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稳肾养雪汤改善子宫内膜容受性恢复及促进大鼠子宫内膜血管生成。

Wenshen Yangxue decoction improves endometrial receptivity recovery and promotes endometrial angiogenesis in a rat model.

机构信息

a Department of Traditional Chinese Medicine, Beijing Obstetrics and Gynecology Hospital , Capital Medical University, Beijing, PR China.

出版信息

Pharm Biol. 2018 Dec;56(1):573-579. doi: 10.1080/13880209.2018.1510973.

Abstract

CONTEXT

Wenshen Yangxue decoction (WSYXD) is a famous traditional Chinese medicine (TCM) formula and has been used in infertility treatment, but the exact mechanism is still unknown.

OBJECTIVES

To determine if WSYXD improves endometrial receptivity recovery and promotes endometrial angiogenesis in a rat model.

MATERIALS AND METHODS

A total of 100 proestrus female SPF Wistar rats were randomly assigned into five groups: control (saline), model (saline and hydroxyurea solution), high (5.2/100 g), middle (2.6/100 g) and low (1.3/100 g) WSYXD dose groups for 10 d. The microvessel densities, endometrial microstructure, as well as blastocysts number, were observed, followed by detection of angiogenesis-related gene/protein expression by immunohistochemistry, western blot and quantitative real-time polymerase chain reaction (RT-PCR), respectively.

RESULTS

Compared with the model group, the blastocyst number in WSYXD middle and high groups were significantly increased (4.50 ± 3.11 vs. 13.00 ± 2.12, 14.00 ± 1.83, p < 0.01). Lower MVD can be found in the model group (4.7) when compared with the normal control (13.7), middle (8.4) and high (9.7) dose groups. Additionally, significant differences were observed in VEGF, HIF-1α, p-AKT, p-PI3K, Ang1 and Ang2 (all p < 0.01) among different groups.

DISCUSSION AND CONCLUSIONS

In conclusion, WSYXD could help endometrial receptivity recovery and promote endometrial angiogenesis through PI3K, HIF-1α signalling and VEGF expression regulation. This study provides molecular evidence for application of WSYXD in the clinic and promotes new drug development from TCM.

摘要

温肾养血方促进羟脲诱导大鼠子宫内膜容受性恢复及血管生成的作用机制研究

背景

温肾养血方是一种著名的中药方剂,已用于治疗不孕症,但确切机制尚不清楚。

目的

研究温肾养血方对羟脲诱导大鼠子宫内膜容受性恢复及血管生成的作用。

材料和方法

将 100 只动情前期 SPF 级 Wistar 大鼠随机分为 5 组:对照组(生理盐水)、模型组(生理盐水和羟脲溶液)、高剂量组(5.2/100 g)、中剂量组(2.6/100 g)和低剂量组(1.3/100 g),连续灌胃 10 d。观察各组大鼠子宫内膜微血管密度、子宫内膜超微结构及胚胎数,免疫组化法检测各组大鼠子宫内膜组织中血管生成相关基因/蛋白的表达,Western blot 法和实时荧光定量 PCR(qRT-PCR)法检测各组大鼠子宫内膜组织中血管生成相关蛋白的表达。

结果

与模型组比较,温肾养血方中、高剂量组胚胎数明显增加(4.50±3.11 比 13.00±2.12、14.00±1.83,p<0.01)。模型组大鼠子宫内膜微血管密度(4.7)明显低于正常对照组(13.7)、中剂量组(8.4)和高剂量组(9.7)(p<0.01)。不同剂量温肾养血方组大鼠子宫内膜组织中 VEGF、HIF-1α、p-AKT、p-PI3K、Ang1 和 Ang2 表达差异均有统计学意义(均 p<0.01)。

结论

温肾养血方可通过调控 PI3K/HIF-1α 信号通路和 VEGF 表达促进羟脲诱导大鼠子宫内膜容受性恢复及血管生成,为温肾养血方的临床应用提供了分子依据,也为中药新药研发提供了新的思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6fb/6292361/afd8c06f4507/IPHB_A_1510973_F0001_C.jpg

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