摘要
目的探讨脂质体介导内皮抑素(ES)基因治疗裸鼠人子宫内膜异位症(EMs)的疗效及不良反应。方法BALB/c雌性裸鼠40只,建立皮下EMs模型后将动物随机均分为4组(n=10):A组,病灶局部注射脂质体介导的pcDNA3.1(+)-hES 20μg;B组,肌内注射脂质体介导的pcDNA3.1(+)-hES 20μg;C组,病灶局部注射脂质体介导的pcDNA3.1(+)空质粒20μg;D组,病灶局部注射等量培养液。观察治疗21d后裸鼠皮下异位病灶生长情况,检测病灶内微血管密度(MVD)、血管内皮细胞生长因子(VEGF)蛋白及治疗后第3、7天时VEGF mRNA的表达情况,并计算治疗21d后内生殖器(子宫、卵巢)重量及与体重的比值。结果A、B、C、D组病灶生长倍增时间分别是7.49、7.02、6.67、6.15d;A、B组注射ES基因后病灶生长抑制率分别为90.51%、43.05%。治疗21d后,A组MVD值(32±10/mm2)较B组(56±14/mm2)、C组(82±19/mm2)、D组(82±19/mm2)明显减少(P<0.05),后三组间差异无统计学意义,四组间VEGF表达水平差异无统计学意义(P>0.05)。与C、D组比较,A组在治疗第3天VEGF mRNA明显下降,第7天显著回升,而B组变化不明显。A、B组的内生殖器与体重比值(分别为0.008 6±0.002 5、0.008 0±0.003 4)较C、D组(分别为0.011 6±0.014 0、0.012 0±0.023 0)明显下降(P<0.05)。结论20μg脂质体介导pcDNA3.1(+)-hES治疗裸鼠人EMs有效,但须注意其对子宫、卵巢的影响。
Objective To investigate the effect of lipofectamine-mediated endostatin gene therapy on human endometriosis lesions in nude mice. Methods Nude mice used in the present study were divided into four groups （10 each） ： group A （treated with pcDNA 3. 1 （＋）-hES 20μg by injection into the lesion）, group B （treated with pcDNA 3. 1（＋）-hES 20μg by intramuscular injection）, group C （treated with pcDNA 3. 1（＋） 20μg by injection into the lesion） and group D （treated with the same amount of DMEM into the lesion）. Development of endometriosis was observed, microvascular density （MVD） and vascular endothelial factor （VEGF） levels in the four groups were compared 21 days after treatment, and VEGF mRNA level was assessed 3 days and 7 days after treatment. Side effect was evaluated by measuring the proportion by weight of internal reproductive organ （uterus and ovary） to body mass in each group. Results The multiplication time of endometriosis lesions in the four groups were 7. 49 days, 7.02 days, 6. 67 days and 6. 15 days, respectively. Inhibition ratio in group A was 90. 51%, and 43. 05% in group B. Twenty one days after treatment, MVD of lesion was obviously lower in group A （32± 10/mm^2） compared with that of group B （56±14/mm^2）, group C （72±12/mm^2） and group D （82±19/mm^2 ,ail P（ 0. 05）, while no significant difference existed between the two latter groups （P〉0. 05）. No obvious difference was found in VEGF value among the four groups 21days after treatment. Compared with groups C and D, VEGF mRNA level decreased on the 3rd day and increased on the 7th day after treatment in group A, but no change was found in group B. The proportion by weight of internal reproductive organ to body mass was lower in group A （0. 008 6±0. 002 5） and group B （0. 008 0±0. 003 4） than in group C （0. 011 6±0. 014 0） and group D （0. 012 0±0. 023 0, P〈0. 05）. Conclusions 20μg pcDNA 3. 1 （＋）-hES gene transference is effective for the treatment of human endometriosis in nude mice.
出处
《解放军医学杂志》
CAS
CSCD
北大核心
2009年第12期1430-1433,共4页
Medical Journal of Chinese People's Liberation Army
基金
国家自然科学基金资助项目(30672222)
广东省自然科学基金资助项目(8151008901000124
04009377)
广东省科技计划资助项目(2006B50107001
2007B080701011
2005B34201020)
广东省医学科研基金资助项目(A2009672)
