CTGF HGF及Cx 43在多囊卵巢综合征大鼠卵巢中的表达及二甲双胍的干预作用

Expression of and effects of metformin on connective tissue growth factor,hepatocyte growth factor and gap junction protein-43 in rats with polycystic ovary syndrome

目的观察结缔组织生长因子(CTGF)、肝细胞生长因子(HGF)、间隙连接蛋白43(Cx43)在多囊卵巢综合征(PCOS)大鼠卵巢中的表达,并探讨二甲双胍用于治疗PCOS的作用机制。方法选取6周龄清洁级雌性Wistar大鼠55只,分为对照组15只、模型组40只。应用来曲唑灌胃建立PCOS大鼠模型,模型组40只分取10只作为造模效果评价,余二甲双胍治疗组15只和PCOS组15只分别喂服二甲双胍和生理盐水。14d后麻醉大鼠并取材,光镜观察卵巢的情况,免疫组织化学法测定卵巢组织中CTGF、HGF、CX43的表达水平。结果 PCOS组卵巢颗粒细胞及卵泡膜细胞CTGF、HGF表达较对照组升高,Cx43的表达降低,而在干预组CTGF、HGF的表达比PCOS组均明显下降,Cx43的表达升高,差异均有统计学意义(P<0.05)。结论 CTGF、HGF、Cx43在PCOS大鼠的发病中起着重要作用,而二甲双胍可调节这3种因子在PCOS大鼠卵巢上的表达,从而起到治疗作用。

Objective To investigate the expression of ovarian connective tissue growth factor （CTGF）, hepato- cyte growth factor （HGF） and gap junction protein-43（Cx43） in rats with polycystic ovary syndrome （PCOS） and to de- termine the mechanisms of metformin on PCOS. Methods We randomly assigned 55 specific pathogen-free 6-week- old female Wistar mice to control group （n=15） and PCOS model group （n=40）, with the latter being established by administration of Letrozole. This was followed by further grouping for assessment of the PCOS model （n=10） and ad- ministration of metformin （metformin group, n=15） and sterile distilled water （control group, n=15）, respectively. At day 14 following intervention, all mice were anesthetized for tissue extraction to determine changes in the endometri- um as assessed by light microscopy and expression of CTGF, HGF and Cx-43 by immunohistochemical assay. Results Significantly higher levels of HGF and CTGF expression yet suppressed Cx43 were noted in granulosa and theca cells in POCS group （all P〈0.05）, but not in control group. When compared with POCS group, metformin treatment resulted in markedly attenuated CTGF and HGF yet increased Cx43 expression （all P〈0.05）. Conclusion Metformin treat- ment proves effective in rats with POCS via modulation of ovarian CTGF, HGF and Cx43 expression, the markers that play a crucial role in the pathogenesis of POCS.