不同来源间充质干细胞治疗小鼠放射性肺损伤的研究
发布时间：2018-08-05 20:31
【摘要】：放疗是胸部肿瘤有效的治疗手段,放射牲肺损伤则是常见的并发症。放射性肺损伤分为早期急性损伤及放疗3个月后发生的晚期损伤,严重影响患者的生活质量,甚至导致死亡。目前急性期损伤的治疗多用大剂量糖皮质激素对症处理,由此会引起糖尿病、股骨头坏死等严重并发症；晚期放射性肺损伤生过程相对缓慢,症状多在照射后3-6个月才明显,此时肺放射性纤维化已形成,最佳治疗时机已经错过,有效治疗很少。如果有早期预测指标,及时采取措施,则可减少放射性肺炎的发生。目前临床急需预防及治疗放射性肺损伤有效、低毒的手段,同时也需要有效、易行的预测指标。 间充质干细胞(mesenchymal stem cells, MSCs)是干细胞家族的重要成员,可取材于多种组织,包括小鼠骨片、骨髓、胚胎肺及背主动脉区等部位,同时人源性MSC的研究也越来越多,如人脐带、羊膜等来源。MSC在体内或体外特定的诱导条件下,可诱导分化为脂肪、软骨、心肌以及肺上皮等多种组织细胞,其免疫调控作用也受到重视。 本研究目的是分离、培养出鼠源及人源不同取材部位的MSC,并将MSC输注给放射性肺损伤的小鼠模型,在不同时间点对比疗效,探索多种观察指标,为MSC用于放射肺损伤的临床治疗提供参考。 一、本研究首先从小鼠骨髓、胚肺及胚胎背主动脉区分离、培养MSCs,比较MSC对小鼠放射性肺损伤的治疗作用。将25只8-10周龄C57BL/6雌鼠分为5组：正常组、单照组、骨髓MSC治疗组、胚肺MSC治疗组、胚胎背主动脉(DA)区来源MSC治疗组,观察照射后5个不同时间点(照射后4周、9周、13周、17周、23周)各组小鼠外观、肺组织的病理变化。小鼠胸部照射剂量为单次18Gy。结果：小鼠外观评分均值顺序为正常组(10±0分)、DA组(8±0.71分)、胚肺组(7.6±0.57分)、骨髓组(6.1±1.75分)、对照组(4.8±0.84分),正常组明显好于各组,均为p0.01,单纯放疗组明显差于DA组、肺MSC组,均为p0.01。DA组、肺MSC组及骨髓组的两两配对t检验均为p0.05。肺病理镜检肺损伤评分均值由好到差的顺序为：正常组(0.12±0.16)、肺MSC组(0.22±0.1)、骨髓MSC组(0.33±0.18)、DA组(0.35±0.18)、对照组(0.54±0.27)。肺病理图像分析肺间质面积所占比例由好到差顺序为：正常组(64.3±1.6)、肺MSC组(76.1±2.8)、DA组(76.8±3.3)、骨髓MSC组(77.2±2.7)、对照组(80.8±3.5)。外观评分与病理镜检的相关性检验p=0.040,与图像分析的相关性检验p=0.039。结论：不同鼠源MSC均有减轻放射性肺损伤的作用,其作用效果相似,胚肺、DA区来源的略好。 二、本部分研究对鼠源MSC的治疗作用进行验证,同时检测了血液及肺组织的指标。将40只8-10周龄C57BL/6雌鼠随机平均分为4组(正常对照组、单纯照射组、胚肺MSC治疗组、DA区MSC治疗组),在两个时间点(4、8周)检测。小鼠胸部照射剂量为单次18Gy。观察小鼠外观并评分,光镜下观察肺损伤情况。用ELISA法检测小鼠血浆中TGF-β、IL-6的水平,并检测肺组织中羟脯氨酸的含量。结果：外观评分第4周时各组无显著差别,第8周时差别显著,其中正常组9.6±0.9,明显好于DA组(7.6±0.9,p=0.008)、胚肺组(7.8±0.4,p0.001)、单照组(6.6±0.5,p0.001),单照组差于DA组(p=0.066)、胚肺组(p=0.005),DA组与胚肺组相似(p=0.374)。病理检测评分第4周正常组0±0,明显好于DA组(0.19±0.05,p0.01)、胚肺组(0.29±0.22,p=0.019)、单照组(0.38±0.35,p0.001);第8周正常组为0.06±0.08,明显好于DA组(0.26±0.17,p=0.044)、胚肺组0.23±0.10,p=0.016)、单照组(0.30±0.18,p=0.025)。胚肺组、DA组、单照组的病理评分组间比较在第4周、第8周均无显著差异。