不同來源間充質(zhì)干細(xì)胞治療小鼠放射性肺損傷的研究
發(fā)布時間：2018-08-05 20:31
【摘要】：放療是胸部腫瘤有效的治療手段,放射牲肺損傷則是常見的并發(fā)癥。放射性肺損傷分為早期急性損傷及放療3個月后發(fā)生的晚期損傷,嚴(yán)重影響患者的生活質(zhì)量,甚至導(dǎo)致死亡。目前急性期損傷的治療多用大劑量糖皮質(zhì)激素對癥處理,由此會引起糖尿病、股骨頭壞死等嚴(yán)重并發(fā)癥；晚期放射性肺損傷生過程相對緩慢,癥狀多在照射后3-6個月才明顯,此時肺放射性纖維化已形成,最佳治療時機(jī)已經(jīng)錯過,有效治療很少。如果有早期預(yù)測指標(biāo),及時采取措施,則可減少放射性肺炎的發(fā)生。目前臨床急需預(yù)防及治療放射性肺損傷有效、低毒的手段,同時也需要有效、易行的預(yù)測指標(biāo)。 間充質(zhì)干細(xì)胞(mesenchymal stem cells, MSCs)是干細(xì)胞家族的重要成員,可取材于多種組織,包括小鼠骨片、骨髓、胚胎肺及背主動脈區(qū)等部位,同時人源性MSC的研究也越來越多,如人臍帶、羊膜等來源。MSC在體內(nèi)或體外特定的誘導(dǎo)條件下,可誘導(dǎo)分化為脂肪、軟骨、心肌以及肺上皮等多種組織細(xì)胞,其免疫調(diào)控作用也受到重視。 本研究目的是分離、培養(yǎng)出鼠源及人源不同取材部位的MSC,并將MSC輸注給放射性肺損傷的小鼠模型,在不同時間點(diǎn)對比療效,探索多種觀察指標(biāo),為MSC用于放射肺損傷的臨床治療提供參考。 一、本研究首先從小鼠骨髓、胚肺及胚胎背主動脈區(qū)分離、培養(yǎng)MSCs,比較MSC對小鼠放射性肺損傷的治療作用。將25只8-10周齡C57BL/6雌鼠分為5組：正常組、單照組、骨髓MSC治療組、胚肺MSC治療組、胚胎背主動脈(DA)區(qū)來源MSC治療組,觀察照射后5個不同時間點(diǎn)(照射后4周、9周、13周、17周、23周)各組小鼠外觀、肺組織的病理變化。小鼠胸部照射劑量為單次18Gy。結(jié)果：小鼠外觀評分均值順序?yàn)檎＝M(10±0分)、DA組(8±0.71分)、胚肺組(7.6±0.57分)、骨髓組(6.1±1.75分)、對照組(4.8±0.84分),正常組明顯好于各組,均為p0.01,單純放療組明顯差于DA組、肺MSC組,均為p0.01。DA組、肺MSC組及骨髓組的兩兩配對t檢驗(yàn)均為p0.05。肺病理鏡檢肺損傷評分均值由好到差的順序?yàn)椋赫＝M(0.12±0.16)、肺MSC組(0.22±0.1)、骨髓MSC組(0.33±0.18)、DA組(0.35±0.18)、對照組(0.54±0.27)。肺病理圖像分析肺間質(zhì)面積所占比例由好到差順序?yàn)椋赫＝M(64.3±1.6)、肺MSC組(76.1±2.8)、DA組(76.8±3.3)、骨髓MSC組(77.2±2.7)、對照組(80.8±3.5)。外觀評分與病理鏡檢的相關(guān)性檢驗(yàn)p=0.040,與圖像分析的相關(guān)性檢驗(yàn)p=0.039。結(jié)論：不同鼠源MSC均有減輕放射性肺損傷的作用,其作用效果相似,胚肺、DA區(qū)來源的略好。 二、本部分研究對鼠源MSC的治療作用進(jìn)行驗(yàn)證,同時檢測了血液及肺組織的指標(biāo)。將40只8-10周齡C57BL/6雌鼠隨機(jī)平均分為4組(正常對照組、單純照射組、胚肺MSC治療組、DA區(qū)MSC治療組),在兩個時間點(diǎn)(4、8周)檢測。小鼠胸部照射劑量為單次18Gy。觀察小鼠外觀并評分,光鏡下觀察肺損傷情況。用ELISA法檢測小鼠血漿中TGF-β、IL-6的水平,并檢測肺組織中羥脯氨酸的含量。結(jié)果：外觀評分第4周時各組無顯著差別,第8周時差別顯著,其中正常組9.6±0.9,明顯好于DA組(7.6±0.9,p=0.008)、胚肺組(7.8±0.4,p0.001)、單照組(6.6±0.5,p0.001),單照組差于DA組(p=0.066)、胚肺組(p=0.005),DA組與胚肺組相似(p=0.374)。病理檢測評分第4周正常組0±0,明顯好于DA組(0.19±0.05,p0.01)、胚肺組(0.29±0.22,p=0.019)、單照組(0.38±0.35,p0.001);第8周正常組為0.06±0.08,明顯好于DA組(0.26±0.17,p=0.044)、胚肺組0.23±0.10,p=0.016)、單照組(0.30±0.18,p=0.025)。胚肺組、DA組、單照組的病理評分組間比較在第4周、第8周均無顯著差異。IL-6水平(pg/ml)正常組(489.3±75.3、421.2±80.1)、單照組(437.9±87.1、398.1±116.3)在兩個時間點(diǎn)的比較及組間比較均無顯著差別。TGF-β1水平(pg/m1)正常組兩個時間點(diǎn)分別為20.2±12.8、16.3±4.6,p=0.542;DA組值有下降,分別為27.5±13.5、12.4±2.6,p＝0.039；胚肺組分別為15.5±8.4、28.3±18.4,p=0.194;單照組分別為9.0±2.8、31.5±27.9,p=0.110。小鼠肺的羥脯氨酸含量(ng/ml)各組間差別不明顯,各組4周時含量明顯低于8周時含量,正常組分別為812.9±68.4、1080.8±189.5,p=0.018;DA組為823.3±14.6、1266.4±76.9,p0.01：胚肺組為796.2±62.7、1234±153.9,p0.001：單照組為839.0±17.0、1260.9±218.0,p=0.003。