子宫主韧带Elastin/LOX/Elafin表达与盆腔器官膨出关系的研究
摘要
【目的】检测女性盆腔器官膨出(pelvic organ prolapse,POP)患者子宫主韧带中弹性蛋白(Elastin)、赖氨酰氧化酶(lysyl oxidase,LOX)和弹性蛋白酶抑制剂(Elafin)表达,探讨三种基因mRNA及蛋白表达变化与POP发生发展的关系。
【方法】选择2005年9月至2007年3月山东大学齐鲁医院妇产科收治的因子宫脱垂而行全子宫切除术患者60例为POP组,同期选择因妇科良性疾病、无压力性尿失禁(stress urinary incontinence,SUI)或POP而行全子宫切除术患者60例作为对照,所有入选者无肺气肿,烟雾病等弹性纤维异常疾病,近3个月内均未服用雌激素类药物,绝经前患者子宫内膜均处于增殖期。于手术中取子宫主韧带,采用逆转录-聚合酶链式反应(RT-PCR)法测定Elastin、LOX和Elafin mRNA的表达,免疫蛋白印迹法(Western blotting)检测三种蛋白的表达。各组结果之间进行独立样本t检验和双变量直线相关分析。
【结果】(1)无论绝经与否,POP组子宫主韧带Elastin mRNA及蛋白的表达均低于相应对照组,差异有统计学意义(P＜0.05);POP组中,绝经后患者子宫主韧带Elastin mRNA及蛋白表达较绝经前明显降低,差异有统计学意义(P＜0.05);(2)与Elastin整体变化趋势相同,无论绝经与否,POP组子宫主韧带LOX mRNA及蛋白的表达均低于相应对照组,差异有统计学意义(P＜0.05);POP组中,绝经后患者子宫主韧带LOX mRNA及蛋白表达较绝经前明显降低,差异有统计学意义(P＜0.05);(3)Elafin mRNA的表达,无论绝经与否,POP患者子宫主韧带中表达均较相应对照组增高,差异有统计学意义(P＜0.05);而POP组中Elafin mRNA的表达绝经前后无明显差异(P＞0.05):Elafin蛋白在对照组患者子宫主韧带中很少表达或几乎不表达,而POP组表达明显增高,POP组患者绝经前后其表达无明显差异(P＞0.05)。(4)相关分析显示,子宫主韧带Elastin mRNA及蛋白与LOX mRNA及蛋白整体变化趋势相同,两者的表达水平呈明显的直线正相关(P＜0.05),与Elafin mRNA及蛋白表达无直线相关关系(P＞0.05)。
【结论】(1)子宫主韧带Elastin表达减弱影响弹性纤维形成,导致其弹性机能减退,促进POP的发生:(2)子宫主韧带LOX mRNA及蛋白表达减弱使其对胶原/弹性蛋白分子内部及两种分子间交联作用减弱,其表达量可能受体内低雌激素水平的影响,无法形成稳定的胶原/弹性纤维,导致机械强度改变,从而易于断裂分解,或胶原/弹性纤维对蛋白酶水解作用的敏感性增高,导致对盆底器官支持作用减弱,促进POP及SUI的发生。(3)Elafin为一种弹性蛋白酶抑制剂,可以保护弹性蛋白免受水解,然而表达过多会使被锚定的老化弹性蛋白不能被及时分解,从而导致子宫主韧带等盆底结缔组织弹性功能减退,这可能是导致POP发生的原因之一。
[Objective] To investigate the Elastin, lysyl oxidase (LOX) and Elafinexpression in cardinal ligament of women with pelvic organ prolapse (POP) so as to determine the alteration that contributes to POP.
[Methods] The cardinal ligament samples were obtained from 60 POPsubjects and 60 non-POP control women underwent hysterectomy. Women with a history of connective tissue disorders were excluded. We selected only tissue samples from participants in the proliferative phase of menses for this study. Menstrual phase was confirmed by endometrial histology. Reverse transcription polymerase chain reaction (RT-PCR) was used to verify the mRNA level of Elastin, LOX and Elafin. The protein concentration of the three genes was determined by Western blotting technique, electrophoretic separation and quantification.
[ Results ] In all patiens, the POP group demonstrated a significant decreaseof expressions of Elastin and LOX in cardinal ligament than control group (P<0.05). There was an identical tendency in protein level of these two genes (P<0.05). In the POP group, the expressions of Elastin and LOX was significantly lower in postmenopausal patients than premenopausal patients(P<0.05). Inversely, the POP group demonstrated increase expression of Elafin than control group both in premenopausal and postmenopausal group (P<0.05). There was no significantly difference in the expression of Elafin between premenopausal POP group and postmenopausal group (P>0.05). There was a positive correlation between Elastin and LOX expressions in the two groups (P<0.05), but there was no correlation between Elastin and Elafin expressions (P>0.05).
[Conclusions] The present results suggest that, in POP patients, thedecrease expressions of Elastin and LOX in the cardinal ligaments may influence the formation of elastic fiber, destroy the metabolism and cross-linking of collagen and elastin, the increase expression of Elafin may interference the decomposition of aged elastin, all of these can reduce the stability of connective tissue of pelvic floor which leads to the development of POP. In addition, the low expression of estrogen in postmenopausal women may indirectly contribute to this process through influenceing the expression of LOX.
