沙利度胺联合孕三烯酮对大鼠子宫内膜异位症血管生成的影响  

Effects of thalidomide combined with gestrinone on angiogenesis in a rat endometriosis model

作　　者：马芳[1] 段彩芳 黄学惠[1] 高进华 敬晓涛[1] 杜娟[1] 

机构地区：[1]昆明医学院第一附属医院妇产科,云南昆明650032 [2]兴庆区月牙湖乡卫生院妇产科,宁夏银川756100 [3]海原县妇幼保健院儿科,宁夏中卫755200

出　　处：《中国新药与临床杂志》2010年第2期134-138,共5页Chinese Journal of New Drugs and Clinical Remedies

基　　金：昆明医学院研究生创新基金(KM2008L45)

摘　　要：目的探讨沙利度胺、孕三烯酮及两者联合用药对大鼠子宫内膜异位组织中血管生成的影响。方法24只子宫内膜异位症模型SD大鼠,随机分为模型对照、沙利度胺(20mg·kg-1·d-1)、孕三烯酮(0.5mg·kg-1·d-1)及联合用药(沙利度胺20mg·kg-1·d-1和孕三烯酮0.5mg·kg-1·d-1)4组,每组6只。药物溶于生理盐水中腹腔注射给药,模型对照组每日腹腔注射生理盐水2mL。给药4wk后处死,免疫组织化学SP法测定血管内皮生长因子(VEGF)和肿瘤坏死因子α(TNF-α)在异位内膜的表达,并通过Ⅷ因子标记异位子宫内膜血管,检测异位内膜组织中微血管密度(MVD)。结果沙利度胺组、孕三烯酮组及联合用药组异位内膜MVD、VEGF和TNF-α的表达均显著低于模型对照组(P<0.01),其中联合用药组MVD和VEGF比沙利度胺组和孕三烯酮组降低得更为显著(P<0.05),联合用药组TNF-α与孕三烯酮组无显著差异(P>0.05)。结论沙利度胺和孕三烯酮可抑制大鼠异位内膜的MVD、VEGF和TNF-α的表达,从而抑制子宫内膜异位症血管生成,当两者联合用药时,作用更强。AIM To investigate the effects of thalidomide and gestrinone on angiogenesis of endometriosis （EMs） model rats. METHODS Twenty-four SD rats of EMs model were divided randomly into 4 groups： model control, thalidomide （20 mg·kg-1·d-1）, gestrinone （0.5 mg·kg-1·d-1）, and combination （thalidomide 20mg·kg-1·d-1 and gestrinone 0.5mg·kg-1·d-1） group. Drugs were dissolved in normal saline and administrated by ip. Model control group was given normal saline 2 mL for each rat. After the 4-week administration, rats were killed and vascular endothelial growth factor （VEGF） and tumour necrosis factor-α（TNF-α） in ectopic endometrium were detected by immunohistochemical streptavidin-perosidase technique, and micro-vessel density （MVD） was determined by immunostaining for factor ⅧAg antibody. RESULTS The MVD and the expression of VEGF and TNF-α in thalidomide, gestrinone, and combination group were significantly lower than that of model control group （P 〈 0.01 ）, and MVD and expression of VEGF in combination group decreased significantly than that of thalidomide group and gestrinone group （P 〈 0.05） , while the expression of TNF-α showed no difference between the gestrinone group and the combination group （P 〉 0.05）. CONCLUSION Thalidomide and gestrinone inhibit MVD and the expressions of VEGF and TNF-α in rat ectopie endometrium so as to play an antiangiogenic effect in rat EMs. Thalidomide in combination with gestrinone can enhance the inhibitory effect on angiogenesis of EMs model rats.

关 键 词：子宫内膜异位症 沙利度胺 孕三烯酮 大鼠 血管内皮生长因子类 肿瘤坏死因子Α 微血 管密度 

分 类 号：R971.3[医药卫生—药品] R711.71[医药卫生—药学]