全反式维A酸对子宫肌瘤发生及iNOS表达的意义

Effect of ATRA on occurrence of uterine leiomyomas and iNOS expression in rats

目的初步探讨诱导细胞分化剂全反式维A酸(AT-RA)对雌孕激素诱导性子宫肌瘤的发生、发展的影响,以及对维A酸受体α(RARα)、诱导型一氧化氮合酶(iNOS)表达的影响。方法 60只♀Wistar大鼠随机分为5组,空白对照组(A组)、模型组(B组)、ATRA低剂量组(C组)、中剂量组(D组)、高剂量组(E组),采用雌、孕激素负荷法建立子宫肌瘤大鼠模型,测量并计算大鼠子宫湿重、子宫系数、子宫各径线数值,HE染色镜下观察大鼠子宫平滑肌病理改变,同时应用免疫组化染色检测大鼠子宫肌层组织内RARα、iNOS的表达情况。采用经典细胞诱导分化剂ATRA诱导细胞分化,观察对子宫肌瘤形态学上的改变及肌层中RARα、iNOS的表达的影响。结果大量雌孕激素冲击12周可制备理想的子宫肌瘤大鼠模型,模型组大鼠子宫湿重等各径线值均明显增加(P<0.01);大体观子宫色泽晦暗,明显肿胀、结节;镜下大鼠子宫平滑肌增生,细胞排列紊乱。模型组中RARα、iN-OS的表达均明显增高(P<0.05),ATRA治疗后iNOS的表达率明显下降(P<0.05)。结论高强度雌孕激素依赖可导致子宫肌瘤的发生;子宫肌瘤发生中NO明显诱生,且RARα的表达增加;诱导细胞分化能明显抑制子宫平滑肌细胞的增殖,这种抑制可能是通过与其受体RARα结合抑制NO诱生而产生的。

Aim To study the effect of all-transretinoic acid（ATRA）,a cell differentiation agent on the occurrence and growth of female progestogen-induced uterine fibroids, and the influence of ATRA on the expression of retinoic acid receptor-α（RARα） and inducible nitricoxide synthase（iNOS）.Methods 60 Wistar rats were randomly divided into 5 groups,control（A）,model group（B）,ATRA low-dose group（C）,ATRA mid-dose group（D） and ATRA highdose group（E）.Fibroid model of rat was established with Estrogen and Progesterone Load method.Uterus wet weight,uterus coefficient,length of left and right uterine horns,maximum diameter of uterine horns,uterus length,the upper and lower width of cervix were measured and calculated.General shape of rats′uterus was observed.Rats＇smooth muscle change was observed under HE dyeing observes chromatoscope.The expression of RARα and iNOS were detected by immunohistochemistry method.Classical cell differentiation agent ATRA was used to induce cell＇s differentiation and the morphological change in uterine fibroids and its effect on the expression of RARα and iNOS in muscular layer.Results Fibroid model of rat was established with the shock of estrogen and progesterone after 12 weeks.In model group,uterus wet weight and each diameter line value increased significantly（P0.01）,and the uterus looked tarnished and swelling with nodules.Smooth muscle proliferation was observed.The cell arrangement was disordered.Compared with control,model group′s expression of RARα and iNOS increased significantly（P0.05）.After the ATRA′s treatment,the expression of iNOS decreased remarkally（P0.05）.Conclusions High estrogen and progesterone-dependence results in the occurence of uterione fibroids.NO can be induced distinctly in uterine fibroids and the expression of RARα augments.Induction of cell differentiation can inhibit the proliferation of uterine smooth muscle cells.Which results from the inhibition of NO＇s induction through the combination of ATRA and its receptors.