本文選題：子宮內(nèi)膜異位癥 + 血管生成　； 參考：《天津醫(yī)科大學(xué)》2014年碩士論文

【摘要】：目的：本實驗通過測定子宮內(nèi)膜異位癥(EMs, endometriosis)患者異位、在位、正常內(nèi)膜及不同時相的裸鼠異位病灶中周細(xì)胞數(shù)目(PN, Pericytes number)、微血管密度(MVD, microvessel density)以及PN/MVD：北值,研究探討周細(xì)胞在EMs血管生成中的作用。 方法：選取EMs患者異位內(nèi)膜20例(異位組)、在位內(nèi)膜40例(增殖期、分泌期各20例)(在位組)及非子宮內(nèi)膜異位癥患者子宮內(nèi)膜40例(增殖期、分泌期各20例)(對照組)。利用異體移植方法建立40只裸鼠人EMs模型,并隨機平均分為A組、B組、C組、D組,分別于建模后7天、14天、21天、28天時處死并獲取異位病灶。觀察裸鼠異位病灶肉眼及鏡下組織學(xué)形態(tài),并采用免疫組化法檢測三組人子宮內(nèi)膜及四組裸鼠異位病灶中PN、MVD的表達(dá),并對二者的比值(PN/MVD)進(jìn)行比較。 結(jié)果：(1)裸鼠EMs模型成功率達(dá)100%；(2)人異位內(nèi)膜MVD值高于正常內(nèi)膜和在位內(nèi)膜(P0.05),在位內(nèi)膜無論增殖期還是分泌期與相應(yīng)的正常內(nèi)膜相比差異均無統(tǒng)計學(xué)意義,在位內(nèi)膜及正常內(nèi)膜組內(nèi)比較均分泌期高于增殖期(P0.05)；(3)人異位內(nèi)膜PN值低于正常內(nèi)膜和在位內(nèi)膜(P0.05),在位內(nèi)膜無論增殖期還是分泌期與相應(yīng)的正常內(nèi)膜相比差異均無統(tǒng)計學(xué)意義,在位內(nèi)膜及正常內(nèi)膜組內(nèi)比較均增殖期高于分泌期(P0.05)；(4)人異位內(nèi)膜PN/MVD值低于正常內(nèi)膜和在位內(nèi)膜,在位內(nèi)膜無論增殖期還是分泌期均低于相應(yīng)的正常內(nèi)膜(P0.05),在位內(nèi)膜及正常內(nèi)膜組內(nèi)比較均增殖期高于分泌期(P0.05)；(5)A組裸鼠開腹探查見異位病灶呈清亮水皰狀,鏡下可見點簇狀新生血管形成,MVD=35.70±3.16, B組裸鼠開腹探查見異位病灶呈紅色囊泡狀,表面可見血管走形,鏡下可見腺體增生,間質(zhì)中血管生成明顯,MVD=68.60±9.07, C組裸鼠開腹探查見異位病灶呈暗紅色囊狀或結(jié)節(jié)狀,欠新鮮,鏡下可見腺體豐富、呈增殖期子宮內(nèi)膜表現(xiàn),間質(zhì)新生血管數(shù)目減少、血管壁結(jié)構(gòu)完整,MVD=53.50±3.57, D組裸鼠開腹探查見異位病灶呈黃白色囊狀或結(jié)節(jié)狀、質(zhì)稍硬,鏡下可見腺體數(shù)目減少,部分腺體及間質(zhì)纖維化,間質(zhì)新生血管數(shù)目進(jìn)一步減少,可見部分血管結(jié)構(gòu)破壞；MVD=48.00+4.99；四組裸鼠異位病灶MVD值差異具有統(tǒng)計學(xué)意義(P0.05)；(6)A-D組裸鼠異位病灶中PN與MVD的變化趨勢平行,分別為(27.30+2.50)、(79.40±10.68)、(64.70±4.64)、(38.30±4.50),差異均有統(tǒng)計學(xué)意義(P0.05)；(7)A-C組裸鼠PN/MVD值呈上升趨勢,在C組裸鼠異位病灶中達(dá)到峰值,D組裸鼠異位病灶中PN/MVD值同C組比較呈下降趨勢,但仍高于A組裸鼠,差異有統(tǒng)計學(xué)意義(P0.05)。 結(jié)論：(1)采用異體移植方法可在裸鼠體內(nèi)較完整地復(fù)制人類子宮內(nèi)膜異位癥,可實現(xiàn)對EMs發(fā)展過程的動態(tài)觀察及相關(guān)實驗研究,方法可行、成功率高,所得結(jié)果具有參考價值；(2)四組裸鼠異位病灶中PN值隨著病灶中血管的生長、消退發(fā)生相應(yīng)的改變,與相應(yīng)內(nèi)膜中MVD值變化趨勢相一致,提示周細(xì)胞在EMs血管生成中起著重要作用；(3)EMs患者異位內(nèi)膜中PN/MVD值低于在位和正常內(nèi)膜,C組裸鼠異位病灶中PN/MVD值達(dá)峰值,結(jié)合肉眼與鏡下所見,提示EMs病灶中周細(xì)胞覆蓋率與血管穩(wěn)定性高度一致性；(4)EMs患者在位內(nèi)膜無論增殖期還是分泌期中的PN/MVD值均低于相應(yīng)的正常內(nèi)膜,進(jìn)一步佐證了“在位內(nèi)膜決定論”,在位子宮內(nèi)膜中周細(xì)胞覆蓋率低可能是EMs發(fā)病的因素之一；(5)周細(xì)胞在EMs血管生成中的作用機制還有待進(jìn)一步研究。
[Abstract]:Objective: to determine the role of pericytes in EMs angiogenesis by measuring the number of pericytes (PN, Pericytes number), microvascular density (MVD, microvessel density) and PN/ MVD: the North value of ectopic and normal endometriosis (EMs, endometriosis) patients with heterotopic endometriosis, normal endometrium and different phase of nude mice.
