Xue Ping Tablets treat abnormal uterine bleeding via VEGF-ERK1/2 pathway

Abstract

Objective: To investigate the protective effects against abnormal uterine bleeding (AUB) and possible mechanisms of Xue Ping tablets (XPT) using a rat model. Methods: A total of 58 unmated female and 25 male SPF SD rats aged 8–9 weeks were selected. Eight unmated female rats were selected as the blank control group according to the complete random method. The other 50 rats were mated in a female/male ratio of 2:1. In the morning after mating, vaginal smears were collected. Presence of vaginal plug or sperm was regarded as the first day of pregnancy. All pregnant rats were given 8.3 mg/kg of mifepristone by gavage at 8:00 a.m. and 100 μg/kg misoprostol by gavage at 6:00 p.m. on the seventh day of pregnancy to induce incomplete abortion, thereby establishing a rat model of AUB. Forty rats were randomly divided into model, low- (220 mg/kg), medium- (441 mg/kg), high-dose (882 mg/kg) XPT, and positive control groups. The positive group was given 130 mg/kg Gong Xue Ning (GXN). The model group and the blank group were given an equal amount of distilled water. Results: Compared with the model group, the volume of bleeding in the positive and middle- and high-dose XPT groups decreased (P < 0.05). Moreover, compared with the model group, the progesterone levels in the positive and XPT groups were significantly increased. Immunohistochemistry showed that XPT significantly decreased the expression levels of VEGF, p-ERK, NF-κB, SAA, MMP-2, MMP-9, TIMP-1, TIMP-2 and TIMP-3. WB results showed that XPT significantly decreased the expression levels of p-ERK, MMP-9, NF-κB, MMP-2 and VEGF. QRT-PCR results showed that XPT significantly decreased the expression levels of VEGF, NF-κB, SAA, MMP-2, TIMP-1, TIMP-2 and TIMP-3 (P < 0.05). Conclusions: XPT could reduce AUB by inhibiting the inflammatory factors involved in the VEGF-ERK1/2 pathway.

Keywords

• Abnormal uterine bleeding
• Inflammatory factors
• VEGF
• ERK1/2
• Xue Ping tablets