(bǔ)腎組pcna蛋白及其mrna表達(dá)均高于疏肝組(p0.05)。孕第2、3、4、5、6天:與正常組相比,模型組小鼠子宮內(nèi)膜cyclind1蛋白及其mrna表達(dá)明顯低于正常組,差異有統(tǒng)計學(xué)意義(p0.05);與模型組相比,補(bǔ)腎組、疏肝組cyclind1蛋白及其mrna表達(dá)明顯升高(p0.05);補(bǔ)腎組、疏肝組低于正常組(p0.05),兩組間比較無統(tǒng)計學(xué)差異(p0.05)。孕第2、3、4、5、6天:與正常組比較,模型組小鼠子宮內(nèi)膜mmp-9蛋白及其mrna表達(dá)下降,差異有統(tǒng)計學(xué)意義(p0.05);與模型組相比,補(bǔ)腎組、疏肝組mmp-9蛋白及其mrna表達(dá)明顯升高(p0.05)。孕第2、3、4、5天補(bǔ)腎組低于正常組(p0.05),孕第2、4天疏肝組低于正常組(p0.05),孕第2、3、4、5天疏肝組高于補(bǔ)腎組(p0.05)。孕第6天,補(bǔ)腎組、疏肝組、正常組比較無統(tǒng)計學(xué)差異(p0.05)。10westernblot法檢測vegfr-2下游mapk家族信號通路蛋白表達(dá)孕2、3、4、5、6天:與正常組比較,模型組p-erk、p-p38、p-jnk蛋白表達(dá)降低(p0.05);與模型組比較,補(bǔ)腎組p-erk、p-p38、p-jnk蛋白表達(dá)升高(P0.05);疏肝組p-P38、p-JNK蛋白表達(dá)增強(qiáng),差異有統(tǒng)計學(xué)意義(P0.05),疏肝組p-ERK表達(dá)增強(qiáng),但差異無統(tǒng)計學(xué)意義(P0.05);疏肝組p-ERK蛋白表達(dá)較補(bǔ)腎組降低,差異有統(tǒng)計學(xué)意義(P0.05)。結(jié)論:1 VEGF參與胚泡著床且在圍著床期表達(dá)具有時空特異性,可作為子宮內(nèi)膜容受性評價指標(biāo)。2控制性超促排卵降低圍著床期小鼠血清E2、P水平,影響ER、PR表達(dá),使子宮內(nèi)膜腺體與間質(zhì)發(fā)育不同步,胞飲突發(fā)育提前,下調(diào)VEGF及其受體,降低微血管密度,影響VEGFR-2下游MAPK家族3條信號通路,降低通路活性,減少磷酸化ERK、P38、JNK的表達(dá),下調(diào)通路下游目的基因PCNA、CycinD1、MMP-9的表達(dá),影響子宮內(nèi)膜血管生成,降低子宮內(nèi)膜容受性,導(dǎo)致妊娠率、著床率降低。3補(bǔ)腎法、疏肝法通過改善超促排卵小鼠血清E2、P水平及ER、PR表達(dá),改善子宮內(nèi)膜形態(tài)及胞飲突發(fā)育,上調(diào)VEGF及其受體,改善微血管密度,調(diào)控VEGFR-2下游MAPK家族3條信號通路,增加通路活性,提高磷酸化ERK、P38、JNK的表達(dá),促進(jìn)通路下游目的基因PCNA、CycinD1、MMP-9的表達(dá),促進(jìn)細(xì)胞增殖遷移,有利于子宮內(nèi)膜血管生成,改善子宮內(nèi)膜容受性,從而提高小鼠妊娠率和著床率。4補(bǔ)腎法促進(jìn)磷酸化ERK表達(dá)優(yōu)于疏肝法;補(bǔ)腎法在促進(jìn)內(nèi)皮細(xì)胞增殖,加速血管生成,改善子宮內(nèi)膜容受性方面優(yōu)于疏肝法;疏肝法在水解細(xì)胞外基質(zhì)(extracellular matrix,ECM),促進(jìn)細(xì)胞遷移,促進(jìn)血管生成,改善子宮內(nèi)膜容受性方面優(yōu)于補(bǔ)腎法。
[Abstract]:Objective: To investigate the effect of two methods to improve the endometrial receptivity of the endometrium and the differences and similarities between the two methods to improve the endometrial receptivity of the endometrium and the MAPK family signal pathway of the endometrium in the surrounding bed of the superovulation mice. Methods: 240 female mice with normal estrus cycle were randomly divided into two groups. In the normal group, the model group, the kidney tonifying group and the Liver Soothing group, each group had 60 rats in each group. In addition to the normal group, the control superovulation mice model was established in each group. The tonifying kidney group and the liver Shugan group began to fill the kidney and the Xiaoyao suspension solution and the suspension of the Xiaoyao Pill from the model first days. The model group and the normal group were given the same dose of distilled water for 11 days. The model group, the kidney tonifying group and the liver Shugan group were fed on HCG day by female: male =2:1 ratio cage. The next morning, the female mice were pregnant with 2D, 3D, 4D, 5D, 6D, respectively. The content of estradiol (E2) and progesterone (P) in the serum of mice was detected by radioimmunoassay, and the endometrium thickness and morphological changes of mice were observed by HE staining; scan of the endometrium and morphology of mice by HE staining. The morphology of endometrium inrush in mouse endometrium was observed by electron microscopy. Immunohistochemistry was used to detect the estrogen receptor (ER), progesterone receptor (PR), microvascular density (MVD), VEGF, VEGFR-2, PCNA, CyclinD1, MMP-9 protein expression, and Western Blot method for detecting the endometrium of mice. The expression of relative molecular protein, VEGF, VEGFR-2, PCNA, CyclinD1 and MMP-9mRNA were detected by real time fluorescence quantitative PCR, and the negative emboli rate, pregnancy rate and embryo implantation number of the mice were compared. The results were as follows: 1 the rate of Yin embolism, the pregnancy rate and the number of embryo implantation were compared with those of the normal group. The difference was statistically significant (P0.05). Compared with the model group, the rate of Yin suppository in the kidney tonifying group, the Liver Soothing group increased (P0.05), and the number of embryo implantation increased (P0.05), the rate of Yin embolism in the kidney group, the pregnancy rate and the number of embryo implantation were higher than those in the Liver Soothing group, but the two groups were compared with the estradiol and the