脂肪间充质干细胞对野百合碱诱发的大鼠肺动脉重构的影响

发布时间：2018-09-18 21:48

【摘要】：目的: 探讨脂肪间充质干细胞(ADMSC)移植治疗对野百合碱诱发的大鼠肺动脉高压肺血管重构的影响。 方法: 取SD大鼠腹股沟皮下脂肪,胶原酶消化法分离培养ADMSC,移植前用带GFP的腺病毒转染标记。雄性Sprague-Dawley大鼠90只,随机均分为三组,每组30只:正常对照组(Ctr)、肺动脉高压组(PAH)、脂肪间充质干细胞治疗组(ADMSC)。PAH组和ADMSC组一次性腹腔注射MCT40mg/Kg,Ctr组经腹腔注射相同体积的生理盐水,两周后ADMSC组经左颈外静脉一次性给予ADMSC 10~6/1ml,Ctr组和PAH组经左颈外静脉一次性给予1ml的生理盐水。分别于ADMSC移植后1W、2W、3W,右心导管法测定大鼠的肺动脉平均压(MPAP)、右心室肥厚指数[RVHI%=右心室游离壁(RV)重量/左心室+室间隔(LV+S)重量]、并运用ipp6.0图像分析软件分析肺组织切片,测定直径在100-200μm范围的肺小动脉管壁厚度(WT)占动脉外径(ED)的百分比(WT%)及管壁面积(WA)占血管总面积的百分比(WA%)。荧光显微镜观察带GFP标记的ADMSC在肺内的定植。 结果: (1)ADMSC治疗后1W,2W,3W,三个时间点,每一个时间点,PAH组大鼠与正常组相比,大鼠的MPAP和RVHI%均高于Ctr组[MPAP(mmHg): (24.53±2.90) VS (14.81±1.95),(33.18±2.30)VS(15.08±2.35),(36.38±3.28)VS(15.65±2.27);RVHI%:(41.01±1.29)VS(28.25±2.15),(48.75±2.13)VS(28.71±2.08),(50.52±1.49)VS(28.54±2.19);P均0.05]。而经ADMSC治疗后,MPAP和RVHI%较PAH组下降[MPAP(mmHg): (18.63±2.15) VS(24.53±2.90),(23.07±2.84)VS(33.18±2.30),(22.98±2.34)VS(36.38±3.28);RVHI%:(36.21±4.27)VS(41.01±1.29),(39.47±4.02)VS(48.75±2.13), (41.02±0.93)VS(50.52±1.49);P均0.05]。 (2)ADMSC治疗后1W,2W,3W,三个时间点,每一个时间点,PAH组大鼠与正常组相比,大鼠的WA%和WT%均明显高于Ctr组[WA%: (68.70±3.43) VS(50.27±4.92),(80.48±6.19)VS(51.61±3.29),(84.01±2.76)VS(52.02±5.87);WT%:(46.09±4.70)VS(32.46±5.19),(57.26±4.32)VS(32.52±3.19),(64.64±3.86)VS(31.42±4.53);P均0.05]。而经ADMSC治疗后,WA%和WT%均较PAH组下降[WA%:(58.23±4.08) VS(68.70±3.43),(62.97±6.58)VS(80.48±6.19),(65.27±5.45)VS(84.01±2.76);WT%:(38.06±4.15)VS(46.09±4.70),(40.91±5.24)VS(57.26±4.32), (41.91±5.16)VS(64.64±3.86);P均0.05]。 (3)与ADMSC治疗后1W比,ADMSC治疗后2W、3W,治疗组大鼠的MPAP、RVHI%、WA %和WT %均高[MPAP ( mmHg ):( 23.07±2.84 )、( 22.98±2.34 ) VS (18.63±2.15);RVHI%:(39.47±4.02)、(41.02±0.93)VS(36.21±4.27);WA%:(62.97±6.58)、(65.27±5.45)VS (58.23±4.08) ;WT%:(40.91±5.24)、(41.91±5.16)VS(38.06±4.15);P均0.05]。ADMSC治疗后2W与ADMSC治疗后3W相比,治疗组大鼠的MPAP、RVHI%、WA%和WT%没有统计学意义[MPAP(mmHg):(23.07±2.84)VS(22.98±2.34);RVHI%:(39.47±4.02)VS(41.02±0.93);WA%:(62.97±6.58)VS(65.27±5.45);WT%:(40.91±5.24)VS(41.91±5.16);P均0.05]。 (4)荧光显微镜观察到GFP标记的ADMSC在肺内的定植。 结论:ADMSC可以有效地降低野百合碱诱发的肺动脉高压大鼠的肺动脉压力,减轻右心室肥厚,改善肺小动脉的重构;ADMSC治疗1W时,仅是延缓MCT诱导的肺动脉高压的进展,而ADMSC治疗2W后,其治疗作用达到稳定的水平。
[Abstract]:Objective:
Objective To investigate the effects of adipose-derived mesenchymal stem cells (ADMSC) transplantation on pulmonary vascular remodeling in rats with monocrotaline-induced pulmonary hypertension.
Method:
90 Sprague-Dawley male rats were randomly divided into three groups: normal control group (Ctr), pulmonary hypertension group (PAH), adipose-derived mesenchymal stem cell treatment group (ADMSC), PAH group and ADMSC group. The same volume of normal saline was injected intraperitoneally in the Ctr group. The ADMSC group was given 10-6/1ml once through the left external jugular vein two weeks later. The Ctr group and PAH group were given 1 ml of normal saline once through the left external jugular vein. The index [RVHI% = RV weight / LV + S weight] was used to analyze lung tissue slices. The percentage of pulmonary arterial wall thickness (WT) to arterial diameter (ED) and the percentage of wall area (WA) to total vascular area (WA%) were measured by fluorescence microscopy. Observe the colonization of ADMSC labeled with GFP in the lung.
