桂枝茯苓丸联合达那唑治疗子宫内膜异位症临床研究

Clinical study of Guizhi-Fuling pill combined with danazol in the treatment of endometriosis

目的探讨桂枝茯苓丸联合达那唑对子宫内膜异位症（endometriosis，EM）患者血管内皮生长因子（vascular endothelial growth factor,VEGF）、雌激素受体（estrogen receptor,ERα）及Ⅲ的影响。方法将符合入选标准的EM患者316例，采用随机数字表随机分为2组各158例。常规治疗组口服达那唑片；联合治疗组在常规治疗组基础上加用桂枝茯苓丸，均治疗28d。采用酶联免疫吸附法测定血清血管内皮生长因子（vascular endothelial growth factor,VEGF）、VEGF受体Flk-1、雌激素受体α（estrogen receptor α、ERα）、17β-雌二醇（17β-estradiol，E2）、IL-2、IL-6、IL-8水平。反转录聚合酶链反应检测异位内膜间质细胞VEGF和Flk-1mRNA表达，评价疗效及复发率。结果联合治疗组总有效率（93．7％比78．5％；x2=13．968，P〈0．01）显著高于常规治疗组，复发率（5．4％比13．7％；x2=19．984，P〈0．01）显著低于常规治疗组。治疗后，联合治疗组患者血清VEGF[（2．93±0．07）pg／ml比（6．85±0．12）pg／ml；t=354．679，P〈0．01]、Flk-1[（2．97±0．12）pg／ml比（5．87±0．17）pg／ml；t=175．179，P〈0．01]、ERa[（4．93±0．29）pg／ml比（6．85±0．37）pg／ml；t=51．337，P〈0．01]、E2[（11．69±1．09）pg／ml比（14．10±0．78）pg／ml；t=22．601，P〈0．01]、IL-2[（2．27±0．12）pg／ml比（2．31±0．16）pg／ml；t=2．514，P〈0．05]、IL-6[（0．39±0．03）pg／ml比（0．59±0．06）pg／ml；t=37．476，P〈0．01]、IL-8[（0．47±0．04）pg／ml比（0．81±0．09）pg／ml；t=43．393，P〈0．01]水平均显著低于常规治疗组，异位内膜间质细胞VEGFmRNA[（0．69±0．08）比（2．11±0．09）：t=148．229，P〈0．01]和Flk-1mRNA[（4．67±0．14）比（5．61±0．22）；t=45．311，P〈0．01]表达显著低于常规治疗组。结论桂枝茯苓丸联合达那唑可下调EM患者异位内膜间质细胞VEGF和Flk-1表达，降低血清VEGF、Flk-1、ERa和E2，减轻炎症反应，改善症状。

Objective To investigate the therapeutic effect of Guizhi-Fuling pill combined with danazol for endometriosis and its possible therapeutic mechanisms. Methods A total of 316 patients with endometriosis were recruited and randomly divided into a routine treatment group and a combined treatment group, 158 in each group. The conventional treatment group were treated by oral danazol tablets, and the combined treatment group by oral danazol and Guizhi-Fuling pill for 28 days. The serum levels of vascular endothelial growth factor （VEGF）, VEGF receptor Flk-1, estrogen receptor α （ERα）, 17β-estradiol （E2）, IL-2, IL-6 and IL-8 were detected by the enzyme-linked immtmosorbent assay. The expressions of VEGF and Flk-1 mRNAs in the ectopic endometriotic stromal cells were determined with the reverse transcriptase-polymerase chain reaction. Results The total effective rate in the combined treatment group was significantly higher than that in the routine treatment group （93.7% vs. 78.5%; x2=13.968, P〈0.01）, and the recurrence rate was significantly lower （5.4% vs. 13.7%; x2=19.984, P〈0.01）. After the treatment, the serum levels of VEGF （2.93 ± 0.07 pg/ml vs. 6.85 ± 0.12 pg/ml; t=354.679, P〈0.01）, Flk-1 （2.97 ± 0.12 pg/ml vs. 5.87± 0.17 pg/ml; t=175.179, P〈0.01）, ERα （4.93 ± 0.29 pg/rnl vs. 6.85 ± 0.37 pg/ml; t=51.337, P〈0.01）, E2 （11.69±1.09 pg/ml vs. 14.10± 0.78 pg/ml; t=22.601, P〈0.01）, IL-2 （2.27 ± 0.12 pg/ml vs. 2.31 ± 0.16 pg/ml; t=2.514, P〈0.05）, IL-6 （0.39 ± 0.03 pg/ml vs. 0.59 ± 0.06 pg/ml; t=37.476, P〈0.01） and IL-8 （0.47 ± 0.04 pg/ml vs. 0.81 ± 0.09 pg/ml; t=43.393, P〈0.01） in the combined treatment group were significantly lower than those in the routine treatment group; the expressions of VEGF （0.69 ± 0.08 vs. 2.11 ± 0.09; t=148.229, P〈0.01） and Flk-1 （4.67 ± 0.14 vs. 5.61 ± 0.22; t=45.311, P〈0.01） mRNAs in the ectopic endometriotic stromal cells in the combined treatment group were significantly lower than those in the routine treatment group. Conclusions Guizhi-Fuling pill combined with danazol can downregulate the expressions of VEGF and Flk-1 in the ectopic endometriotic stromal cells, reduce the serum levels ofVEGF, Flk-1, ERα and E2, alleviate inflammation, and improve symptoms.