【摘要】：腫瘤相關巨噬細胞(TAMs)在調(diào)控Ⅰ型子宮內(nèi)膜癌雌激素敏感性中的作用及機制研究子宮內(nèi)膜癌(Endometrial carcinoma, EC)是女性最常見的生殖系統(tǒng)惡性腫瘤之一,其中70%-80%為Ⅰ型子宮內(nèi)膜樣腺癌,普遍認為其發(fā)生與長期無孕激素拮抗的雌激素刺激相關。我們的前期研究發(fā)現(xiàn),Ⅰ型子宮內(nèi)膜癌及其癌前病變患者血清雌激素水平并不高于健康同齡婦女,提示可能存在其他機制參與Ⅰ型內(nèi)膜癌的發(fā)生發(fā)展。對其他實體腫瘤的研究發(fā)現(xiàn),炎癥刺激在腫瘤的發(fā)生發(fā)展中起重要作用。大量流行病學研究發(fā)現(xiàn),Ⅰ型子宮內(nèi)膜癌與胰島素抵抗密切相關,而慢性炎癥是后者的重要臨床表現(xiàn)之一。也有研究顯示,作為慢性炎癥的具體表現(xiàn)形式,在子宮內(nèi)膜癌病灶存在巨噬細胞浸潤,后者與子宮內(nèi)膜癌的不良預后密切相關。提示巨噬細胞浸潤可能在Ⅰ型內(nèi)膜癌的發(fā)生發(fā)展中起重要作用。但其作用和機制還有待進一步研究。人體內(nèi)的單核/巨噬細胞可被誘導活化為不同表型：M1型和M2型,目前,M2型巨噬細胞被認為是在多數(shù)腫瘤中浸潤的巨噬細胞,也被稱為腫瘤相關巨噬細胞(Tumor-associated macrophages, TAMs)。以TAMs浸潤為主的炎癥反應與多種腫瘤的預后不良有關。研究發(fā)現(xiàn),巨噬細胞浸潤可調(diào)控腫瘤細胞激素受體的表達。在前列腺癌,巨噬細胞浸潤可上調(diào)雄激素受體表達,促進雄激素對前列腺的致癌作用。在乳腺癌,肥胖造成的慢性炎癥狀態(tài)可激活乳腺癌局部的雌激素受體。因此,我們推測子宮內(nèi)膜病灶局部TAMs浸潤可能通過調(diào)控雌激素受體,增加內(nèi)膜局部對雌激素的敏感性,促進癌癥的發(fā)生和發(fā)展。本研究擬通過分析巨噬細胞浸潤與子宮內(nèi)膜癌和癌前病變的相關性,以及巨噬細胞對子宮內(nèi)膜癌雌激素受體的調(diào)控及其對雌激素的敏感性,驗證上述假設,并進一步分析可能的機制所在。具體分為四部分：第一部分：Ⅰ型子宮內(nèi)膜癌及內(nèi)膜增生性病變患者血清雌激素水平分析；第二部分：巨噬細胞浸潤與Ⅰ型子宮內(nèi)膜癌及內(nèi)膜增生性病變的相關性分析；第三部分：TAMs通過ER α調(diào)控Ⅰ型子宮內(nèi)膜癌細胞雌激素敏感性；第四部分：TAMs通過IL-17調(diào)控Ⅰ型子宮內(nèi)膜癌細胞ER α表達。第一部分：Ⅰ型子宮內(nèi)膜癌及癌前病變患者血清雌激素水平分析目的：檢測血清雌激素水平與Ⅰ型子宮內(nèi)膜癌發(fā)生發(fā)展的相關性。方法：1.收集2011年9月至2013年12月,子宮內(nèi)膜正常及發(fā)生增生性病變患者的一般情況和血清雌二醇(Estradiol,E2)水平資料,包括對照組39例,增生紊亂69例,單純性增生過長168例,復雜性增生過長67例,不典型增生33例,Ⅰ型子宮內(nèi)膜癌25例,共收集病例401例。所有血液學檢測均在本院檢驗科執(zhí)行。統(tǒng)計分析血清雌激素水平,采用Graph pad prism 5.0軟件進行one-way ANOVA分析,以P=0.05為顯著性統(tǒng)計學差異標準。2.收集2011年9月至2013年12月,子宮內(nèi)膜正常及內(nèi)膜癌患者血清,包括對照組34例,Ⅰ型子宮內(nèi)膜癌34例,共收集病例68例。相同年齡正常及內(nèi)膜癌患者配對比較。ELISA檢測血清雌激素水平。采用Graph pad prism 5.0進行paired t test分析,以P=0.05為顯著性統(tǒng)計學差異標準。結(jié)果：1.臨床資料顯示,雌二醇水平在各組分布分別為：95.00±68.81ng/L、151.8±163.2 ng/L、156.4±178.8 ng/L、138.4±330.0 ng/L、125.5±156.7 ng/L、36.52 ±45.35 ng/L,結(jié)果不具有統(tǒng)計學差異(P0.05)。以40歲為界,將患者分為25-40歲和40-55歲兩個年齡段,25-40歲年齡段中,雌二醇水平在各組分布分別為：107.1 ±70.73 ng/L、140.3±165.2 ng/L、122.1±129.6 ng/L、76.59±59.86 ng/L和120.1±179.2 ng/L；40～55歲年齡段中,雌二醇水平在各組分布分別為：102.2±63.36 ng/L、 161.1±154.5 ng/L、164.0±20.6 ng/L、148.1±152.6 ng/L、148.3±122.5 ng/L和76.86±68.13 ng/L,同一年齡段的各組間雌二醇水平分布不具有統(tǒng)計學差異(P0.05)。2.Elisa結(jié)果顯示,雌二醇水平在對照組與Ⅰ型子宮內(nèi)膜癌組按同一年齡配對比較：P=0.8338,無統(tǒng)計學意義。結(jié)論：Ⅰ型子宮內(nèi)膜癌及癌前病變患者血清雌激素水平并不高于內(nèi)膜正常婦女。提示可能存在其他機制參與內(nèi)膜癌的發(fā)生發(fā)展。第二部分：巨噬細胞浸潤與Ⅰ型子宮內(nèi)膜癌及內(nèi)膜增生性病變的相關性分析目的：檢測巨噬細胞在Ⅰ型子宮內(nèi)膜癌及癌前病變中的浸潤情況,分析二者間的相關性。方法：收集正常及增生性病變子宮內(nèi)膜組織共140例：包括增殖期、分泌期、單純型增生、復雜型增生子宮內(nèi)膜各20例,不典型增生子宮內(nèi)膜、Ⅰ型子宮內(nèi)膜癌各30例,CD68免疫組化染色,計數(shù)各期別CD68(+)細胞數(shù),評價CD68(+)巨噬細胞在子宮內(nèi)膜中的浸潤情況。采用Graph pad prism 5.0進行one-way ANOVA分析,以P=0.05為顯著性統(tǒng)計學差異標準。結(jié)果：1.CD68表達于巨噬細胞的胞質(zhì)和胞膜。2.各組中CD68+細胞數(shù)目分別是(每400倍視野)：增殖期：6.641±5.463個：分泌期：13.82±10.36個；單純型增生：20.45±10.17個；復雜型增生：35.70±14.73個；不典型增生期：41.98±15.74個；Ⅰ型子宮內(nèi)膜癌：57.80±25.72個,與Ⅰ型子宮內(nèi)膜癌相比均有P0.001,CD68(+)細胞數(shù)與子宮內(nèi)膜增生性病變進展呈正相關。