Result:
(1) The MPAP and RVHI% of PAH and RVHIin PAH group were significantly higher than those of Ctr group [MPAP (mmHg): (24.53 ((24.53 ((2.90) VS (14.81 ((14.81 ((24.53 (2.90) VS (14.81 (1.95), (33.18 (2.30) VS (15.08 (15.08 (15.08 (15.08 (15.35), (36.38 (3.28) VS (15.65 (15.65 (2.27); RVHIV%: (41.01 (1.01 (1.29) VS (24.29) VS (28.29) 28 VS (28.71 +2.08), (50.5) After ADMSC treatment, MPAP (mmHg) was (18.63 ((mmHg): (18.63 ((2.15) VS (24.53 ((24.53 (2.90), (23.07 ((2.84) VS (33.18 (2.30), (22.98 (2.34) VS (36.38 (3.38 (3.28); (22.38 (3.28); (22.98 (2.38 (3.28); (36.21 ((36.21 (4.27) VS (41.01 (41.01 (41.01), (41.01 (1 1 1.01 (24.01 (24.01 (24.29 48.75 (+ 2.13), 41.02 (+ 0.93) VS (50.52 (+ 1.49), P 0.05.
(2) After ADMSC treatment, 1 W, 2, 2, 2, 3 W, three time points, at each time point, the WA% and WT% of PAH group rats were significantly higher than those of Ctr group [WA%: (68.70 ((68.70 (3.43) VS (50.27 [(50.27 [(50.27 [(50.92)%, (50.27 [(50.27 [80.47 [(68.70 [(68.70 (3.43) 43) VS (50.27 (50.27 [80.47 [80.48 [6.19] 6.19) VS (51.61 [80.48 [6.48 [6.19] 19] VS (51.61 [52 + 3.19), (64.64 + 3.86) After treatment with ADMSC, both WA% and WT% were significantly lower than PAH group [WA%: (58.23 [(58.23 [(58.23 [(4.08) VS (68.70 [(68.70 [(68.70 [(68.70 [(68.70 [(68.43), (62.97 [(6.97 [6.58) VS (80.48 [(68.48 [6.19)], (65.27 [5.45] VS (84.01 [2.76; WT%: (38.06 [4.15] VS (46.09 [46.09 [46.70)], (40.09 [(40.91 [(40.91 [(24.24(41.91+5.16) VS (64.64+3.86), P 0.05.
(3) Compared with 1 W after ADMSC treatment, the MPAP, RVHI, WA%, WA% and WT% of the rats in the treatment group were significantly higher [MPAP (mmHg): (23.07 [(23.07 [(mmHg): (23.07 [(23.07 [(22.98 [(22.98 [2.34) VS (18.63 [(2.34) VS (18.63 [2.15)]; (18.47 [(39.47 [(4.02 [(41.02 [0.93 [0.93] VS (36.21 [(36.21 [(21.21.21.27.27]], (62.97 [65.97 [65.27 [65.27: (40.91 (+ 5.24)), (41.91 (+ 5.16) VS (38.06 (+ 4.15)) There was no significant difference in MPAP, RVHI, WA% and WT% between ADMSC treated rats and ADMSC treated rats at 2 W and 3 W [MPAP (mmHg): (23.07 [2.84] VS (22.98 [2.34]; RVHI% (39.47 [4.02] VS (41.02 [0.93]; WA% (62.97 [6.58] VS (65.27 [5.45]); WT% (40.91 [5.24] VS (41.41] VS (5.05]].
(4) the colonization of GFP labeled ADMSC in lung was observed under fluorescence microscope.
CONCLUSION: ADMSC can effectively reduce pulmonary artery pressure, relieve right ventricular hypertrophy and improve pulmonary artery remodeling in monocrotaline-induced pulmonary hypertension rats; ADMSC only delays the progress of MCT-induced pulmonary hypertension after 1 W treatment, and the therapeutic effect of ADMSC after 2 W treatment reaches a stable level.
【学位授予单位】：福建医科大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R329

【参考文献】

中国期刊全文数据库 前3条

1 林培森;谢筱露;谢良地;许昌声;;大鼠肺小动脉重构发生在肺动脉压增高之前[J];中华高血压杂志;2007年10期

2 马彩艳;陈君柱;;内皮祖细胞移植治疗儿童原发性肺动脉高压的初步探讨[J];浙江医学;2006年07期

3 孙波,刘文利;右心导管测定大鼠肺动脉压的实验方法[J];中国医学科学院学报;1984年06期

，

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