water progesterone and its receptor water in each group of.2 around the bed. As compared with the normal group, the serum E2 value of mice in the model group decreased and the difference was statistically significant (P0.05). Compared with the model group, the serum E2 value of the kidney group and the Liver Soothing group was higher (P0.05) than that in the model group (P0.05). The serum E2 value of the kidney tonifying group was higher than that of the Liver Soothing group at 3,5 day of pregnancy, and there was a difference between the group and the E2 group. Statistical significance (P0.05), the remaining days of the two groups had no statistical difference (P0.05). Gestation day 2,3,4,5,6: compared with the normal group, the serum P value of the model mice decreased, the difference was statistically significant (P0.05). Compared with the model group, the serum P value of the tonifying kidney group and the Liver Soothing group increased (P0.05), and there was no significant difference between the Bushen group and the Liver Soothing group (P0.05).Er (P0.05). The expression of PR protein was mainly located in the endometrium gland of mice and interstitial cytoplasm. Gestation day 2,3,4,5,6: compared with the normal group, the model group was Er, the expression of PR protein decreased (P0.05). Compared with the model group, the tonifying group, the Liver Soothing group Er, the PR protein expression increased (P0.05), and there was no significant difference between the tonifying group and the Liver Soothing group (P0.05).3 peri implantation period (P0.05). The endometrium thickness of the mice was compared with that of the normal group. Compared with the normal group, the endometrium thickness of the mice in the model group was significantly lower than that of the model group (all P0.01). The endometrium thickness of the tonifying group and the liver Shugan group increased significantly (all P0.01) on the day 2,3,4,5,6 of the model group (all P0.01); There was no significant difference between the kidney group and the liver dredging group (P0.05). The morphological changes of endometrium in each group of mice during the.4 implantation period he staining showed that in the normal group, the endometrium gradually thickened with the increase of the number of days of pregnancy; the number of glands increased, the gland cavity became larger, the secretion of the gland cavity increased, interstitial edema, the matrix cell enlargement, and the pregnancy. Fourth the cavity of the Thean Hou Temple was gradually closed and the matrix cells proliferated and differentiated into decidual cells. Compared with the normal group, the endometrium was thinner and dysplastic, the glands were small and small, the adeno cavity dilatated not obviously, the gland cavity was less secreted, the interstitium was loose edema and relatively compact, and the endometrium in some mice showed the dyssynchrony of glandular and interstitial development and the interstitium was divided. The endometrial development was close to the normal group, which was better than the model group. There was no significant difference between the two groups in the two groups. The changes of the endometrium drinking process in each group were mainly distributed at the opening of the endometrium. The normal group: third days of pregnancy and the surface of the endometrium cells. The formation of some membranous protuberances, the surface of the protuberance with microvilli, short villi and sparsely, for the development of the cell drink process; fourth days of pregnancy the endometrium surface has a large number of evenly distributed, clear boundary membrane, smooth surface, no microvilli cover, the complete development of the cell drink process; fifth days of pregnancy, the surface crinkle, sag, microvilli re appearance, In the model group, the model group: third days of pregnancy, the protrusion of the cytosolic protrusion was more obvious than the normal group, the microvilli was shorter and thinner and the development was earlier than the normal group; the number of endometrium inrush in the endometrium was less than the normal group at the fourth day of pregnancy. The surface of the endometrium was