3.隨子宮內(nèi)膜增生性病變進展,巨噬細胞浸潤部位由血管周圍、間質(zhì)向腺上皮轉(zhuǎn)變。4.隨病變進展,巨噬細胞形態(tài)逐漸成熟。結(jié)論：CD68(+)巨噬細胞在子宮內(nèi)膜浸潤數(shù)目、部位及形態(tài)可能與Ⅰ子宮內(nèi)膜癌發(fā)生發(fā)展有關。第三部分：TAMs通過ERα調(diào)控Ⅰ型子宮內(nèi)膜癌細胞雌激素敏感性目的：研究TAMs在促進Ⅰ型子宮內(nèi)膜癌細胞增殖及內(nèi)膜癌細胞對雌二醇敏感性中的作用,并進一步分析可能的機制。方法：采用兩種雌激素受體陽性的子宮內(nèi)膜癌細胞株Ishikawa和HEC-1-A作為研究對象；培養(yǎng)單核細胞系THP-1,并誘導為M2型巨噬細胞,即TAMs;子宮內(nèi)膜癌細胞與M2型THP-1共培養(yǎng),或經(jīng)M2型THP-1的條件培養(yǎng)基培養(yǎng)后,CCK-8檢測共培養(yǎng)前后內(nèi)膜癌細胞增殖情況,以及對生理劑量(10-9M)E2的敏感性改變,并將此變化與過表達ERα或應用ER α抑制劑ICI后的趨勢相比較,采用Graph pad prism 5.0進行one-way ANOVA分析,以P=0.05為顯著性統(tǒng)計學差異標準；Real-time PCR和Western Blot檢測內(nèi)膜癌細胞與M2型THP-1共培養(yǎng)后雌激素受體α (ERα)的表達變化,并采用細胞增殖相關蛋白CyclinDl驗證細胞增殖情況。結(jié)果：1.人M2型THP-1巨噬細胞誘導活化成功,形態(tài)改變明顯,表型鑒定CD68、CD163、CD204和CD206顯著升高。2.M2型THP-1與Ⅰ型子宮內(nèi)膜癌細胞Ishikawa或HEC-1-A共培養(yǎng)后,內(nèi)膜癌細胞增殖均被促進；生理劑量的E2對兩株細胞的促增殖作用亦被上調(diào)；該現(xiàn)象可被雌激素受體抑制劑ICI抑制。3.M2型THP-1的條件培養(yǎng)基(CM)可時問依賴性促進Ishikawa和HEC-1-A細胞增殖,上調(diào)生理劑量雌激素對內(nèi)膜癌細胞的促增殖作用,其促增殖作用同樣可被ICI抑制。4.M2型THP-1的條件培養(yǎng)基(CM)可時間依賴性上調(diào)雌激素受體α表達,而對雌激素受體β無明顯作用；CM可時間依賴性上調(diào)cyclinDl表達；5.M2型THP-1對雌激素促增殖作用的上調(diào)作用與內(nèi)膜癌細胞過表達ER α后細胞增殖增強情況類似。結(jié)論：TAMs可促進子宮內(nèi)膜癌細胞Ishikawa和HEC-1-A增殖及對雌激素的敏感性,這種作用可能是通過上調(diào)內(nèi)膜癌細胞雌激素受體α實現(xiàn)的。第四部分：TAMs通過IL-17調(diào)控Ⅰ型子宮內(nèi)膜癌細胞ERα表達目的：篩選TAMs中可能在促進內(nèi)膜癌細胞增殖中起關鍵作用的炎癥因子,研究其在促Ⅰ型子宮內(nèi)膜癌細胞增殖及雌激素敏感性方面的作用,并探索可能的機制。方法：M2型THP-1與子宮內(nèi)膜癌細胞HEC-1-A經(jīng)Transwell共培養(yǎng)后,提取M2型THP-1細胞的RNA行Real-time PCR篩選穩(wěn)定作用的炎癥因子；采用CCK-8驗證篩選的炎癥因子對HEC-1-A的促增殖及促雌激素敏感性作用,采用Graph pad prism 5.0進行one-way ANOVA分析,以P=0.05為顯著性統(tǒng)計學差異標準；Real-time PCR和Western blot驗證該炎癥因子對HEC-1-A的ER α表達調(diào)控；Western blot驗證該炎癥因子和E2共同作用于HEC-1-A細胞后,對調(diào)控細胞增殖的p-AKT信號通路的活化作用。結(jié)果：1.經(jīng)篩選,與HEC-1-A共培養(yǎng)后M2型THP-1細胞炎癥因子IL-10和IL-17表達明顯增加；2.IL-10和IL-17均可上調(diào)E2對HEC-1-A細胞的促增殖作用,且IL-17作用更強；3IL-10、IL-17或E2處理后,均可上調(diào)HEC-1-A的ER a表達,且IL-17作用更強,進一步篩選出IL-17作為研究對象；4.IL-17與E2共同處理HEC-1-A細胞后,其p-AKT信號通路活化顯著增強,此作用與HEC-1-A細胞轉(zhuǎn)染過表達ERα后加用E2相似。結(jié)論：TAMs通過IL-17上調(diào)子宮內(nèi)膜癌細胞ER a的表達,從而促進內(nèi)膜癌細胞對雌激素敏感性增加,增強雌激素對內(nèi)膜癌細胞的促增殖作用。上述結(jié)果提示：1.血清雌激素水平與Ⅰ型子宮內(nèi)膜增生性病變的進展無顯著相關性,雌激素對內(nèi)膜的促癌作用可能存在其他機制；2.巨噬細胞浸潤與工型子宮內(nèi)膜增生性病變進展呈正相關,慢性炎癥可能在Ⅰ型子宮內(nèi)膜癌發(fā)生發(fā)展中發(fā)揮重要作用；3.腫瘤相關巨噬細胞通過上調(diào)內(nèi)膜癌細胞雌激素受體α表達增強雌激素對Ⅰ型子宮內(nèi)膜癌細胞的促增殖作用,慢性炎癥對雌激素敏感性的調(diào)控可能是Ⅰ型子宮內(nèi)膜癌發(fā)生發(fā)展的重要原因；4.腫瘤相關巨噬細胞通過分泌炎癥因子,如白介素-17,上調(diào)內(nèi)膜癌細胞雌激素受體α表達,從而提高內(nèi)膜細胞對雌激素敏感性�？赡苁莾�(nèi)膜癌發(fā)生發(fā)展的重要機制之一本課題研究表明：無孕激素拮抗的高雌激素水平可能不是雌激素促進Ⅰ型子宮內(nèi)膜癌發(fā)生的唯一方式,慢性炎癥調(diào)控的內(nèi)膜雌激素敏感性增加可能為內(nèi)膜癌發(fā)生的機制提供補充。靶向性抗炎治療可能為預防Ⅰ型子宮內(nèi)膜癌及癌前病變的發(fā)生提供新的思路。
