目的 探讨少腹逐瘀汤对子宫内膜容受性不良大鼠的改善作用及机制。方法 随机选取10只雌性SD大鼠作为对照组，其余雌性大鼠建立血瘀型子宫内膜容受性不良大鼠模型。造模大鼠随机分为模型组、戊酸雌二醇（0.27 mg/kg）组及少腹逐瘀汤低、高剂量（144、288 mg/kg）组，每组9只。给药后按2∶1安排雌性、雄性大鼠合笼，妊娠第5天剖腹观察胚胎着床率、平均胚胎着床数；采用ELISA法检测子宫内膜组织肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）、白细胞介素-6（interleukin-6，IL-6）、白细胞介素-8（interleukin-8，IL-8）水平；DCF荧光法检测子宫内膜组织活性氧（reactive oxygen species，ROS）水平；硫代巴比妥酸法检测子宫内膜组织丙二醛水平；苏木精-伊红（HE）染色法观察子宫内膜组织病理变化，记录子宫腺体数、子宫血管数、子宫内膜厚度；Western blotting法检测子宫内膜血管内皮生长因子（vascular endothelial growth factor，VEGF）、血管内皮生长因子受体2（vascular endothelial growth factor receptor 2，KDR）蛋白表达情况。结果 与对照组比较，模型组大鼠子宫内膜TNF-α、IL-6、IL-8、ROS、丙二醛水平均显著升高（P<0.05），胚胎着床率和平均胚泡着床数显著降低（P<0.05），子宫腺体数、子宫血管数、子宫内膜厚度显著降低（P<0.05），子宫内膜VEGF、KDR蛋白表达水平显著降低（P<0.05）；与模型组比较，各给药组大鼠子宫内膜TNF-α、IL-6、IL-8、ROS、丙二醛水平均显著降低（P<0.05），胚胎着床率和平均胚泡着床数显著升高（P<0.05），子宫腺体数、子宫血管数、子宫内膜厚度显著升高（P<0.05），子宫内膜VEGF、KDR蛋白表达水平显著升高（P<0.05）。HE染色结果显示，相较于模型组，各给药组大鼠子宫内膜组织较为完整，少量子宫内膜上皮细胞空泡变性，腺上皮细胞排列较为规则，固有层间质内炎性细胞浸润减少，肌层肌纤维排列较整齐，其中少腹逐瘀汤高剂量组改善更显著。结论 少腹逐瘀汤可减轻子宫内膜容受性不良大鼠氧化应激、炎症反应，改善子宫内膜容受性，提升胚胎着床率，其作用机制可能与调控VEGF/KDR通路有关。

Objective To explore the improvement effect and mechanism of Shaofu Zhuyu Decoction (少腹逐瘀汤) on rats with endometrial receptivity. Methods Ten female SD rats were randomly selected as control group. The remaining female rats were used to establish the model of dysreceptivity of endometrium. The model rats were randomly divided into model group, estradiol valerate (0.27 mg/kg) group, Shaofu Zhuyu Decoction low- and high-dose (144, 288 mg/kg) groups, each with nine rats. After administration, the female and male rats were arranged in a cage at a ratio of 2:1. On the 5th day of pregnancy, the embryo implantation rate and the average embryo implantation rate were observed by laparotomy. Levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-8 (IL-8) in the endometrium were detected by ELISA assay. Reactive oxygen species (ROS) in endometrial tissue level was detected by DCF fluorescence method. Level of malondialdehyde in endometrial tissue was detected by thiobarbituric acid method. Pathological changes of endometrial tissue were observed by hematoxylin-eosin (HE) staining method, the number of uterine glands, uterine blood vessels, and endometrial thickness were recorded. Expressions of endometrial vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor 2 (KDR) were detected by Western blotting. Results Compared with the control group, levels of TNF-α, IL-6, IL-8, ROS and malondialdehyde in endometrial of model group were significantly increased (P<0.05). Embryo implantation rate and average blastocyst implantation number were significantly reduced (P<0.05). The number of uterine glands, uterine blood vessels and endometrial thickness were significantly reduced (P<0.05). Expression levels of VEGF and KDR in the endometrium were significantly reduced (P<0.05). Compared with model group, levels of TNF-α, IL-6, IL-8, ROS and malondialdehyde in the endometrium of rats in each administration group were significantly reduced (P<0.05). Embryo implantation rate and average blastocyst implantation number were significantly increased (P<0.05). Number of uterine glands, uterine blood vessels, and the thickness of the endometrium were significantly increased (P<0.05). Expression levels of VEGF and KDR in the endometrium were significantly increased (P<0.05). HE staining results showed that compared with model group, the endometrial tissue of rats in each administration group was relatively complete, a small amount of endometrial epithelial cells were vacuolated, glandular epithelial cells arranged more regularly, the inflammatory cells infiltration in the lamina propria were decreased, the muscular muscle fibers were arranged more neatly, and the improvement in Shaofu Zhuyu Decoction high-dose group was more significant. Conclusion Shaofu Zhuyu Decoction could reduce oxidative stress and inflammation in rats with poor endometrial receptivity, improve endometrial receptivity, and increase embryo implantation rate, which mechanism may be related to the regulation of VEGF/KDR pathway.

R285.5

湖南省自然科学基金资助项目（2019JJ50459）