过氧化物酶体增殖物激活受体对人绒毛膜前列腺素代谢酶的调节

Regulation of human chorionic prostaglandin metabolizing enzymes by peroxisome proliferator-activated receptors

目的 探索不同妊娠状态人绒毛膜上过氧化物酶体增殖物激活受体(PPARs)各亚型的基因和蛋白表达差异及其与前列腺素代谢酶15-羟基前列腺素脱氢酶(PGDH)蛋白表达的相关性,进一步浅探PPARs对PGDH可能的调节机制和在分娩启动中可能发挥的作用。方法 收集2019年1月至12月正常足月妊娠未临产择期剖宫产分娩(TNL)、足月妊娠自然临产分娩(TL)的绒毛膜组织各40份,早产临产组(PL)22份,免疫组织化学实现PPARs和PGDH在绒毛膜滋养细胞内的定位,用RT-PCR和Western blot方法检测PPARs的mRNA及蛋白表达,检测同一份样本上PGDH的mRNA和蛋白表达,并统计PPAR各亚型蛋白表达与PGDH蛋白表达的相关性;收集足月妊娠顺产的绒毛膜组织,行绒毛膜滋养细胞培养,给予不同浓度PPARγ的特异性激动剂罗格列酮和拮抗剂GW9662处理细胞,检测PGDH的mRNA和蛋白表达。结果 PPARs和PGDH均在人绒毛膜组织上滋养细胞核表达。TL组PPARγmRNA和蛋白表达均低于TNL组(P<0.05),而两组PPARα、PPARβ的mRNA和蛋白表达差异无统计学意义(P>0.05)。PL组PPARγmRNA和蛋白表达均低于TL组(P<0.01);人绒毛膜组织上PPARγ的蛋白表达与PGDH的蛋白表达呈正相关;在离体细胞培养上罗格列酮可剂量依赖性上调PGDH蛋白和mRNA表达,GW9662则可抑制PGDH蛋白和mRNA表达,且表现为剂量依耐性。结论 绒毛膜上PPARγ的表达可能影响绒毛膜局部的前列腺素浓度,PPARγ临产前后的变化可能与分娩启动相关。

Objective To explore the differences in gene and protein expression of various subtypes of human chorionic per-oxisome proliferator activating receptors(PPARs)in different pregnancy states and their correlation withthe proteinexpressionof prosta-glandin metabolizing enzyme 15-hydroxyprostaglandin dehydrogenase(PGDH),and further explore the possible regulatory mechanism of PPARs on PGDH and the possible role of PPARS in the initiation of labor.Methods From January to December 2019,40 chori-onic tissues were collected from TNL and TL of normal full-term pregnancy,and 22 from PL group.Immunohistochemistryrealized the localization of PPARs and PGDH in chorionic trophoblast.The mR-NA and protein expression of PPARs were detected by RT PCR and Western blot,and it was detectedthe mRNA and protein expression of PGDH in the same sample,andcountthe correlation between the pro-tein expression of each subtype of PPAR and the protein expression of PGDH.Chorionic tissues of full-term pregnancy were collected and cultured in chorionic trophoblast cells.The cells were treated with rosiglitazone,a specific agonist of PPARγ,and GW9662,an antagonist,to detect the mRNA and protein expression of PGDH.Results Both PPARs and PGDH are expressed in the trophotrophic nucleus of human chorionic tissue.The mRNA and protein ex-pressions of PPARγin TL group were lower than those in TNL group(P<0.05),while the mRNA and protein expressions of PPARαand PPARβbetween two groups were not statistically significant(P>0.05).The mRNA and protein expressions of PPARγin PL group were lower than those in TL group(P<0.01).The protein expression of PPARγin human chorionic tissue was positively corre-lated with that of PGDH.In vitro cell culture,rosiglitazone up-regulated PGDH protein and mRNA expression in a dose-dependent manner,while GW9662 inhibited PGDH protein and mRNA expression with dose-dependent tolerance.Conclusion The expression of PPARγin the chorionic membrane may affect the concentration of prostaglandin in the chorionic membrane,and the change of PPARγbefore and after labor may be related to labor initiation.