[Abstract]:The role and mechanism of tumor-associated macrophages (TAMs) in regulating estrogen sensitivity in type I endometrial carcinoma Endometrial carcinoma (EC) is one of the most common female reproductive malignancies, 70% - 80% of which are type I endometrioid adenocarcinoma. It is generally believed that the occurrence of TAMs is associated with estrogen without progesterone antagonism for a long time. Our previous study found that serum estrogen levels in patients with type I endometrial carcinoma and its precancerous lesions were not higher than those in healthy women of the same age, suggesting that there may be other mechanisms involved in the development of type I endometrial carcinoma. A large number of epidemiological studies have found that type I endometrial carcinoma is closely related to insulin resistance, and chronic inflammation is one of the important clinical manifestations of the latter. It is suggested that macrophage infiltration may play an important role in the genesis and development of type I endometrial carcinoma, but its role and mechanism need to be further studied.Monocytes/macrophages in human body can be induced to activate into different phenotypes: M1 and M2. At present, M2 macrophages are considered as infiltrating macrophages in most tumors, also known as macrophages. Tumor-associated macrophages (TAMs). Inflammatory reactions predominantly with TAMs infiltration are associated with poor prognosis in a variety of tumors. Macrophage infiltration can regulate the expression of hormone receptors in tumor cells. In prostate cancer, macrophage infiltration can up-regulate the expression of androgen receptors and promote the effect of androgen on prostate. In breast cancer, chronic inflammation caused by obesity can activate estrogen receptor in breast cancer. Therefore, we speculate that local TAMs infiltration in endometrial lesions may promote the occurrence and development of cancer by regulating estrogen receptor and increasing local sensitivity to estrogen. The relationship between cell infiltration and endometrial carcinoma and precancerous lesions, and the regulation of macrophages on estrogen receptor and their sensitivity to estrogen in endometrial carcinoma were studied to verify the hypothesis and further analyze the possible mechanism. Analysis of serum estrogen level; Part II: Correlation between macrophage infiltration and type I endometrial carcinoma and endometrial hyperplasia; Part III: TAMs regulate estrogen sensitivity of type I endometrial carcinoma cells through ERalpha; Part IV: TAMs regulate ERalpha expression of type I endometrial carcinoma cells through IL-17. Objective: To detect the correlation between serum estrogen levels and the occurrence and development of type I endometrial carcinoma. Methods: 1. To collect the general information and serum estradiol (E2) of patients with