shrinking, the size was different, the whole development was not synchronized, and the development of the cytosolic process was not seen, suggesting that the development of the cytosolic process was ahead of time; fifth gestation was pregnant. Fifth pregnancy In the group of third days of pregnancy and the appearance of the membrane, the surface was covered with microvilli; the fourth day of pregnancy was a fully developed cytosolic process, which was relatively full and relatively uniform on the surface of the model group; the fifth day gestation was close to the normal group, which was a degraded.6 immunocytosochemistry of the degenerated cytosolic process. The comparison of MVD between different groups was detected by CD34 as a vascular density marker, expressed in endometrium vascular endothelial cells, and used to determine mvd. pregnancy 2,3,4,5,6 days: compared with the normal group, MVD was significantly decreased (P0.05). Compared with the model group, the MVD in the kidney group and the Liver Soothing group increased significantly (P0.05), and compared with the normal group, the kidney tonifying group and the Liver Soothing group MVD were compared with the normal group. Decrease (P0.05). Sixth days of pregnancy, the MVD of the tonifying group was higher than that of the Liver Soothing group. The difference was statistically significant (P0.05), the.7 immunohistochemical method was used to detect VEGF, VEGFR-2, PCNA, CyclinD1, and MMP-9 protein localization VEGF. The expression of VEGFR-2 protein in the endometrium of the mouse endometrium in the surrounding bed was consistent in space, mainly located in the endometrium epithelium, gland epithelial cells. The expression of PCNA protein is mainly located in the endometrium epithelium, interstitial nuclei, and a small amount of expression in the nucleus of the gland epithelium; CyclinD1 is mainly expressed in the endometrium epithelium, the nucleus of the gland epithelium, and the weak expression in the nucleus of the stromal cells; MMP-9 is in the cavity epithelium of the endometrium, and in the gland epithelium and between the epithelial cells. The expression of.8vegf, VEGFR-2, PCNA, CyclinD1, MMP-9 protein and mRNA was expressed in the cytoplasm of the cytoplasm at second days of VEGF, VEGFR-2, PCNA, CyclinD1, MMP-9 protein and its mRNA expression were low, then increased gradually, and reached the peak at the fourth day of pregnancy, and there was a significant difference compared with the other time points. Egfr-2, PCNA, CyclinD1, MMP-9 protein and mRNA expression results were compared between different groups on the day 2,3,4,5,6 day: compared with the normal group, the VEGF and VEGFR-2 protein and its mRNA expression in the endometrium of the model mice were reduced, and the difference was statistically significant (P0.05); the kidney group, the liver soothing group VEGF, the VEGFR-2 protein and its expression were compared with the model group. Xian Shenggao (P0.05). But compared with the normal group, the expression of VEGF protein and mRNA in the kidney group and the liver group decreased (P0.05), the VEGFR-2 protein and its mRNA expression in the liver group were decreased (P0.05). The VEGF, VEGFR-2 protein and mRNA expression of the kidney group were higher than those in the liver group at the sixth day of pregnancy, and the difference was statistically significant. There was no statistical difference between the kidney tonifying group and the liver dredging group (P0.05). 2,3,4,5,6 days of pregnancy: compared with the normal group, the expression of PCNA protein and mRNA in the endometrium of the model group was lower than that of the normal group, and the difference was statistically significant (P0.05). Compared with the model group, the expression of PCNA protein and mRNA in the tonifying group and the Shugan group increased significantly (P0.05). There was no statistical difference between the kidney tonifying group and the normal group (P0.05). The kidney tonifying group was lower than the normal group on the 4,5 day of pregnancy (P0.05). The expression of PCNA protein and mRNA in the kidney tonifying group on day 2,3,4,5 was higher than that in the Liver Soothing group (P0.05). Compared with the normal group, the difference was statistically significant (P0.05). Compared with the model group, the expression of cyclinD1 protein and its mRNA expression in the tonifying group and the Liver Soothing group increased significantly (P0.05); the kidney group and the Liver Soothing group were lower than the normal group (P0.05), and there was no statistical difference between the two groups (P0.05). Gestation 2,3,4,5,6 days: compared with the normal group, the endometrial MMP-9 protein in the model group mice was MMP-9 protein. And the expression of mRNA decreased, the difference was statistically significant (P0.05). Compared with the model group, the expression of MMP-9 protein and its mRNA in the tonifying group and the Liver Soothing group increased significantly (P0.05). The tonifying group was lower than the normal group (P0.05) on the 2,3,4,5 day of pregnancy (P0.05), and the Liver Soothing group was lower than the normal group (P0.05) on the 2,4 day of pregnancy (P0.05), and the sixth day of pregnancy was higher than that of the kidney tonifying group (P0.05). Group, Liver Soothing group, normal group had no statistical difference (P0.05).10westernblot method to detect VEGFR-2 downstream MAPK family signal pathway protein expression 2,3,4,5,6 days: compared with the normal group, the model group p-ERK, p-p38, p-JNK protein expression decreased (P0.05); compared with the model group, the kidney group p-ERK, p-p38, p-JNK protein expression increased. The expression of JNK protein was enhanced, the difference was statistically significant (P0.05), the expression of p-ERK in the Liver Soothing group was enhanced, but the difference was not statistically significant (P0.05). The expression of p-ERK protein in the Liver Soothing group was lower than that of the tonifying group (P0.05). Conclusion: 1 VEGF participates in the blastocyst implantation and has a spatio-temporal specificity in the peri bed period, which can be used as the endometrial receptivity. .2 controlled ovarian hyperstimulation decreased the serum E2 and P levels of the mice in the surrounding bed, and affected the ER, PR expression, which made the endometrial glands and interstitial development unsynchronized, the development of the cytoplasm of the cytosolic process early, down the VEGF and its receptor, reducing the microvessel density, affecting the 3 signal pathways of the VEGFR-2 downstream MAPK family, reducing the activity of the pathway and reducing the ERK, P38, J. The expression of NK, down regulation of the downstream target gene PCNA, CycinD1, MMP-9, affects the angiogenesis of the endometrium, reduces the endometrium receptivity, causes the pregnancy rate, reduces the implantation rate and reduces the.3 tonifying method. The Liver Soothing method improves the serum E2, P level and ER, PR expression in the superovulation mice, improves the morphology of endometrium and the development of the endometrium, up regulation of VEGF, and up regulation of VEGF and up regulation of VEGF. Its receptor, ameliorate microvascular density, regulate 3 signal pathways in the MAPK family of VEGFR-2 downstream, increase pathway activity, increase the expression of phosphorylated ERK, P38, JNK, promote the expression of PCNA, CycinD1, MMP-9, promote the proliferation and migration of the downstream target genes, promote the angiogenesis of endometrium, improve endometrial receptivity, and improve the pregnancy induced pregnancy induced pregnancy. The rate of pregnancy and the rate of implantation of.4 to promote the expression of phosphorylated ERK is better than that of the Liver Soothing method; the kidney tonifying method is superior to the Liver Soothing method in promoting the proliferation of endothelial cells, accelerating the angiogenesis and improving the receptivity of the endometrium; the Liver Soothing method is hydrolyzing the extracellular matrix (extracellular matrix, ECM), promoting the migration of the cells, promoting the angiogenesis and improving the receptivity of the endometrium. It is superior to the method of Tonifying the kidney.
【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R714.8

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