結(jié)論：小鼠不同來源MSC對放射性肺損傷有治療作用,外觀評分差異明顯,病理評分中僅正常組顯著好于其他組,其他各組間比較差異不顯著,TGF-β1及IL-6檢測有待進(jìn)一步研究,羥脯氨酸水平隨時間的變化明顯升高,反應(yīng)了肺損傷后期纖維化情況。 三、分離、培養(yǎng)人羊膜間充質(zhì)干細(xì)胞(amnion MSC, AMSC)及臍帶(umbilical cord MSC, UMSC),并進(jìn)行表型鑒定。分別將AMSC及UMSC移植給胸部照射的小鼠觀察療效。共46只8-10周齡C57BL/6雌鼠分為4組、兩個時間點(diǎn)(7周及11周),正常對照組11只(5+6)、單純照射組(5+6)、人羊膜MSC治療組(AMSC組)(7+8)、人臍帶MSC治療組(UMSC組)(4+5)。小鼠胸部劑量為單次20Gy。通過外觀及病理表現(xiàn)比較各組的損傷情況,并用CBA法檢測血漿中不同時間點(diǎn)的多種細(xì)胞因子,包括IL-6、IL-I0、MCP-1等。結(jié)果：移植了人源MSC的小鼠均未出現(xiàn)意外死亡或其他不良事件,表明人源MSC對小鼠有很好的安全性。照射后第7周、11周外觀評分正常組為9.8±0.4及10±0,明顯好于單照組8.2±0.4及8.0±0、AMSC組8±0.6及7.8±0.5、UMSC組8.3±0.5及8.0±0.5。單照組、AMSC組及UMSC組間無顯著差別。第7周、11周病理鏡檢評分正常組0.06±0.05及0.12±0.05、UMSC組0.11±0.01及0.12±0.04、AMSC組0.14±0.09及0.14±0.06、單照組0.18±0.06及0.19±0.08,統(tǒng)計(jì)學(xué)均無顯著差別。 正常組的6種血漿細(xì)胞因子水平第11周與第7周相比均無顯著差別。受照射的各組有多種細(xì)胞因子在第11周的血漿水平明顯低于第7周的水平。第7周單照組的血漿細(xì)胞因子水平均明顯升高于正常組,第11周各組間血漿因子水平均無顯著差別。細(xì)胞因子水平的變化表明除正常組外,各組均出現(xiàn)了炎性反應(yīng)。 本研究的創(chuàng)新點(diǎn)：1.用外觀評分、肺組織病理及圖像分析等綜合方法判斷小鼠肺損傷程度。2.發(fā)現(xiàn)鼠源MSC對放射性肺損傷有明確的治療作用。3.人源MSC移植于普通的C57BL/6小鼠后有很好的安全性。4.用CBA法檢測血漿細(xì)胞因子是觀察炎性反應(yīng)較好的方法。5.成功建立了小鼠放射性肺損傷的模型,初步分析了影響因素。 總之,鼠源MSC對放射性肺損傷有明確的治療作用。外觀評分、病理表現(xiàn)及血液學(xué)檢測可作為觀察方法對照射損傷進(jìn)行評估。人源MSC對小鼠有很好的安全性,療效需要進(jìn)一步確定。
[Abstract]:Radiotherapy is an effective treatment for chest tumors, and radionuclide injury is a common complication. Radioactive lung injury is divided into early acute injury and late injury after 3 months of radiotherapy, which seriously affects the quality of life of the patients and even causes death. At present, the treatment of acute phase injury is mainly treated with large dose glucocorticoid. This will cause serious complications such as diabetes and necrosis of the femoral head; the process of late radiation lung injury is relatively slow and the symptoms are more obvious after 3-6 months of irradiation. At this time, the lung radiation fibrosis has formed, the best treatment time has been missed, and the effective treatment is very few. If an early prediction index is taken, the radioactivity can reduce the radioactivity. The occurrence of pneumonia. At present, it is urgent to prevent and treat radiation-induced lung injury by effective, low-toxic means, but also the need for effective, easy to predict indicators.