normal and proliferative endometrium from September 2011 to December 2013. Data of serum estrogen levels were collected in 401 cases, including 39 cases of control group, 69 cases of hyperplasia disorder, 168 cases of simple hyperplasia, 67 cases of complex hyperplasia, 33 cases of atypical hyperplasia, 25 cases of type I endometrial carcinoma. E-way ANOVA analysis, with P = 0.05 as the significant statistical difference standard. 2. Collected from September 2011 to December 2013, normal endometrial and endometrial cancer patients serum, including 34 cases of control group, 34 cases of type I endometrial cancer, a total of 68 cases. The same age of normal and endometrial cancer patients matched comparison. ELISA detection of serum estrogen levels. Results: 1. The clinical data showed that the distribution of estradiol levels in each group were 95.00 (+ 68.81 ng/L), 151.8 (+ 163.2 ng/L), 156.4 (+ 178.8 ng/L), 138.4 (+ 330.0 ng/L), 125.5 (+ 156.7 ng/L) and 36.52 (+ 45.35 ng/L), respectively. The results were not statistically significant (P 0.05). 05). Patients were divided into 25-40 years old and 40-55 years old. The distribution of estradiol in each group was 107.1 (+ 70.73 ng/L), 140.3 (+ 165.2 ng/L), 122.1 (+ 129.6 ng/L), 76.59 (+ 59.86 ng/L) and 120.1 (+ 179.2 ng/L) in 25-40 years old, respectively. 63.36 ng/L, 161.1+154.5 ng/L, 164.0+20.6 ng/L, 148.1+152.6 ng/L, 148.3+122.5 ng/L and 76.86+68.13 ng/L. There was no significant difference in the distribution of estradiol levels among the same age groups (P 0.05). 2. Elisa results showed that estradiol levels in the control group and the type I endometrial cancer group were matched by the same age: P = 0.8338, no significant difference. Conclusion: The serum estrogen level of patients with type I endometrial carcinoma and precancerous lesions is not higher than that of normal endometrial women, suggesting that there may be other mechanisms involved in the occurrence and development of endometrial carcinoma. Methods: 140 normal and proliferative endometrial tissues were collected, including 20 cases of proliferative endometrium, 20 cases of simple hyperplasia, 20 cases of complex hyperplasia, 30 cases of atypical hyperplasia and 30 cases of type I endometrial carcinoma. The number of CD68 (+) cells in each stage was counted and the infiltration of CD68 (+) macrophages in endometrium was evaluated. Graph pad prism 5.0 was used for one-way ANOVA analysis. P = 0.05 was used as the standard of significant statistical difference. Results: 1. CD68 was expressed in the cytoplasm and membrane of macrophages. 