丹参酮ⅡA对子宫内膜异位症模型大鼠的治疗作用∗

摘要

目的：探讨丹参酮ⅡA 对子宫内膜异位症( EMS)大鼠的治疗作用及其机制。方法采用自体内膜移植法建立大鼠EMS模型,将建模成功的大鼠随机分为丹参酮ⅡA小、中、大剂量组,米非司酮组和模型对照组,每组10只。设10只正常大鼠为正常对照组,灌胃0.9％氯化钠溶液2 mL,模型对照组灌胃0.9％氯化钠溶液2 mL；米非司酮组灌胃米非司酮25 mg.kg－1.d－1；丹参酮ⅡA小、中、大剂量组腹腔注射丹参酮ⅡA10,20,30 mg.kg－1.d－1。灌胃4周后用游标卡尺检测移植物体积,光镜下观察异位内膜病理形态学的变化,Western blotting法检测子宫内膜Bcl-2、Bax、Caspase-9蛋白的表达。结果中、大剂量丹参酮ⅡA和米非司酮组大鼠子宫内膜异位组织的体积明显减少( P<0.05)。与模型对照组比较,丹参酮ⅡA小、中、大剂量组和米非司酮组异位子宫内膜移植物抑制率分别为17.81％,57.78％,58.88％,64.12％；中、大剂量丹参酮ⅡA和米非司酮组促使异位内膜呈萎缩性改变,并能抑制异位组织中Bcl-2蛋白的表达及促进Bax、Caspase-9蛋白的表达( P<0.05)。结论丹参酮ⅡA可显著抑制大鼠子宫内膜异位症移植物生长,其作用机制可能与通过减少抑凋亡蛋白Bcl-2表达,增加促凋亡蛋白Bax和凋亡相关蛋白Caspase-9蛋白的表达来调节细胞凋亡有关。%Objective To observe the effect of TanshinoneⅡA( TanⅡA) on endometriosis( EMS) rat model and study the possible mechanism. Methods EMS rat model was established by autologous endometrium transplantation. EMS rats were randomly divided into five groups: high-, medium-, low-dose TanⅡA group, mifepristone group and model control group( n=10), the other ten normal rats as normal control group.The rats in the model control group and normal control group were given 0.9% sodium chloride solution. The rats in the mifepristone group were given 25 mg . kg-1 . d-1 mifepristone. The rats in the high-, medium-, low-dose TanⅡA groups were given 30, 20 and 10 mg.kg-1.d-1 TanⅡA, respectively.Four weeks after the treatment, the volume of endometriotic implants in each rat was measured. Pathological changes of ectopic endometrium were observed under light microscope.Expression levels of Bcl-2, Bax and Caspase-9 in ectopic endomembrane of rats were determined by Western blotting. Results High and medium dose TanⅡA and mifepristone significantly reduced the volume of ectopic lesions(P<0.05).As compared with model control group, the inhibition rate of the ectopic lesions in low-, medium-, high-dose TanⅡA groups and mifepristone group was 17.81%, 57.78%, 58.88% and 64.12%, respectively.High and medium dose TanⅡA and mifepristone promoted atrophy of ectopic endometrium, inhibited the expression of Bcl-2 protein and promoted the expression of Bax and Caspase-9 in ectopic tissues( P<0.05) . Conclusion TanⅡA significantly decreases the size of ectopic lesions in rats, possibly through reducing the expression of Bcl-2 and increasing the expression of Bax and Caspase-9 to regulate cell apoptosis.