Mesenchymal stem cells (MSCs) is an important member of the stem cell family, which can be derived from a variety of tissues, including bone slices, bone marrow, embryonic lung and dorsal aorta, and more and more human MSC studies, such as human umbilical cord and amniotic membrane, can be induced under specific induction conditions in vivo or in vitro. The differentiation of cells into adipose tissue, cartilage, myocardium and lung epithelium has also been emphasized.
The purpose of this study is to isolate and cultivate the MSC of the rat source and the different parts of the source of human origin, and to transfuse MSC to the mice model of radionuclide injury, to compare the curative effect at different time points and to explore a variety of observation indexes to provide reference for the clinical treatment of radiation lung injury by MSC.
First, the study was separated from mouse bone marrow, embryo lung and embryonic dorsal aorta, and MSCs was cultured to compare the therapeutic effect of MSC on radiation lung injury in mice. 25 8-10 weeks old C57BL/6 female rats were divided into 5 groups: normal group, single illumination group, bone marrow MSC treatment group, embryo lung MSC treatment group, DA region source MSC treatment group, and 5 after irradiation. At different time points (4 weeks, 9 weeks, 13 weeks, 17 weeks, 23 weeks), the appearance of mice and the pathological changes of lung tissue were observed. The dose of chest irradiation in mice was the result of single 18Gy.: the order of appearance score of mice was normal group (10 + 0), DA group (8 + 0.71), Embryo Lung Group (7.6 + 0.57), bone marrow group (6.1 + 1.75), control group (4.8 + 0), normal group. Obviously better than all groups, all were P0.01, the radiotherapy group was significantly worse than the group DA, the lung MSC group was all p0.01.DA, the 22 paired t test of the MSC group and the bone marrow group were all p0.05. lung pathological examination in the normal group (0.12 + 0.16), the lung MSC group (0.22 + 0.1), the bone marrow MSC group (0.33 + 0.18), DA group (0.35 + 0.18), (0.35 + 0.18), and Group (0.54 + 0.27). Pulmonary pathological image analysis of the proportion of pulmonary interstitial area from good to poor order: normal group (64.3 + 1.6), lung MSC group (76.1 + 2.8), group DA (76.8 + 3.3), bone marrow MSC group (77.2 + 2.7), control group (80.8 + 3.5). Correlation test of appearance score and pathological examination p=0.040, and correlation test of image analysis with p=0.039. conclusion: p=0.039.: MSC from different sources reduced radioactivity lung injury, and its effect was similar. The origin of embryo lung and DA area was slightly better.