2. The number of CD68 (+) cells in each group was separately analyzed. Proliferative phase: 6.641 + 5.463: Secretory phase: 13.82 + 10.36; Simple hyperplasia: 20.45 + 10.17; Complex hyperplasia: 35.70 + 14.73; Atypical hyperplasia: 41.98 + 15.74; Type I endometrial carcinoma: 57.80 + 25.72; Compared with type I endometrial carcinoma, there were all P 0.001, CD68 (+) cells and sons. With the development of endometrial hyperplasia, the infiltration sites of macrophages changed from perivascular to mesenchymal to glandular epithelial. 4. With the progress of endometrial hyperplasia, the morphology of macrophages gradually matured. Conclusion: The number, location and morphology of CD68 (+) macrophages infiltration in endometrium may be related to the occurrence of endometrial cancer. Part III: TAMs regulate estrogen sensitivity of type I endometrial carcinoma cells through ERalpha. Objective: To study the role of TAMs in promoting the proliferation of type I endometrial carcinoma cells and the sensitivity of endometrial carcinoma cells to estradiol, and to further analyze the possible mechanisms. Membrane cancer cell lines Ishikawa and HEC-1-A were used as research objects; monocyte THP-1 was cultured and induced into M2 macrophages, namely TAMs; endometrial cancer cells were co-cultured with M2 THP-1 or cultured on M2 THP-1 conditioned medium. CCK-8 was used to detect the proliferation of endometrial cancer cells before and after co-culture, and the sensitivity to physiological dose (10-9M) E2. The perceptual changes were compared with those after overexpression of ER-alpha or ICI. One-way ANOVA analysis was performed with Graph pad prism 5.0 and P=0.05 as the significant statistical difference standard. The expression of ER-alpha in endometrial carcinoma cells co-cultured with M2 THP-1 was detected by Real-time PCR and Western Blot. Results: 1. Human M 2 THP-1 macrophages were successfully induced and activated, and the morphological changes were obvious. The phenotypes of CD68, CD163, CD204 and CD206 were significantly increased. 2. M 2 THP-1 co-cultured with Ishikawa or HEC-1-A, the proliferation of endometrial cancer cells was promoted. Physiological dose of E2 also up-regulated the proliferation of the two cell lines; this phenomenon can be inhibited by estrogen receptor inhibitor ICI. 3. M2 THP-1 conditioned medium (CM) can promote the proliferation of Ishikawa and HEC-1-A cells in a time-dependent manner, and up-regulate the proliferation of endometrial cancer cells induced by physiological dose of estrogen, the same as its proliferation-promoting effect. Conditioned medium (CM) inhibited by ICI could up-regulate the expression of estrogen receptor alpha in a time-dependent manner, but had no significant effect on estrogen receptor beta; CM could up-regulate the expression of cyclin Dl in a time-dependent manner; 5. Conclusion: TAMs can promote the proliferation and estrogen sensitivity