【作者】 王若光；

【导师】 尤昭玲；

【作者基本信息】 湖南中医学院 ， 中医诊断学， 2003， 博士

【摘要】 目的：从滋养细胞侵入，胎盘蜕膜血管网络形成、妊娠免疫监视／耐受机制、滋养细胞凋亡等角度，研究探讨黄芪、丹参复方成分提高胎盘血供的分子机制； 方法：分离提取黄芪，丹参有效组分(黄芪总皂甙、总黄酮；丹参提取丹参酮、丹参醌、丹参酸三部分)。一氧化氮合成酶(NOS)阻滞剂L-精氨酸甲酯(L-NANE)妊娠大鼠腹腔给药，制作一氧化氮(NO)合成阻滞模型(子宫-胎盘-胎儿缺血缺氧或妊娠高血压模型)，妊娠第12、18天剖腹取胎、胎盘／子宫，妊娠期测基础血压，每日测血压、蛋白质量、基本生理活动；电镜观察胎盘／蜕膜超微形态结构，并进行细胞凋亡计数；免疫组化(SABC法)检测胎盘滋养细胞bcl-2、Bax表达强度；原位杂交法检测胎盘滋养细胞、血管内皮细胞VEGF(血管内皮生长因子)、eNOS(内皮型一氧化氮合酶)、iNOS(诱导型一氧化氮合酶)、MCP-1(单核细胞趋化蛋白)、MMP9(基质金属蛋白酶9)mRNA表达。 结果：模型大鼠胎盘绒毛与空白组、治疗组比较明显减少，滋养细胞凋亡明显高于治疗组和空白组(p＜0.01)，胎盘病理损伤程度治疗组、空白组明显优于模型组；胎盘滋养细胞bcl-2、Bax表达黄芪丹参中药治疗组和空白组与模型组比较有明显差异(p＜0.01)；治疗组和空白组、阳性组胎盘滋养细胞VEGF mRNA(妊娠12d剖腹取胎)、eNOS mRNA表达明显高于模型组(p＜0.01)；胎盘滋养细胞MCP-1 mRNA、iNOS mRNA、MMP9 mRNA表达模型组明显高于治疗组和空白组，阳性组(p＜0.01)。 结论：黄芪、丹参复方成分阻抑一氧化氮合成阻滞大鼠胎盘免疫病理湖南中医学院博士学位论文王若光损伤，阻抑胎盘滋养细胞凋亡，并可能是通过调节bcl一2忍ax表达变化而影响细胞调亡。黄茂丹参复方成分促进胎盘部位血管生成和循环建立与维持，对提高胎盘血供具有重要作用。并通过抑制胎盘部位的免疫反应，改善胎盘及子宫螺旋小动脉病理损伤，防止胎盘后出血，提高胎盘滋养细胞活力和绒毛生成等。黄茂丹参复方成分通过上述途径达到提高胎盘血液供应、阻抑胎盘病理损伤，防治妊振高血压综合征、胎儿宫内生长迟缓等妊振并发症的目的。更多还原

【Abstract】 Objective: TO explore the molecular mechanism of the components of milkvitch-red sage compound elevating placenta blood supply from the point of view of invading by nutrient cells languishment, formation of placental decidual vas net, endurance mechanism and languishment of nutrient cells.Methods: Separate and abstract the effective components of Huangqi (Omni-SaponuK total-flavone) and Danshen( Danshen-ketone, Danshen-Quinone).Applying L-Arginine methyl ester (L-NAME) to pregnant rats by IP to make Nitrogen Oxide Synthesis blocking models (uterus-placenta-fetus lacking blood and oxygen model or pregnant hypertension syndrome model). On day 12,18 of pregnancy paunched the rats and took out the fetus and placenta/uterus. Measured the basal BP during pregnant period and BP, protein, basal activity each day. Observed placenta/ deciduas ultramicroscopic structure by electron microscope and took count oflanguishment cells. Measured the expressive intensity of bcl-2, Bax of placenta! nutrient cells by SABC method. Checked up the mRNA expression of VEGF> eNOS^ iNOS, MCP-K MMP9 of placental nutrient cells and vas endothelioid cells by FISFLResults: The placental villus of model group were obvious less, languishment of nutrient cells was obvious higher than the other groups(P<0.01).The pathologic damnification of treat group and blank group were superior to the model group.(p<0.01).The expressing of placental nutrient cells bcl-2, Bax of treat group and blank group were significant difference from model group(p<0.01).The mRNA expressing of placental nutrient cells VEGA, eNOS of treat group, blank group and positive group were obvious higher than model group(p<0.01),while MCP-1 > iNOS^ MMP9 were obvious lower than model group(p<0.01).Conclusion: The components of milkvitch-red sage compound restrain the placental immune pathologic damnification and the languishment of nutrient cells of NO Synthesis blocking rats, which is probably due to the accommodation of bcl-2/Bax expression. The components of milkvitch-red sage compound have an effect on elevating placenta blood supply by accelerating the form of placental vas and the establishment of circulation. It can also improve pathologic damnification of placenta and uterine helical artery, elevate vigor of placental nutrient cells and the formation of villus by restraining the immune reaction of placenta. From the approaches above, the components ofmilkvitch-red sage compound can elevate placenta blood supply and restrain the placental immune pathologic damnification to Prevent pregnant compounds such as PHS, IUGR and so on.更多还原