Two, this part of the study verified the therapeutic effect of rat MSC and detected the indexes of blood and lung tissue. 40 8-10 weeks old C57BL/6 female rats were randomly divided into 4 groups (normal control group, simple irradiation group, embryo lung MSC treatment group, DA region MSC treatment group), and two time interval (4,8 week) detection. The dose of mouse chest irradiation was single 18Gy.. The appearance and score of mice were observed and lung injury was observed under light microscope. The level of TGF- beta and IL-6 in the plasma of mice was detected by ELISA and the content of hydroxyproline in lung tissue was detected. Results: there was no significant difference between the groups at fourth weeks, and the difference was significant at eighth weeks, among which the normal group was 9.6 + 0.9, obviously better than the group DA (7.6 + 0.9, p=0.008), embryo lung. Group (7.8 + 0.4, p0.001), single group (6.6 + 0.5, p0.001), single illumination group was worse than group DA (p=0.066), Embryo Lung Group (p=0.005), DA group was similar to Embryo Lung Group (p=0.374). Pathological examination score was 0 + 0 in normal group fourth weeks, obviously better than DA group (0.19 + 0.05, P0.01), Embryo Lung Group (0.29 + 0.22, p=0.019), single illumination group (0.38 + 0.35, p0.001); eighth Zhou Zhengchang group It was better than group DA (0.26 + 0.17, p=0.044), Embryo Lung Group 0.23 + 0.10, p=0.016), single illuminated group (0.30 + 0.18, p=0.025). The comparison of pathological scores between the embryo lung group, DA group and single photo group was fourth weeks, and there was no significant difference in.IL-6 level (489.3 + 75.3421.2 + 80.1) in the normal group (489.3 + 75.3421.2 + 80.1) at eighth weeks, and the comparison of the single illumination group (437.9 + 87.1398.1 + 116.3) at the two time points. There was no significant difference in.TGF- beta 1 (pg/m1) normal group at two time points, respectively, 20.2 + 12.8,16.3 + 4.6, p=0.542, and DA group was 27.5 + 13.5,12.4 + 2.6, P = 0.039, and 15.5 + 8.4,28.3 + 18.4 and p=0.194 in Embryo Lung Group, respectively. The hydroxyproline content of lung of p=0.110. mice was 9 + 2.8,31.5 + 27.9, respectively. (ng/ml) the difference was not obvious in each group. The content of each group at 4 weeks was significantly lower than that of 8 weeks. The normal group was 812.9 + 68.41080.8 + 189.5, p=0.018, and DA group was 823.3 + 14.61266.4 76.9, P0.01: the embryo lung group was 796.2 + 62.71234 + 153.9, p0.001: the single photo group was 839 + 17.01260.9 + 218, p=0.003. conclusion: the mice from different sources MSC pairs Radiative lung injury has therapeutic effect, and the difference of appearance score is obvious. Only normal group in pathological score is better than other groups. There is no significant difference between other groups. TGF- beta 1 and IL-6 detection need to be further studied. The level of hydroxyproline is obviously increased with time, and it reacts with fibrosis in the later stage of lung injury.
Three, the human amniotic mesenchymal stem cells (amnion MSC, AMSC) and the umbilical cord (umbilical cord MSC, UMSC) were cultured and the phenotype was identified. AMSC and UMSC were transplanted to the mice of the chest irradiation. 46 8-10 week old female mice were divided into 4 groups, two time intervals (7 weeks and 11 weeks), 11 normal controls (5+6) and simple irradiation group (5+). 6) the human amniotic membrane MSC group (group AMSC) (group 7+8), human umbilical cord MSC treatment group (UMSC group) (4+5). The mice chest dose was single 20Gy. through the appearance and pathology of the injury, and the CBA method was used to detect a variety of cytokines at different time points in the plasma, including IL-6, IL-I0, MCP-1, etc. RESULTS: mice transplanted from human MSC were not out. Accidental death or other adverse events showed that human MSC had good safety in mice. Seventh weeks, 11 weeks after irradiation, the normal group was 9.8 + 0.4 and 10 + 0, obviously better than 8.2 + 0.4 and 8 + 0 in the single photo group. The group AMSC was 8 + 0.6 and 7.8 + 9.8. There was no significant difference between the group of AMSC and the UMSC group. The score in the normal group was 0.06 + 0.05 and 0.12 + 0.05 in the normal group. The group UMSC was 0.11 + 0.01 and 0.12 + 0.04, and the group AMSC was 0.14 + 0.09 and 0.14 + 0.06.
