胶原蛋白对去势SD大鼠萎缩阴道上皮作用探讨

Therapeutic effect of collagen on vaginal atrophy in ovariectomized rats

目的观察胶原蛋白对阴道萎缩(vagina atrophy,VA)的治疗作用。方法采用去势法建立大鼠VA模型,40只大鼠采用随机数字表法分为假手术组、实验组(模型组10只,胶原蛋白组10只,雌激素10只)。去势术后第4周胶原蛋白组和雌激素组连续阴道给药14 d。测定大鼠体质量、pH值变化,免疫组化检测PCNA、MMP-1、TIMP-1、COL-Ⅰ、COL-Ⅲ、TGF-β1的表达水平,qPCR法检测MMP-1、TIMP-1、COL-Ⅰ、COL-Ⅲ、TGF-β1的mRNA表达,Western blot检测TGF-β1、Smad2/3、p-Smad2/3蛋白表达。结果经胶原蛋白治疗后,去势大鼠阴道pH值降低;上皮厚度增加,增殖能力增强;细胞外基质成分合成增多,降解减少;阴道组织中的磷酸化Smad2/3蛋白表达增高。相比于雌激素治疗组,胶原蛋白组大鼠子宫安全性更高。结论胶原蛋白可以有效缓解阴道萎缩,增加阴道组织中细胞外基质成分,促进阴道上皮的修复。

Objective To evaluate the therapeutic effect of collagen on vaginal atrophy(VA)in ovariectomized rats.Methods Forty female SD rats were randomized into sham-operated group,VA model group,collagen group and estrogen group(n=10).In the latter 3 groups,rat models of VA were established by ovariectomy and treated with collagen or estrogen for 14 consecutive days starting from the 4 th week after the operation.Body weight and vaginal pH ualue of the rats were measured daily,and the vaginal tissues were sampled after the treatments to examine the expression levels of PCNA,MMP-1,TIMP-1,COL-Ⅰ,COL-Ⅲand TGF-β1 using immunohistochemistry;the mRNA expression levels of MMP-1,TIMP-1,COL-Ⅰ,COL-Ⅲ,and TGF-β1 were detected using real-time PCR.Western blotting was used to detect the protein levels of TGF-β1,Smad2/3 and p-Smad2/3 in the vaginal tissues.Results The vaginal pH ualue of the ovariectomized rats decreased obviously after collagen treatment,which significantly increased the thickness and proliferative activity of the vaginal epithelium,enhanced the synthesis and lowered the degradation of extracellular matrix components,and obviously increased the expression of phosphorylated Smad2/3 protein in the vaginal tissues.Compared with estrogen treatment,collagen showed less adverse effects on the uterus.Conclusion Collagen can effectively alleviate vaginal atrophy,increase extracellular matrix components in the vaginal tissue and promote the repair of vaginal epithelium in ovariectomized rats.