【方法】选择2005年9月至2007年3月山东大学齐鲁医院妇产科收治的因子宫脱垂而行全子宫切除术患者60例为POP组,同期选择因妇科良性疾病、无压力性尿失禁(stress urinary incontinence,SUI)或POP而行全子宫切除术患者60例作为对照,所有入选者无肺气肿,烟雾病等弹性纤维异常疾病,近3个月内均未服用雌激素类药物,绝经前患者子宫内膜均处于增殖期。于手术中取子宫主韧带,采用逆转录-聚合酶链式反应(RT-PCR)法测定Elastin、LOX和Elafin mRNA的表达,免疫蛋白印迹法(Western blotting)检测三种蛋白的表达。各组结果之间进行独立样本t检验和双变量直线相关分析。
【结果】(1)无论绝经与否,POP组子宫主韧带Elastin mRNA及蛋白的表达均低于相应对照组,差异有统计学意义(P＜0.05);POP组中,绝经后患者子宫主韧带Elastin mRNA及蛋白表达较绝经前明显降低,差异有统计学意义(P＜0.05);(2)与Elastin整体变化趋势相同,无论绝经与否,POP组子宫主韧带LOX mRNA及蛋白的表达均低于相应对照组,差异有统计学意义(P＜0.05);POP组中,绝经后患者子宫主韧带LOX mRNA及蛋白表达较绝经前明显降低,差异有统计学意义(P＜0.05);(3)Elafin mRNA的表达,无论绝经与否,POP患者子宫主韧带中表达均较相应对照组增高,差异有统计学意义(P＜0.05);而POP组中Elafin mRNA的表达绝经前后无明显差异(P＞0.05):Elafin蛋白在对照组患者子宫主韧带中很少表达或几乎不表达,而POP组表达明显增高,POP组患者绝经前后其表达无明显差异(P＞0.05)。(4)相关分析显示,子宫主韧带Elastin mRNA及蛋白与LOX mRNA及蛋白整体变化趋势相同,两者的表达水平呈明显的直线正相关(P＜0.05),与Elafin mRNA及蛋白表达无直线相关关系(P＞0.05)。
【结论】(1)子宫主韧带Elastin表达减弱影响弹性纤维形成,导致其弹性机能减退,促进POP的发生:(2)子宫主韧带LOX mRNA及蛋白表达减弱使其对胶原/弹性蛋白分子内部及两种分子间交联作用减弱,其表达量可能受体内低雌激素水平的影响,无法形成稳定的胶原/弹性纤维,导致机械强度改变,从而易于断裂分解,或胶原/弹性纤维对蛋白酶水解作用的敏感性增高,导致对盆底器官支持作用减弱,促进POP及SUI的发生。(3)Elafin为一种弹性蛋白酶抑制剂,可以保护弹性蛋白免受水解,然而表达过多会使被锚定的老化弹性蛋白不能被及时分解,从而导致子宫主韧带等盆底结缔组织弹性功能减退,这可能是导致POP发生的原因之一。
[Objective] To investigate the Elastin, lysyl oxidase (LOX) and Elafinexpression in cardinal ligament of women with pelvic organ prolapse (POP) so as to determine the alteration that contributes to POP.
[Methods] The cardinal ligament samples were obtained from 60 POPsubjects and 60 non-POP control women underwent hysterectomy. Women with a history of connective tissue disorders were excluded. We selected only tissue samples from participants in the proliferative phase of menses for this study. Menstrual phase was confirmed by endometrial histology. Reverse transcription polymerase chain reaction (RT-PCR) was used to verify the mRNA level of Elastin, LOX and Elafin. The protein concentration of the three genes was determined by Western blotting technique, electrophoretic separation and quantification.
[ Results ] In all patiens, the POP group demonstrated a significant decreaseof expressions of Elastin and LOX in cardinal ligament than control group (P<0.05). There was an identical tendency in protein level of these two genes (P<0.05). In the POP group, the expressions of Elastin and LOX was significantly lower in postmenopausal patients than premenopausal patients(P<0.05). Inversely, the POP group demonstrated increase expression of Elafin than control group both in premenopausal and postmenopausal group (P<0.05). There was no significantly difference in the expression of Elafin between premenopausal POP group and postmenopausal group (P>0.05). There was a positive correlation between Elastin and LOX expressions in the two groups (P<0.05), but there was no correlation between Elastin and Elafin expressions (P>0.05).
[Conclusions] The present results suggest that, in POP patients, thedecrease expressions of Elastin and LOX in the cardinal ligaments may influence the formation of elastic fiber, destroy the metabolism and cross-linking of collagen and elastin, the increase expression of Elafin may interference the decomposition of aged elastin, all of these can reduce the stability of connective tissue of pelvic floor which leads to the development of POP. In addition, the low expression of estrogen in postmenopausal women may indirectly contribute to this process through influenceing the expression of LOX.
引文
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