There was no significant difference in the level of 6 plasma cytokines in the normal group for eleventh weeks and seventh weeks. The plasma levels of various cytokines in each group were significantly lower than the level of seventh weeks at eleventh weeks. The level of plasma cytokines in the seventh week single group was significantly higher than that in the normal group, and there was no significant difference in plasma factor levels among the groups at eleventh weeks. Except for the normal group, inflammatory reaction was found in all groups.
The innovation points of this study: 1. using the appearance score, lung histopathology and image analysis to determine the degree of lung injury in mice.2. found that the rat source MSC has a definite therapeutic effect on the radiation lung injury..3. human MSC transplantation in the ordinary C57BL/6 mice has a good safety,.4. using CBA method to detect the plasma cytokines is to observe the inflammatory reaction In a better way,.5. successfully established a model of radiation lung injury in mice, and analyzed the influencing factors preliminarily.
In conclusion, rat MSC has a definite therapeutic effect on radionuclide injury. Appearance score, pathological manifestation and hematological detection can be used as an observation method to evaluate the radiation injury. Human MSC has good safety in mice and the effect needs to be further confirmed.
【學(xué)位授予單位】：中國人民解放軍軍事醫(yī)學(xué)科學(xué)院
【學(xué)位級別】：博士
【學(xué)位授予年份】：2012
【分類號】：R818
本文編號：2166934
[Abstract]:Radiotherapy is an effective treatment for chest tumors, and radionuclide injury is a common complication. Radioactive lung injury is divided into early acute injury and late injury after 3 months of radiotherapy, which seriously affects the quality of life of the patients and even causes death. At present, the treatment of acute phase injury is mainly treated with large dose glucocorticoid. This will cause serious complications such as diabetes and necrosis of the femoral head; the process of late radiation lung injury is relatively slow and the symptoms are more obvious after 3-6 months of irradiation. At this time, the lung radiation fibrosis has formed, the best treatment time has been missed, and the effective treatment is very few. If an early prediction index is taken, the radioactivity can reduce the radioactivity. The occurrence of pneumonia. At present, it is urgent to prevent and treat radiation-induced lung injury by effective, low-toxic means, but also the need for effective, easy to predict indicators.
Mesenchymal stem cells (MSCs) is an important member of the stem cell family, which can be derived from a variety of tissues, including bone slices, bone marrow, embryonic lung and dorsal aorta, and more and more human MSC studies, such as human umbilical cord and amniotic membrane, can be induced under specific induction conditions in vivo or in vitro. The differentiation of cells into adipose tissue, cartilage, myocardium and lung epithelium has also been emphasized.
The purpose of this study is to isolate and cultivate the MSC of the rat source and the different parts of the source of human origin, and to transfuse MSC to the mice model of radionuclide injury, to compare the curative effect at different time points and to explore a variety of observation indexes to provide reference for the clinical treatment of radiation lung injury by MSC.
First, the study was separated from mouse bone marrow, embryo lung and embryonic dorsal aorta, and MSCs was cultured to compare the therapeutic effect of MSC on radiation lung injury in mice. 25 8-10 weeks old C57BL/6 female rats were divided into 5 groups: normal group, single illumination group, bone marrow MSC treatment group, embryo lung MSC treatment group, DA region source MSC treatment group, and 5 after irradiation. At different time points (4 weeks, 9 weeks, 13 weeks, 17 weeks, 23 weeks), the appearance of mice and the pathological changes of lung tissue were observed. The dose of chest irradiation in mice was the result of single 18Gy.: the order of appearance score of mice was normal group (10 + 0), DA group (8 + 0.71), Embryo Lung Group (7.6 + 0.57), bone marrow group (6.1 + 1.75), control group (4.8 + 0), normal group. Obviously better than all groups, all were P0.01, the radiotherapy group was significantly worse than the group DA, the lung MSC group was all p0.01.DA, the 22 paired t test of the MSC group and the bone marrow group were all p0.05. lung pathological examination in the normal group (0.12 + 0.16), the lung MSC group (0.22 + 0.1), the bone marrow MSC group (0.33 + 0.18), DA group (0.35 + 0.18), (0.35 + 0.18), and Group (0.54 + 0.27). Pulmonary pathological image analysis of the proportion of pulmonary interstitial area from good to poor order: normal group (64.3 + 1.6), lung MSC group (76.1 + 2.8), group DA (76.8 + 3.3), bone marrow MSC group (77.2 + 2.7), control group (80.8 + 3.5). Correlation test of appearance score and pathological examination p=0.040, and correlation test of image analysis with p=0.039. conclusion: p=0.039.: MSC from different sources reduced radioactivity lung injury, and its effect was similar. The origin of embryo lung and DA area was slightly better.
