CAJ | 학술논문

目的：探讨盆腔器官脱垂(POP)患者子宫旁韧带组织中基质金属蛋白酶-2(MMP-2)及基质金属蛋白酶组织抑制物-2(TIMP-2)与转化生长因子β1(TGF-β1)的表达及关系。方法选取2014年7~10月武汉大学人民医院妇产科收治的20例POPⅡ级及以上患者(POP组)和15例因妇科良性疾病行子宫全切术患者(对照组)的宫旁韧带(骶韧带、主韧带)为试验材料，采用Western blot和实时荧光定量PCR检测两组组织中TGF-β1、MMP-2、TIMP-2的蛋白和mRNA表达；比较两组TGF-β1、MMP-2、TIMP-2的表达差异，并从蛋白水平分析POP组TGF-β1与MMP-2、TIMP-2表达的相关性。结果 Western blot结果显示POP组TGF-β1、TIMP-2表达均降低，MMP-2表达升高，且与对照组相比差异有统计学意义(t=3.432，P=0.019；u=0.000，P=0.02；u=0.000，P=0.003)；同样的，实时荧光定量PCR中TGF-β1、TIMP-2表达降低，MMP-2表达上调，且与对照组相比差异有统计学意义(t=8.241，P=0.001；t=6.869，P=0.002；t=4.930，P=0.004)；相关性分析表明，TGF-β1与MMP-2表达呈负相关(r=-0.926，P=0.015)，而与TIMP-2表达呈正相关(r=0.886，P=0.046)。结论 POP患者宫旁韧带中TGF-β1表达的降低可能是通过上调MMP-2、下调TIMP-2导致细胞外基质降解增加，盆底支持组织弹性减弱，TGF-β1通路可以通过调节MMP-2和TIMP-2的平衡参与POP的发生。
목적：탐토분강기관탈수(POP)환자자궁방인대조직중기질금속단백매-2(MMP-2)급기질금속단백매조직억제물-2(TIMP-2)여전화생장인자β1(TGF-β1)적표체급관계。방법선취2014년7~10월무한대학인민의원부산과수치적20례POPⅡ급급이상환자(POP조)화15례인부과량성질병행자궁전절술환자(대조조)적궁방인대(저인대、주인대)위시험재료，채용Western blot화실시형광정량PCR검측량조조직중TGF-β1、MMP-2、TIMP-2적단백화mRNA표체；비교량조TGF-β1、MMP-2、TIMP-2적표체차이，병종단백수평분석POP조TGF-β1여MMP-2、TIMP-2표체적상관성。결과 Western blot결과현시POP조TGF-β1、TIMP-2표체균강저，MMP-2표체승고，차여대조조상비차이유통계학의의(t=3.432，P=0.019；u=0.000，P=0.02；u=0.000，P=0.003)；동양적，실시형광정량PCR중TGF-β1、TIMP-2표체강저，MMP-2표체상조，차여대조조상비차이유통계학의의(t=8.241，P=0.001；t=6.869，P=0.002；t=4.930，P=0.004)；상관성분석표명，TGF-β1여MMP-2표체정부상관(r=-0.926，P=0.015)，이여TIMP-2표체정정상관(r=0.886，P=0.046)。결론 POP환자궁방인대중TGF-β1표체적강저가능시통과상조MMP-2、하조TIMP-2도치세포외기질강해증가，분저지지조직탄성감약，TGF-β1통로가이통과조절MMP-2화TIMP-2적평형삼여POP적발생。
Objective To investigate the expression of matrix metalloproteinase-2 (MMP-2) and tissue inhibitors of metalloproteinase-2 (TIMP-2) in parametrial ligaments and their relationships with transforming growth factor-β1 (TGF-β1) of patients with pelvic organ prolapsed (POP). Methods A cohort of 20 POP patients (POP group)and 15 pa-tients who received hysterectomy for benign gynecological diseases (control group, 6 patients of cervical intraepithelial neoplasia and 9 patients of uterine fibroid) was accrued from July to October 2014 at Renmin Hospital of Wuhan Uni-versity. The expressions of TGF-β1, MMP-2 and TIMP-2 in parametrial ligaments were examined by Western Blot and Real-time Quantitative PCR respectively. The differences of expression in the two groups and correlational analyses were conducted between TGF-β1 and MMP-2 as well as TIMP-2. Results It was a significantly lower expression of TGF-β1 and TIMP-2 (t=3.432, P=0.019; u=0.000, P=0.02), but higher expressions of MMP-2 (u=0.000, P=0.003) at protein level as well as at mRNA level (t=8.241, P=0.001; t=6.869, P=0.002; t=4.930, P=0.004) in parame-trial ligaments from POP group compared to controls. Correlation analysis showed that TGF-β1 and TIMP-2 were positively correlated (r=0.886, P=0.046), while TGF-β1 and MMP-2 were negatively correlated (r=-0.926, P=0.015). Conclusion The expression of TGF-β1 is lower in parametrial ligaments from patients with POP that may up-regulate the expression of MMP-2 and down-regulate the expression of TIMP-2, resulting in the in-creased degradation extracellular matrix (ECM) and then relaxation of pelvic support tissue. TGF-β1 pathway can con-cerned in pathophysiology of POP by adjusting the balance of MMP-2 and TIPM-2.