of endometrial carcinoma cells Ishikawa and HEC-1-A. This effect may be achieved by up-regulating estrogen receptor alpha in endometrial carcinoma cells. Part IV: TAMs regulate the expression of ERalpha in type I endometrial carcinoma cells through IL-17. Objective: To screen TAMs may promote the proliferation of endometrial carcinoma cells. Methods: M2 THP-1 and HEC-1-A cells were co-cultured with Transwell, and RNA of M2 THP-1 cells was extracted to screen stable inflammatory factors by Real-time PCR. Graph pad prism 5.0 was used for one-way ANOVA analysis, and P = 0.05 was used as the significant statistical difference standard; Real-time PCR and Western blot were used to verify the regulation of the inflammatory factors on the expression of ERalpha in HEC-1-A; Western blot was used to verify the inflammation. Results: 1. After co-culture with HEC-1-A, the expression of inflammatory factors IL-10 and IL-17 in M 2 THP-1 cells was significantly increased; 2. Both IL-10 and IL-17 could up-regulate the proliferation of HEC-1-A cells, and the effect of IL-17 was stronger. After treatment with IL-17 or E2, the expression of HEC-1-A was up-regulated, and the effect of IL-17 was stronger. IL-17 was further screened out as the research object. 4. After treatment with IL-17 and E2, the activation of p-AKT signaling pathway in HEC-1-A cells was significantly enhanced, which was similar to that of HEC-1-A cells transfected with ER-a and then treated with E2. These results suggest that: 1. There is no significant correlation between serum estrogen levels and the progression of type I endometrial hyperplasia, and estrogen may have other mechanisms to promote the proliferation of endometrial cancer cells. 2. Macrophage infiltration is positively correlated with the development of type I endometrial hyperplasia. Chronic inflammation may play an important role in the development of type I endometrial carcinoma. 3. Tumor-associated macrophages enhance the proliferation of type I endometrial carcinoma cells by up-regulating the expression of estrogen receptor alpha. The regulation of sex inflammation on estrogen sensitivity may be an important reason for the occurrence and development of type I endometrial carcinoma. This study suggests that high estrogen levels without progesterone antagonism may not be the only way estrogen promotes the development of type I endometrial carcinoma. Increased estrogen sensitivity in the endometrium regulated by chronic inflammation may complement the mechanism of endometrial carcinoma. Targeted anti-inflammatory therapy may prevent type I endometrial carcinoma and New ideas are provided for the occurrence of precancerous lesions.
【學位授予單位】：復旦大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R737.33

