【摘要】 目的研究子痫前期患者胎盘滋养细胞基质金属蛋白酶(MMP)9、2及其组织抑制物(TIMP)1、2,肿瘤转移抑制基因KiSS-1 mRNA、蛋白的表达变化及其与子痫前期发病的关系。方法采用RT-PCR、免疫印迹(western blot)法对30例正常足月妊娠妇女(正常妊娠组)和10例妊娠期高血压患者(高血压组)及27例子痫前期(子痫前期组)患者胎盘滋养细胞中MMP-9、MMP-2、KiSS-1、TIMP-1和TIMP-2基因mRNA及蛋白表达水平[均以相对吸光度(A)表示]进行检测;应用明胶酶谱分析法,检测3组妇女胎盘孵育液MMP-9、MMP-2活性。结果(1)胎盘滋养细胞浸润相关基因mRNA表达水平:子痫前期组MMP-9、MMP-2 mRNA表达水平分别为0．39±0．05和0．71±0．16,均明显低于正常妊娠组的0．78±0．11和1．63±0．31,两组分别比较,差异有统计学意义(P均<0．05)。高血压组MMP-9 mRNA的表达水平明显高于重度子痫前期患者,差异有统计学意义(P<0．05)。子痫前期组胎盘滋养细胞KiSS-1 mRNA和TIMP-1 mRNA的表达水平分别为1．97±0．21和1．11±0．18,均明显高于正常妊娠组的0．69±0．27和0．65±0．19,差异均有统计学意义(P<0．05);高血压组胎盘滋养细胞KiSS-1 mRNA表达水平低于子痫前期组,但与正常妊娠组比较,差异无统计学意义(P>0．05)。重度子痫前期患者胎盘滋养细胞TIMP-2 mRNA表达水平明显高于正常妊娠组,差异均有统计学意义(P<0．05)。(2)胎盘滋养细胞浸润相关基因的蛋白表达水平:子痫前期组MMP-9、MMP-2基因的蛋白表达水平分别为1．07±0．35和0．74±0．23,均明显低于正常妊娠组的2．43±0．92和1．48±0．78,差异均有统计学意义(P<0．05)。子痫前期组胎盘KISS-1和TIMP-1蛋白表达水平分别为2．46±0．39和1．51±0．40,均明显高于正常妊娠组的0．91±0．35和0．93±0．56,差异均有统计学意义(P<0．05)。子痫前期组胎盘滋养细胞TIMP-2蛋白表达水平与正常妊娠组及高血压组比较,差异均无统计学意义(P>0．05)。(3)胎盘MMP-9和MMP-2酶比活性:子痫前期组分别为(2．67±0．53)和(1．13±0．28)灰度·g-1·L-1,均明显低于正常妊娠组的(8．44±3．70)和(3．87±1．43)灰度·g-1·L-1,差异均有统计学意义(P<0．05)。结论子痫前期患者胎盘滋养细胞促进浸润基因。MMP-9、MMP-2表达降低和抑制浸润基因KiSS-1和TIMP-1表达升高,可能在子痫前期胎盘缺血缺氧中起重要作用。更多还原

【Abstract】 Objective To study the mRNA and protein expression of matrix metalloproteinase (MMP)9, 2, metastasis suppressor gene KiSS-1, tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2 in placenta of preeclampsia patients and their relation to the pathogenesis of preeclampsia. Methods Expression of MMP-9,MMP-2, KiSS-1,TIMP-1,TIMP-2 mRNAs and proteins in placenta from 27 cases of preeclampsia, 10 cases of gestational hypertension and 30 cases of normal term pregnant women was detected by semi-quantitative RT-PCR, western blotting, and enzyme activity of MMP-9 and MMP-2 was measured by gelatin zymography. Results (1) Expression of MMP-9 and MMP-2 mRNA in placenta of preeclampsia (0. 39±0. 05 and 0. 71±0. 16) was significantly lower than that in normal term pregnancy (0. 78±0. 11 and 1.63±0.31, P<0.05). Expression of KiSS-1 and TTMP-1 mRNAs in placenta of preeclampsia (1.97±0. 21 and 1. 11±0. 18 ) was significantly higher than that in normal term pregnancy (0. 69±0. 27 and 0. 65±0. 19) (P < 0.05. ) . There was no significant difference in TIMP-2 mRNA level between preeclampsia and normal pregnancy ( P > 0. 05 ). (2) Expression of MMP-9 and MMP-2 proteins in preeclampsia (1. 07±0. 35 and 0. 74±0. 23) was significantly lower than that in normal term pregnancy (2. 43±0. 92 and 1. 48±0. 78) (P < 0. 05). Expression of KiSS-1 and TIMP-1 proteins in placenta of preeclampsia (2. 46±0. 39 and 1. 51±0. 40) was significantly higher than that in normal pregnancy (0. 91±0. 35 and 0. 93±0. 56) (P <0. 05). There was no significant difference in TIMP-2 protein level between preeclampsia and normal pregnancy (P>0. 05). (3)Enzyme activity of MMP-9 and MMP-2 in placenta of preeclampsia [(2. 67±0.53) gray level·g-1·L-1 and (1.13±0.28) gray level·g-1·L-1)] was significantly lower than that in placenta of normal pregnancy [ (8. 44±3. 70) gray level·g-1·L-1 and (3.87±1.43) gray level·g-1·L-1 ] (P <0. 05). Conclusion Abnormal expression of MMP-9,MMP-2, KiSS-1 and TIMP-1 can cause insufficiency invasion of trophoblast in preeclampsia and superficial placentation, which may play an important role in the pathogenesis and development of preeclampsia.更多还原