消癥止痛汤联合脑针治疗子宫内膜异位症大鼠的作用机制探讨

A study on the action mechanism of the Xiaozheng Zhitong decoction plus brain acupuncture on endometriosis rats

目的:通过观察消癥止痛汤及脑针对子宫内膜异位症(Endometriosis,EMs)大鼠模型血管内皮生长因子(Vascular Endothelial Growth Factor,VEGF)、促血管生成素-2(Angiopoietin-2,Ang-2)、异位病灶及其周围组织中对神经纤维蛋白质基因产物9.5(Protein Gene Product 9.5,PGP9.5)表达阳性的神经纤维密度、脑源性神经营养因子/酪氨酸激酶受体B(Brainderived Neurotrophic Factor/Tyrosine Receptor Kinase B,BDNF/TrkB)信号通路的影响,从抗神经血管生成的角度探讨其治疗机制。方法:采用自体移植法对SD大鼠进行EMs造模,将造模成功的32只大鼠随机分为4组,每组8只,分别为模型组、中药组、脑针组和针药结合组,6只未造模的大鼠作为假手术组,根据分组情况给予灌胃给药及脑针治疗,4周后,分别用酶联免疫吸附剂测定法(Enzyme-Linked Immunosorbent Assay,ELISA)对大鼠静脉血清中VEGF、Ang-2水平进行测定,用免疫组化(Immunohistochemistry,IHC)法对异位病灶中PGP9.5进行测定,用蛋白质免疫印迹(Western Blot)法对BDNF/TrkB信号通路中的关键因子BDNF和TrkB蛋白进行测定。结果:在VEGF、Ang-2、PGP9.5水平上,与假手术组相比,模型组明显升高,中药组、脑针组干预后均有所下降,且中药组效果优于脑针组,针药结合组下降最为明显;在BDNF和TrkB蛋白表达水平上,与假手术组相比,模型组明显上调,中药组及脑针组有所下调,中药组效果优于脑针组,且针药结合组和中药组的表达差异无统计学意义。结论:消癥止痛汤联合脑针对EMs具有治疗作用,其作用机制可能是通过改善VEGF、Ang-2、PGP9.5水平,调节BDNF/TrkB信号通路中的关键因子BDNF、TrkB,从而抗神经血管异常生成而实现的。

Objective:By investigating the influences of the Xiaozheng Zhitong decoction(消癥止痛汤)plus brain acupuncture on the expressions of VEGF,Ang-2,PGP9.5-positive nerve fiber density in ectopic lesions and surrounding tissues,and BDNF/TrkB signaling pathway in EMs rats model,the action mechanism of the Xiaozheng Zhitong decoction plus brain acupuncture on EMs was discussed from the aspect of anti-neuroangiogenesis.Methods:SD rats were modeled with EMs by autologous transplantation method.The 32 rats that were successfully modeled were divided into 4 groups randomly,with 8 rats in each group,namely the model group,the TCM medicine group,the brain acupuncture group,and the acupuncture-decoction group.The other 6 unmodeled were sorted into the sham operation group.According to the grouping,intragastric administration or brain acupuncture were given to the rats model for 4 weeks.Results:Compared with the sham operation group,the expressions of VEGF,Ang-2,and PGP9.5 in the model group were increased obviously,and in the TCM medicine group and the brain acupuncture group were decreased significantly,and the efficacy in the TCM medicine group was better than the brain acupuncture group.The decrease of the above indicators in the acupuncture-decoction group was the most significant.The expressions of BDNF and TrkB in the model group was obviously increased compared with that in the sham operation group,in the TCM medicine group and the brain acupuncture group were decreased,and the efficacy in the TCM medicine group was better than the brain acupuncture group.There was no significant difference between the acupuncture-decoction group between the TCM medicine group in the expressions of BDNF and TrkB.Conclusion:The Xiaozheng Zhitong decoction plus brain acupuncture shows therapeutic effects on EMs.Its action mechanism may be achieved by ameliorating VEGF,Ang-2 and PGP9.5 levels,and regulating the levels of key factors BDNF and TrkB in the BDNF/TrkB signaling pathway,so as to prevent abnormal neuroangiogenesis.