Two, this part of the study verified the therapeutic effect of rat MSC and detected the indexes of blood and lung tissue. 40 8-10 weeks old C57BL/6 female rats were randomly divided into 4 groups (normal control group, simple irradiation group, embryo lung MSC treatment group, DA region MSC treatment group), and two time interval (4,8 week) detection. The dose of mouse chest irradiation was single 18Gy.. The appearance and score of mice were observed and lung injury was observed under light microscope. The level of TGF- beta and IL-6 in the plasma of mice was detected by ELISA and the content of hydroxyproline in lung tissue was detected. Results: there was no significant difference between the groups at fourth weeks, and the difference was significant at eighth weeks, among which the normal group was 9.6 + 0.9, obviously better than the group DA (7.6 + 0.9, p=0.008), embryo lung. Group (7.8 + 0.4, p0.001), single group (6.6 + 0.5, p0.001), single illumination group was worse than group DA (p=0.066), Embryo Lung Group (p=0.005), DA group was similar to Embryo Lung Group (p=0.374). Pathological examination score was 0 + 0 in normal group fourth weeks, obviously better than DA group (0.19 + 0.05, P0.01), Embryo Lung Group (0.29 + 0.22, p=0.019), single illumination group (0.38 + 0.35, p0.001); eighth Zhou Zhengchang group It was better than group DA (0.26 + 0.17, p=0.044), Embryo Lung Group 0.23 + 0.10, p=0.016), single illuminated group (0.30 + 0.18, p=0.025). The comparison of pathological scores between the embryo lung group, DA group and single photo group was fourth weeks, and there was no significant difference in.IL-6 level (489.3 + 75.3421.2 + 80.1) in the normal group (489.3 + 75.3421.2 + 80.1) at eighth weeks, and the comparison of the single illumination group (437.9 + 87.1398.1 + 116.3) at the two time points. There was no significant difference in.TGF- beta 1 (pg/m1) normal group at two time points, respectively, 20.2 + 12.8,16.3 + 4.6, p=0.542, and DA group was 27.5 + 13.5,12.4 + 2.6, P = 0.039, and 15.5 + 8.4,28.3 + 18.4 and p=0.194 in Embryo Lung Group, respectively. The hydroxyproline content of lung of p=0.110. mice was 9 + 2.8,31.5 + 27.9, respectively. (ng/ml) the difference was not obvious in each group. The content of each group at 4 weeks was significantly lower than that of 8 weeks. The normal group was 812.9 + 68.41080.8 + 189.5, p=0.018, and DA group was 823.3 + 14.61266.4 76.9, P0.01: the embryo lung group was 796.2 + 62.71234 + 153.9, p0.001: the single photo group was 839 + 17.01260.9 + 218, p=0.003. conclusion: the mice from different sources MSC pairs Radiative lung injury has therapeutic effect, and the difference of appearance score is obvious. Only normal group in pathological score is better than other groups. There is no significant difference between other groups. TGF- beta 1 and IL-6 detection need to be further studied. The level of hydroxyproline is obviously increased with time, and it reacts with fibrosis in the later stage of lung injury.
Three, the human amniotic mesenchymal stem cells (amnion MSC, AMSC) and the umbilical cord (umbilical cord MSC, UMSC) were cultured and the phenotype was identified. AMSC and UMSC were transplanted to the mice of the chest irradiation. 46 8-10 week old female mice were divided into 4 groups, two time intervals (7 weeks and 11 weeks), 11 normal controls (5+6) and simple irradiation group (5+). 6) the human amniotic membrane MSC group (group AMSC) (group 7+8), human umbilical cord MSC treatment group (UMSC group) (4+5). The mice chest dose was single 20Gy. through the appearance and pathology of the injury, and the CBA method was used to detect a variety of cytokines at different time points in the plasma, including IL-6, IL-I0, MCP-1, etc. RESULTS: mice transplanted from human MSC were not out. Accidental death or other adverse events showed that human MSC had good safety in mice. Seventh weeks, 11 weeks after irradiation, the normal group was 9.8 + 0.4 and 10 + 0, obviously better than 8.2 + 0.4 and 8 + 0 in the single photo group. The group AMSC was 8 + 0.6 and 7.8 + 9.8. There was no significant difference between the group of AMSC and the UMSC group. The score in the normal group was 0.06 + 0.05 and 0.12 + 0.05 in the normal group. The group UMSC was 0.11 + 0.01 and 0.12 + 0.04, and the group AMSC was 0.14 + 0.09 and 0.14 + 0.06.
