【作者】 于源源；

【导师】 刘瑞芬；

【作者基本信息】 山东中医药大学 ， 中医妇科学， 2012， 博士

【摘要】 目的：评价中药综合疗法治疗血瘀肾虚证慢性盆腔炎的临床疗效，为其临床应用提供科学的依据。观察活血补肾综合疗法调控慢性盆腔炎模型大鼠血清血管内皮细胞功能及子宫组织中抗粘连相关指标的变化，探讨其机制，为临床应用提供实验室依据。方法：采用前瞻性、随机、开放、平行对照、多中心临床试验研究方法，共采集血瘀肾虚证慢性盆腔炎病例162例，分为两组：试验组79例，采用中药内服法+灌肠法+外敷法综合疗法；对照组83例，采用中药内服单一疗法。通过观察治疗前后临床症状、体征、实验室检查、生存质量的改善情况以评价临床疗效。以Wistar雌性中年大鼠为实验对象，采用睡眠剥夺+铃声惊吓+混合细菌+机械损伤方法，复制血瘀肾虚证慢性盆腔炎动物模型。将72只大鼠随机分为正常组、假手术组、模型组、中药内服高、中、低剂量组及综合治疗高、中、低剂量组。酶联免疫吸附测定法（ELISA）检测各组大鼠血清的血栓素B₂（TXB₂）、6-酮-前列腺素F1（6-keto-PGF1）、内皮素-1（ET-1）浓度；大鼠子宫形态学观察后，免疫组织化学法S-P法检测各组大鼠子宫组织成纤维细胞生长因-2（FGF-2）、胰岛素样生长因子-1（IGF-1）、基质金属蛋白酶-2（MMP-2）的表达。结果：临床研究慢性盆腔炎活血补肾综合疗法的综合疗效、中医证候、局部体征疗效愈显率，分别由44.87%提升为82.67%、由50%提升为81.33%，由44.87%提升为73.33%；中药综合疗法和中药单一口服疗法的疗效比较有显著性差异（P<0.01）。中医综合疗法较单一疗法能明显提高患者生理领域、心理领域、社会关系领域评分及总积分（P<0.01），显著改善患者生存质量，且具有安全性高、复发率低的优势。慢性盆腔炎模型大鼠血清中ET-1、TXB₂水平较正常组升高，6-keto-PGF1水平较正常组降低，大鼠子宫组织中的IGF-1、FGF-2、MMP-2的表达较正常组大鼠升高，差异有显著性（P<0.05）。治疗后，除中药内服低剂量组外，各治疗组大鼠血清中ET-1、TXB2的水平下降，6-keto-PGF1水平升高，大鼠子宫组织中MMP-2的表达升高（P<0.05或P<0.01）；各治疗组中大鼠子宫组织中IGF-1、FGF-2的表达较模型组降低，差异有极显著性（P<0.01），但未达正常水平。其中综合治疗高、中剂量组对模型大鼠血清中ET-1、TXB₂、6-keto-PGF1的水平及模型大鼠子宫组织中的IGF-1、FGF-2、MMP-2的表达优于其他治疗组。结论：活血补肾综合疗法治疗本病安全有效，值得临床推广使用。通过对慢性盆腔炎模型大鼠血管内皮细胞因子、抗粘连相关指标的调控，使机体血管扩张，改善循环状态，增加盆腔有效循环血流量，从而改善了盆腔缺血缺氧的瘀血状况，促进炎症的吸收以及萎缩腺体的恢复，松解盆腔粘连。更多还原

【Abstract】 Objective：To evaluate the clinic effect of chronic pelvic inflammatory disease(CPID)of blood stagnate and deficiency of the kidney treated by comprehensivetreatmen,and providing evidences for clinical scientific application.To explore themechanism of the treatment of promoting blood circulation and tonifying the kidneycomprehensive treatment on the rats with chronic pelvic inflammatory disease（CPID） byobserving the changes of endothelial function and antiadhesion.Methods：The subject used randomized，multi-center， blinded evaluation of testmethod,162cases of chronic pelvic inflammatory disease of blood stagnate and deficiencyof the kidney were divided into two groups randomly; treatment group had79cases that isPEN QIANG YAN Recipe+PEN YAN XIAO enema+dreg sextem alapplication therapy;control group had83cases that is PEN QIANG YAN Recipe. Observe clinical efficiency,Traditional Chinese medicine symptoms，physical signs and quality of life after thetreatment.Female Wistar rats were used and the CPID model was established with sleepingdeprived+ring terrified+mixed bacteria injection+mechanic injury. Seventy-two rats wererandomly divided into normal group， sham operation group， model group，taking herbsorally large，medium and small dose groups and comprehensive treatment large，mediumand small dose group. The histomorphological changes of the rats’ uteri were observedusing light microscope. The enzyme-linked immunosorbent assay (ELISA) was applied to measure the concentration of Endolhelin-l(ET-1)、Thrombus B2(TXB2) and6-ketone-prostste F1(6-keto-PGF1) in serum of rats in each group.The immunochemistrymethod was used to detect the expression of Insulin-like growth factor-1(IGF-1)、Fibroblast growth factor-2(FGF-2)and Matrix metalloproteinases-2(MMP-2) in rats’ uterine tissue.Resulqts：Clinical observation result indicates that the recovery rate of thecomprehensive healing effect、traditional Chinese medicine symptom and local sign onchronic pelvic inflammatory disease of blood stagnate and deficiency of the kidney treatedby comprehensive treatmen had been promoted:44.87%to82.67%,50%to81.33%,44.87%to73.33%;two groups relatively have a significant difference(P<0.01).Thecomprehensive treatmen can significantly promote the total score of quality of life，physicalfield,psychological field and social relations(P<0.01), significantly impromed patient’squality of life,and had the dominant of largy safety、lower recurring relate.The serous levels of ET-1、TXB2in model group were significantly higher than thosein normal group(P<0.05)；the serous levels of6-keto-PGF1in model group weresignificantly lower than those in normal group(P<0.05).The uterine tissure expression ofIGF-1、 FGF-2、 MMP-2were all significantly increased than those in normalgroup(P<0.05).After treatment，excepted taking herbs orally small dose groups,the serouslevels of ET-1、TXB2in all treatment group were significantly lower than those in modelgroups，meanwhile the6-keto-PGF1αin other treatment group were elevated. The uterinetissure expression of MMP-2in other treatment group were significantly increasedcompared with model groups(P<0.05or P<0.01); the uterine tissure expression of IGF-1、FGF-2in all treatment groups were significantly reduced compared with modelgroup(P<0.05). Comprehensive treatment large， medium dose group significantlyoutweighed the other treatment groups on ET-1、TXB2、6-keto-PGF1、IGF-1、FGF-2、MMP-2(P<0.01).Conclusions： The ComPrehensive Therapy method of promoting blood circulationand tonifying the kidney is safe and efficient, and suitable for clinical application. Themethod can adjust the levels of endothelial function cytokines and antiadhesion，thus canexpand blood vessel,improve small blood circle,increase effective blood quantity in thepelvic cavity,and remove blood stasis, effectively so as to inhibit inflammation, preventand alleviate the pelvic adhesions.更多还原