【作者】 赵锐；

【导师】 马宝璋；

【作者基本信息】 黑龙江中医药大学 ， 中医妇科学， 2009， 博士

【摘要】 目的：探讨“补肾宁”对氢化可的松法复制肾阳虚模型大鼠，补肾促排卵的作用机制。方法：成年雌性SD大鼠60只，随机分为6组，每组10只。第1组为空白对照组，后5组建立动物模型，分别为模型对照组、克罗米芬组、补肾宁低、中、高剂量组。空白对照组每日肌注等容积生理盐水，其余5组，每日下肢肌注氢化可的松注射液36mg／kg，连续11天，制备肾阳虚模型大鼠。11天后按组别分别用药治疗，治疗期为15天。实验观察模型大鼠用药前后体重及血清E₂、P激素水平的变化；下丘脑、垂体、肾上腺、卵巢、子宫显微光镜下组织形态学的变化；垂体、肾上腺超显微结构的改变；下丘脑、子宫、卵巢ER的表达；下丘脑ERmRNA及卵巢MMP-9mRNA的表达，并进行组间的比较。结果：①补肾宁高、中剂量组能够提高模型大鼠用药前后的体重，明显优于与模型组、克罗米芬组，相较有显著性差异（P＜0．01），同时优于补肾宁低剂量组（P＜0．05）。②补肾宁各剂量组及克罗米芬组均能明显提高模型大鼠血清E₂、P水平，与模型对照组比较有显著性差异（P＜0．05），与空白对照组比较无显著性差异（P＞0．05），其中克罗米芬组及补肾宁高剂量组作用最为显著。③造模后大鼠垂体、肾上腺存在不同程度的损伤，补肾宁组可减轻损伤程度，剂量越高，效果越明显；模型对照组大鼠卵巢中生长卵泡及黄体数目明显减少，补肾宁剂量组及克罗米芬组能显著增加不同阶段卵泡及黄体数目，其中补肾宁高、中剂量组、克罗米芬组与空白对照组相类似；补肾宁高、中剂量组能够明显改善模型大鼠子宫间质和腺体的形态，接近正常对照组，优于克罗米芬组；各组间下丘脑光镜观察无显著性差异。④补肾宁能减轻模型大鼠垂体、肾上腺超微结构的损伤，其中高、中剂量组效果较为明显，优于克罗米芬组。⑤补肾宁组与克罗米芬组均能不同程度的增强下丘脑、卵巢、子宫的ER表达强度，其中补肾宁高、中剂量组作用显著，与模型对照组比较有显著性差异（P＜0．01），与空白对照组无显著性差异（P＞0．05），同于优于克罗米芬组（P＜0．05）。⑥补肾宁组与克罗米芬组均能增强下丘脑ERmRNA及卵巢MMP-9mRNA的表达强度，与模型对照组比较差异显著（P＜0．05），其中补肾宁高、中剂量组作用最为明显，与模型对照组比较有极显著性差异（P＜0．01），与空白对照组无显著性差异（P＞0．05），补肾宁高剂量组卵巢MMP-9mRNA的表达强度优于克罗米芬组（P＜0．05）。结论：补肾宁能够整体调节肾阳虚模型大鼠下丘脑—垂体—卵巢轴的机能。明显提高模型大鼠造模前后的体重及血清E₂、P水平；改善模型大鼠垂体、肾上腺、子宫及卵巢的光镜组织学形态及垂体、肾上腺超微结构；增强模型大鼠下丘脑、卵巢、子宫的ER水平的表达强度；增强模型大鼠下丘脑ERmRNA和MMP-9mRNA的表达强度。补肾宁能够促进卵泡的发育与排出，恢复卵巢的功能，整体作用优于克罗米芬。更多还原

【Abstract】 Objective:To observe the effect and mechanism which BuShenNing（BSN） decoction promoted the ovulation of kidney-yang defieiency femalerat model,which replicate by applying hydoreortisone.Methods:The sixty mature female Sprague-Dawley rats were dividedinto six groups radomly:normal contrast group,model contrast group,clomifene group,BSN low,middle and high dosage group.normal contrastgroup used physiological saline,the other groups replicated kidney-yangdefieiency model by muscle injecting hydoreortisone 36mg/kg,for 11day.After 11 day,used the corresponding medicine treatment by 15day.Observe each group the change of rat body weight;the level of serumestrogen（E₂） and progesterone（p）;each group the hypothalamus,pituitary,adrenal,ovarian,uterine changed in histomorphological differences by lightmicroscope;ultrastrucure changed of pituitary and adrenal;the expression ofhypothalam,usterine,ovarian estrogen receptor（ER）;the expression ofhypothalamus estrogen receptor mRNA（ERmRNA） and ovarian matrixmetalloproteinase-9 Mrna（MMP-9mRNA）Results:①After taken medicine,the weight of rat in BSN middle andhigh dosage group heighten evidently,have significant differerce comparedwith model contrast group and clomifene group（P＜0.01）,and superiord toBSNlow dosage group（P＜0.05）.②BSN low,middle and high dosage groupand clomifene group all increased level of the rat serum estrogen andprogesterone,significantly superiored to model contrast group（P＜0.05）,were similar to normal contrast group（P＞0.05）,clomifene group and BSNhigh dosage group the most significant.③BSN low,middle and high dosagegroup improvd the structure damage of pituitary and adrenal of deficientkidney yang rat,the higher the dose,the effect of the more obvious;modelcontrast group decreased in number of ovarian growth follicle and luteum,BSN low,middle,high dosage group and clomifene group could increase in quantity of ovarian growth follicle and luteum,BSN middle,high dosagegroup and clomifene group were similar to normal contrast group;BSNmiddle and high dosage group improved the morphology of rat uterinestromal and glandular,were superiored to clomifene group,were similar tonormal contrast group;hypothalamus of each group were observed nosignificant difference by light microscope.④BSN low,middle and highdosage group improvd ultrastrucure damage of pituitary and adrenal,BSNmiddle and high dosage group were superiored to clomifene group.⑤BSNlow,middle,high dosage group and clomifene group all could enhance theexpress of hypothalamus,uterine,ovarian ER,BSN middle and high dosagegroup were similar to normal contrast group（P＞0.05）,were superiored toclomifene group（P＜0.05） and model contrast group（P＜0.01）.⑥BSN low,middle,high dosage group and clomifene group all could enhance the expressof hypothalamus ERmRNA and ovarian MMP-9mRNA,were superiored tomodel contrast group（P＜0.05）,BSN middle and high dosage group weresignificant superiored to model contrast group（P＜0.01）,were similar tonormal contrastgroup（P＞0.05）,BSN high dosage group was superiored toclomifene group in the express of ovarian MMP-9mRNA（P＜0.05）Conclusions:BSN decoction could overall regulation hypothalamus-pituitary-ovarian axis function of kidney-yang defieiency female rat model.BSN decoction could significant improve the weight of rat,level of the ratserum estrogen and progesterone;improve the histomorphology of ratpituitary,adrenal,ovarian,uterine and ultrastrucure of pituitary and adrenal;enhance the express of hypothalamus,uterine,ovarian ER;enhance theexpress of hypothalamus ERmRNA and ovarian MMP-9mRNA.BSNdecoction had the effect of inducing ovulation and recovering the function ofovary,the allover effect was better than clomifene.更多还原