内异方对子宫内膜异位症大鼠的治疗作用以及对异位内膜VEGF、HIF-1α、NF-κB和PTEN表达的影响

Therapeutical effect Neiyifang on Endometriosis in Rats and the Effect on the Expressions of VEGF,HIF-1α,NF-κB and PTEN in Ectopic Endometrium

目的本研究通过观察内异方对子宫内膜异位症(endometriosis,EM)大鼠的治疗作用,并进一步阐明可能的作用机制。方法清洁级雌性成年(9-10周龄)未孕SD大鼠,体重190-210 g,随机分为假手术组、模型组、内异方治疗组和阳性对照组,每组最终纳入10只大鼠。大鼠在第3个动情期时采用子宫内膜自体移植法建立EM大鼠模型。造模成功后,内异方治疗组给予内异方水煎剂灌胃,阳性对照组给予达那唑溶液灌胃,假手术组和模型组大鼠给予同体积生理盐水灌胃,各组连续给药4周。治疗结束后,解剖异位内膜,采用HE染色观察异位内膜的病理形态学改变情况;采用Western blot检测异位内膜中血管内皮生长因子(vascular endothelial growth factor,VEGF)、低氧诱导因子-1α(hypoxia inducible factor-1α,HIF-1α)、第10号染色体缺失的磷酸酶(phosphatase and tensin homolog deleted on chromosome ten,PTEN)与核转录因子-Kappa B(nuclear factor-Kappa B,NF-κB)蛋白表达水平。结果HE染色结果显示,内异方改善EM大鼠的异位内膜病理学结构改变。Western blot结果显示,内异方抑制EM大鼠的异位内膜组织的VEGF、HIF-1α和NF-κB蛋白表达水平,但促进PTEN蛋白表达水平。结论内异方具有改善大鼠EM的作用,这种作用可能与抑制异位内膜组织中VEGF、HIF-1α和NF-κB蛋白表达并促进PTEN蛋白表达相关。

Objective In this study,the therapeutical effect of Neiyifang on endometriosis(EM)in rats was observed,and the underlying mechanism was elucidated.Methods Clean female adult SD rats(9-10 week-old)without pregnancy,weighing 190~210 g,were randomly divided into sham group,model group,Neiyifang treatment group and positive control group,and 10 rats were finally included in each group.EM rat model was established by endometrial autotransplantation in the third estrous phase.After the establishment of the model,the neiyifang treatment group was given neiyifang water decoction by gavage,the positive control group was given danazole solution by gavage,the sham group and the model group were given the same volume of normal saline by gavage,and each group was given medicine for 4 weeks.After the treatment,the ectopic endometrium was dissected,the histopathological changes were observed by HE staining,and the expression levels of vascular endothelial growth factor(VEGF),hypoxia inducible factor-1α(HIF-1α),phosphatase and tensin homolog deleted on chromosome ten(PTEN)and nuclear factor-Kappa B(NF-κB)proteins were determined by Western blotting.Results HE staining data showed that Neiyifang inhibited the growth of ectopic endometrium in EM rats.Western blot data showed that Neiyifang inhibited the expression levels of VEGF,HIF-1αand NF-κB proteins,however,promoted the expression level of PTEN protein in ectopic endometrium of EM rats.Conclusion Neiyifang can alleviate EM in rats,and the therapeutical effect may be related to the inhibition of VEGF,HIF-1αand NF-κB protein expression and the promotion of PTEN protein expression in ectopic endometrial tissue.