【相似文獻】

相關期刊論文 前10條

1 ;豚鼠巨噬細胞經(jīng)P_(204)處理后的抗石英細胞毒作用[J];國外醫(yī)學參考資料(衛(wèi)生學分冊);1976年04期

2 鄧俠進;;巨噬細胞的抗癌作用[J];遵義醫(yī)學院學報;1979年02期

3 陸天才;;疾病對肺巨噬細胞的影響[J];煤礦醫(yī)學;1982年01期

4 郭瑞清;祝彼得;;一種分離巨噬細胞的簡單方法[J];濱州醫(yī)學院學報;1990年02期

5 謝志堅;巨噬細胞異質(zhì)性[J];醫(yī)學綜述;2001年06期

6 饒艷;運動及神經(jīng)內(nèi)分泌對巨噬細胞功能的調(diào)節(jié)[J];體育與科學;2002年05期

7 朱金元;;吸煙對肺巨噬細胞的影響[J];浙江醫(yī)學教育;2003年01期

8 張俊峰;過氧化物酶體增殖物激活受體與單核/巨噬細胞系[J];醫(yī)學綜述;2004年03期

9 韋錦學;顧軍;;巨噬細胞的激活誘導死亡[J];生命科學;2006年02期

10 李曉曦;郭寧;曹雪濤;;腫瘤相關巨噬細胞促進腫瘤生長與轉(zhuǎn)移的研究現(xiàn)狀[J];中國腫瘤生物治療雜志;2008年01期

相關會議論文 前10條

1 史玉玲;王又明;豐美福;;巨噬細胞激活作用的研究[A];中國細胞生物學學會第五次會議論文摘要匯編[C];1992年

2 吳國明;周輝;;巨噬細胞和創(chuàng)傷纖維化[A];2009年浙江省骨科學學術(shù)年會論文匯編[C];2009年

3 李奇;王海杰;;透明質(zhì)酸對于淋巴結(jié)巨噬細胞運動的影響[A];解剖學雜志——中國解剖學會2002年年會文摘匯編[C];2002年

4 劉革修;歐大明;劉軍花;黃紅林;廖端芳;;丙丁酚在體外能抑制巨噬細胞脂質(zhì)氧化介導的低密度脂蛋白氧化并調(diào)節(jié)氧化巨噬細胞的分泌功能[A];面向21世紀的科技進步與社會經(jīng)濟發(fā)展（下冊）[C];1999年

5 葉金善;楊麗霞;郭瑞威;;環(huán)氧化酶-2/前列腺素E_2在血管緊張素Ⅱ刺激巨噬細胞表達細胞外基質(zhì)金屬蛋白酶誘導因子中的作用[A];第十三次全國心血管病學術(shù)會議論文集[C];2011年

6 秦帥;陳希;孔德明;;構(gòu)建由綠色熒光標記巨噬細胞的轉(zhuǎn)基因斑馬魚系[A];貴州省中西醫(yī)結(jié)合內(nèi)分泌代謝學術(shù)會論文匯編[C];2012年

7 武劍華;徐惠綿;;腫瘤相關巨噬細胞在胃癌中的相關研究[A];第9屆全國胃癌學術(shù)會議暨第二屆陽光長城腫瘤學術(shù)會議論文匯編[C];2014年

8 何軍;;血凝素樣氧化型低密度脂蛋白受體升高巨噬細胞內(nèi)膽固醇水平[A];中華醫(yī)學會第11次心血管病學術(shù)會議論文摘要集[C];2009年

9 宋盛;周非凡;邢達;;PDT誘導的凋亡細胞對巨噬細胞NO合成的影響[A];第七屆全國光生物學學術(shù)會議論文摘要集[C];2010年

10 張磊;朱建華;黃元偉;姚航平;;血管緊張素Ⅱ?qū)奘杉毎?THP-1重細胞)凝集素樣氧化低密度脂蛋白受體表達的影響[A];浙江省免疫學會第五次學術(shù)研討會論文匯編[C];2004年