Methods: 20 ectopic endometrium (ectopic endometrium) of EMs patients (ectopic endometrium), 40 cases of eutopic endometrium (proliferating, 20 secretory phase) and 40 non Endometriosis Endometrium endometrium (20 cases in the proliferation period and 20 secretory phase) were selected (control group). The EMs model of 40 nude mice was established by allograft transplantation, and was randomly divided into A group, B group, C group and D group. The expression of PN, MVD, and the expression of PN, MVD in the endometrium of three groups of human endometrium and four groups of nude mice were detected by immunohistochemical method, and the ratio of two (PN/MVD) was compared between the three groups of endometrium and four groups of nude mice.
Results: (1) the success rate of EMs model in nude mice was 100%. (2) the MVD value of ectopic endometrium was higher than normal endometrium and eutopic endometrium (P0.05). There was no statistical difference between the eutopic endometrium and the normal endometrium in the eutopic endometrium and the secretory phase. The secretory phase of the eutopic endometrium and the normal endometrium was higher than that in the proliferation period (P0.05); (3) the human ectopic endometrium was heterotopic. The PN value of the intima was lower than that of the normal intima and the eutopic endometrium (P0.05). There was no significant difference between the eutopic and secretory phase in the eutopic endometrium and the normal endometrium, in the eutopic endometrium and in the normal endometrium, the proliferation period was higher than that of the secretory phase (P0.05); (4) the PN/MVD value of the human endometrium was lower than that of the normal intima and the eutopic endometrium. The proliferation and secretory phase of the membrane were lower than that of the corresponding normal endometrium (P0.05), and the proliferation period in the eutopic endometrium and the normal endometrium was higher than that in the secretory phase (P0.05). (5) the open blistering of the A group in nude mice showed that the ectopic lesion showed a clear blister shape, the cluster shaped neovascularization was found under the microscope, MVD=35.70 + 3.16, and the open abdominal exploration of nude mice in group B was found to be ectopic disease. The focus was red vesicles, the surface of the blood vessel was visible, the glandular hyperplasia was seen under the microscope, the angiogenesis in the interstitium was obvious, MVD=68.60 + 9.07. C group nude mice open abdominal exploration showed that the ectopic lesion was dark red saclike or nodular, it was not fresh, the gland was abundant in the microscope, showed the endometrium in the proliferation stage, the number of interstitial neovascularization decreased and the vascular wall structure was reduced. Complete, MVD=53.50 + 3.57, D group nude mice open abdominal exploration showed that the ectopic lesion was yellow white cystic or nodular, slightly hard, the number of glandular decreased, some gland and interstitial fibrosis, the number of interstitial neovascularization was further reduced, and some vascular structure destruction; MVD= 48.00+4.99; the difference of MVD value of four groups of nude mice with heterotopic focus had unification. Study significance (P0.05); (6) the change trend of PN and MVD in the nude mice of A-D group was parallel, (27.30+2.50), (79.40 + 10.68), (64.70 + 4.64), (38.30 + 4.50), and the difference was statistically significant (P0.05). (7) the PN/MVD value of nude mice in the A-C group was up, reached the peak in the heterotopic nude mice of the C group, and the PN/MVD value of the nude mice in the D group was in the nude mice. Compared with group C, there was a downward trend, but it was still higher than that in group A, and the difference was statistically significant (P0.05).
Conclusions: (1) human endometriosis can be replicated completely in nude mice by allograft. The dynamic observation and related experimental study of EMs development process can be realized. The method is feasible, the success rate is high, and the results have reference value. (2) the value of PN in four groups of nude mice heterotopic focus decreases with the growth of the blood vessels in the lesion. The corresponding changes were consistent with the changes in the MVD values in the corresponding endometrium, suggesting that the pericytes play an important role in the angiogenesis of EMs; (3) the PN/MVD value in the ectopic endometrium of the EMs patients is lower than that in the eutopic and normal endometrium, and the peak value of the PN/MVD value in the ectopic lesion of the C group nude mice, combining with the naked eye and the mirror, suggests the coverage rate of the pericytes in the EMs focus. The high consistency of vascular stability; (4) the PN/MVD values in the eutopic endometrium of EMs patients are lower than that of the corresponding normal endometrium in both proliferative and secretory phase, which further confirms the "eutopic endometrial determinism". The low pericyte coverage rate in the eutopic endometrium may be one of the factors in the pathogenesis of EMs; (5) the role of pericytes in the angiogenesis of EMs. The mechanism remains to be further studied.
【學(xué)位授予單位】：天津醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R711.71

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本文編號：1969445