There was no significant difference in the level of 6 plasma cytokines in the normal group for eleventh weeks and seventh weeks. The plasma levels of various cytokines in each group were significantly lower than the level of seventh weeks at eleventh weeks. The level of plasma cytokines in the seventh week single group was significantly higher than that in the normal group, and there was no significant difference in plasma factor levels among the groups at eleventh weeks. Except for the normal group, inflammatory reaction was found in all groups.
The innovation points of this study: 1. using the appearance score, lung histopathology and image analysis to determine the degree of lung injury in mice.2. found that the rat source MSC has a definite therapeutic effect on the radiation lung injury..3. human MSC transplantation in the ordinary C57BL/6 mice has a good safety,.4. using CBA method to detect the plasma cytokines is to observe the inflammatory reaction In a better way,.5. successfully established a model of radiation lung injury in mice, and analyzed the influencing factors preliminarily.
In conclusion, rat MSC has a definite therapeutic effect on radionuclide injury. Appearance score, pathological manifestation and hematological detection can be used as an observation method to evaluate the radiation injury. Human MSC has good safety in mice and the effect needs to be further confirmed.
【學(xué)位授予單位】：中國人民解放軍軍事醫(yī)學(xué)科學(xué)院
【學(xué)位級別】：博士
【學(xué)位授予年份】：2012
【分類號】：R818
【參考文獻(xiàn)】
相關(guān)期刊論文 前8條
1 王莉;方妮;張偉京;李秀森;劉兵;;骨實(shí)質(zhì)來源間質(zhì)干細(xì)胞對博萊霉素誘導(dǎo)小鼠肺損傷的保護(hù)作用[J];解放軍醫(yī)學(xué)雜志;2008年10期
2 申戈;陳冬波;賀文艷;孫慧茹;邵云;高嬌;周振山;劉兵;張偉京;;不同來源間充質(zhì)干細(xì)胞治療小鼠放射性肺損傷的研究[J];生物技術(shù)通訊;2012年02期
3 孫曉娟;楊乃龍;;成人與胎兒骨髓間充質(zhì)干細(xì)胞生物學(xué)性狀的比較[J];中國組織工程研究與臨床康復(fù);2009年14期
4 王曉燕,劉兵,苑春慧,要暉宇,毛寧;小鼠骨髓間充質(zhì)干細(xì)胞對胚胎干細(xì)胞造血分化的影響[J];中國實(shí)驗(yàn)血液學(xué)雜志;2003年04期
5 方妮;侯春梅;要暉宇;廖麗;賀文艷;張毅;毛寧;;小鼠胚胎AGM區(qū)永生化MSC樣基質(zhì)細(xì)胞的分離及其生物學(xué)特征[J];中國實(shí)驗(yàn)血液學(xué)雜志;2008年03期
6 趙路軍;王綠化;王小震;姬巍;朱向幟;楊偉志;殷蔚伯;;血液中TGF-β、IL-6及ACE含量在預(yù)測放射性肺炎中的價(jià)值[J];中華放射腫瘤學(xué)雜志;2006年03期
7 崔璦;代華平;戴建武;龐寶森;牛淑潔;呂月平;王辰;;骨髓間充質(zhì)干細(xì)胞對博來霉素致大鼠肺纖維化形成的影響[J];中華結(jié)核和呼吸雜志;2007年09期
8 徐新萍;王曉民;彭瑞云;王德文;;淺議信息可視化基本原理與應(yīng)用[J];中國體視學(xué)與圖像分析;2007年01期
，本文編號：2166934
本文鏈接：http://sikaile.net/yixuelunwen/yundongyixue/2166934.html
最近更新
教材專著