相關重要報紙文章 前10條

1 通訊員 李靜 記者 胡德榮;惡性腫瘤巨噬細胞未必皆“惡人”[N];健康報;2014年

2 蘭克;以嘗試用巨噬細胞治癱瘓[N];科技日報;2000年

3 薛佳;免疫系統(tǒng)——人體的“衛(wèi)士”[N];保健時報;2009年

4 記者 胡德榮;鐵泵蛋白“維穩(wěn)”鐵代謝作用首次闡明[N];健康報;2011年

5 侯嘉 何新鄉(xiāng);硒的神奇功能[N];中國食品質(zhì)量報;2003年

6 唐穎 倪兵 陳代杰;巨噬細胞泡沫化抑制劑研究快步進行[N];中國醫(yī)藥報;2006年

7 劉元江;新發(fā)現(xiàn)解釋腫瘤為何易成“漏網(wǎng)之魚”[N];醫(yī)藥經(jīng)濟報;2007年

8 本報記者 侯嘉 通訊員 何新鄉(xiāng);今天你補硒了嗎[N];醫(yī)藥經(jīng)濟報;2003年

9 左志剛;升血小板藥使用注意[N];醫(yī)藥養(yǎng)生保健報;2007年

10 記者 許琦敏;“鐵泵”蛋白幫助回收鐵元素[N];文匯報;2011年

相關博士學位論文 前10條

1 周赤燕;巨噬細胞MsrA對動脈粥樣硬化的干預研究[D];武漢大學;2013年

2 章桂忠;TIPE2蛋白調(diào)控細胞增殖和炎癥的機制研究[D];山東大學;2015年

3 張瑜;DKK1抑制巨噬細胞內(nèi)脂質(zhì)沉積及其相關分子機制[D];山東大學;2015年

4 孟濤;異丙酚對心臟收縮功能的抑制作用及其對巨噬細胞分泌功能調(diào)節(jié)的機制研究[D];山東大學;2015年

5 周興;基于酵母微囊構(gòu)建新型口服巨噬細胞靶向遞送系統(tǒng)的研究[D];第三軍醫(yī)大學;2015年

6 蔣興偉;Tim-3對巨噬細胞極化的調(diào)控機制研究[D];中國人民解放軍軍事醫(yī)學科學院;2015年

7 劉伯玉;清道夫受體A介導小鼠巨噬細胞吞噬鉤端螺旋體研究[D];上海交通大學;2013年

8 楊紹俊;miRNA-155介導ESAT-6誘導巨噬細胞凋亡的分子機制及其在結(jié)核診斷中的作用[D];第三軍醫(yī)大學;2015年

9 翟光耀;單核/巨噬細胞Ly6C~(low)亞群在心肌梗死后瘢痕形成期的抗炎特性研究[D];北京協(xié)和醫(yī)學院;2014年

10 韓露;TRB3介導的脂肪組織巨噬細胞極化與糖尿病冠狀動脈病變關系的研究[D];山東大學;2015年

相關碩士學位論文 前10條

1 馬春梅;AP0E~(-/-)小鼠TLR9介導巨噬細胞極化效應對動脈粥樣硬化作用的研究[D];福建醫(yī)科大學;2015年

2 張譯丹;鹽皮質(zhì)激素受體拮抗劑調(diào)控巨噬細胞表型對實驗性矽肺的作用[D];河北醫(yī)科大學;2015年

3 盧文冉;HCV core蛋白作用的巨噬細胞培養(yǎng)上清對肝細胞生物學性狀的影響[D];河北醫(yī)科大學;2015年

4 李文建;載脂蛋白E影響巨噬細胞因子表達及分型的機制研究[D];河北醫(yī)科大學;2015年

5 曹爽;高糖對巨噬細胞TLR4信號轉(zhuǎn)導的調(diào)節(jié)作用[D];河北醫(yī)科大學;2015年

6 寧程程;腫瘤相關巨噬細胞在子宮內(nèi)膜癌雌激素敏感性中的作用及機制研究[D];復旦大學;2014年

7 高龍;PLD4在腫瘤相關巨噬細胞抑制結(jié)腸癌增殖中的作用研究[D];成都醫(yī)學院;2015年

8 任虹;感染期子宮頸癌U14細胞荷瘤小鼠抑制巨噬細胞CCL5分泌的機制研究[D];河北醫(yī)科大學;2015年

9 李美玲;雙酚A對小鼠腹腔巨噬細胞極化影響的體外研究[D];安徽醫(yī)科大學;2015年

10 劉瓊;黃芪多糖影響巨噬細胞向脂肪細胞趨化的作用及機制研究[D];新鄉(xiāng)醫(yī)學院;2015年

，

本文編號：2210628