IL-6水平(pg/ml)正常组(489.3±75.3、421.2±80.1)、单照组(437.9±87.1、398.1±116.3)在两个时间点的比较及组间比较均无显著差别。TGF-β1水平(pg/m1)正常组两个时间点分别为20.2±12.8、16.3±4.6,p=0.542;DA组值有下降,分别为27.5±13.5、12.4±2.6,p＝0.039；胚肺组分别为15.5±8.4、28.3±18.4,p=0.194;单照组分别为9.0±2.8、31.5±27.9,p=0.110。小鼠肺的羟脯氨酸含量(ng/ml)各组间差别不明显,各组4周时含量明显低于8周时含量,正常组分别为812.9±68.4、1080.8±189.5,p=0.018;DA组为823.3±14.6、1266.4±76.9,p0.01：胚肺组为796.2±62.7、1234±153.9,p0.001：单照组为839.0±17.0、1260.9±218.0,p=0.003。结论：小鼠不同来源MSC对放射性肺损伤有治疗作用,外观评分差异明显,病理评分中仅正常组显著好于其他组,其他各组间比较差异不显著,TGF-β1及IL-6检测有待进一步研究,羟脯氨酸水平随时间的变化明显升高,反应了肺损伤后期纤维化情况。 三、分离、培养人羊膜间充质干细胞(amnion MSC, AMSC)及脐带(umbilical cord MSC, UMSC),并进行表型鉴定。分别将AMSC及UMSC移植给胸部照射的小鼠观察疗效。共46只8-10周龄C57BL/6雌鼠分为4组、两个时间点(7周及11周),正常对照组11只(5+6)、单纯照射组(5+6)、人羊膜MSC治疗组(AMSC组)(7+8)、人脐带MSC治疗组(UMSC组)(4+5)。小鼠胸部剂量为单次20Gy。通过外观及病理表现比较各组的损伤情况,并用CBA法检测血浆中不同时间点的多种细胞因子,包括IL-6、IL-I0、MCP-1等。结果：移植了人源MSC的小鼠均未出现意外死亡或其他不良事件,表明人源MSC对小鼠有很好的安全性。照射后第7周、11周外观评分正常组为9.8±0.4及10±0,明显好于单照组8.2±0.4及8.0±0、AMSC组8±0.6及7.8±0.5、UMSC组8.3±0.5及8.0±0.5。单照组、AMSC组及UMSC组间无显著差别。第7周、11周病理镜检评分正常组0.06±0.05及0.12±0.05、UMSC组0.11±0.01及0.12±0.04、AMSC组0.14±0.09及0.14±0.06、单照组0.18±0.06及0.19±0.08,统计学均无显著差别。 正常组的6种血浆细胞因子水平第11周与第7周相比均无显著差别。受照射的各组有多种细胞因子在第11周的血浆水平明显低于第7周的水平。第7周单照组的血浆细胞因子水平均明显升高于正常组,第11周各组间血浆因子水平均无显著差别。细胞因子水平的变化表明除正常组外,各组均出现了炎性反应。 本研究的创新点：1.用外观评分、肺组织病理及图像分析等综合方法判断小鼠肺损伤程度。2.发现鼠源MSC对放射性肺损伤有明确的治疗作用。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法检测血浆细胞因子是观察炎性反应较好的方法。5.成功建立了小鼠放射性肺损伤的模型,初步分析了影响因素。 总之,鼠源MSC对放射性肺损伤有明确的治疗作用。外观评分、病理表现及血液学检测可作为观察方法对照射损伤进行评估。人源MSC对小鼠有很好的安全性,疗效需要进一步确定。
[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.
【学位授予单位】：中国人民解放军军事医学科学院
【学位级别】：博士
【学位授予年份】：2012
【分类号】：R818
本文编号：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.
【学位授予单位】：中国人民解放军军事医学科学院
【学位级别】：博士
【学位授予年份】：2012
【分类号】：R818
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