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研究表明,化疗后口腔溃疡的养阴生肌散通过环氧化酶-2(COX-2)/前列腺素 E2(PGE2)通路抑制炎症和促进伤口愈合。

Study on the inhibition of inflammation by the cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) pathway and the promotion of wound healing of oral ulcer of Yangyin Shengji powder after chemotherapy.

机构信息

Department of Otolaryngology, Wuxi Hospital Affiliated to Nanjing University of Chinese Medicine, Wuxi, China.

Department of Traditional Laryngology, Wuxi Hospital Affiliated to Nanjing University of Chinese Medicine, Wuxi, China.

出版信息

Ann Palliat Med. 2021 Dec;10(12):12716-12726. doi: 10.21037/apm-21-3496.

Abstract

BACKGROUND

To investigate the treatment effect and mechanism of Yangyin Shengji powder in oral ulcer after chemotherapy.

METHODS

The experiments were externally administered. The threshold of pain reflex (Tr) was measured 30, 60, and 120 min after the last relative substances administration to the plantar and abdomen of mice by intelligent hot plate instrument. The toe swelling degree of mice was calculated 1, 3, and 5 h after inflammation. The levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), and prostaglandin E2 (PGE2) were determined by enzyme-linked immunosorbent assay (ELISA), and the relative expression levels of cyclooxygenase-1 (COX-1) and COX-2 were determined by reverse transcription polymerase chain reaction (RT-PCR) and Western blot. Two hours after the last spraying treatment, the ulcer area of mice was measured. Tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), epidermal growth factor (EGF), and epidermal growth factor receptor (EGFR) were detected by ELISA. The degree of oral mucosal injury was observed by hematoxylin and eosin (HE) staining.

RESULTS

Compared with positive control group, the Tr value of Yangyin Shengji powder group was lower at 30 and 60 min, and the Tr value was higher at 120 min. Yangyin Shengji powder decreased the swelling degree of toes 1, 3, and 5 h after inflammation, and the SOD and GSH-Px levels in the swelling tissue of toes were significantly increased. The MDA, PGE2, COX-1 and COX-2 levels were significantly decreased. The oral mucosa structure of mice in the Yangyin Shengji powder group was relatively intact and a few inflammatory cells were infiltrated. Compared with normal group, the levels of TNF-α and IL-6 in the model group were increased, while the levels of EGF and EGFR were decreased (P<0.01). Compared with the model group, ulcer area, TNF-α, and IL-6 levels were decreased in the Yangyin Shengji powder group, while EGF and EGFR levels were increased (P<0.01).

CONCLUSIONS

Yangyin Shengji powder has anti-inflammatory and analgesic effects, is anti-oxidative stress, inhibits inflammatory response, and inhibits the COX-2/PGE2 signaling pathway, so as to alleviate local inflammation of oral ulcer in mice after chemotherapy and promote wound healing.

摘要

背景

研究养阴生肌散治疗化疗后口腔溃疡的疗效及机制。

方法

实验采用局部给药,末次给药后 30、60、120 min 采用智能热板仪测定小鼠足底及腹部痛觉反射阈(Tr);末次给药后 1、3、5 h 测定小鼠足趾肿胀度;采用酶联免疫吸附试验(ELISA)测定超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、丙二醛(MDA)、前列腺素 E2(PGE2)水平,逆转录聚合酶链反应(RT-PCR)和 Western blot 法测定环氧化酶-1(COX-1)和 COX-2 的相对表达水平;末次给药后 2 h 测量小鼠溃疡面积,ELISA 法检测肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、表皮生长因子(EGF)、表皮生长因子受体(EGFR)水平;苏木精-伊红(HE)染色观察口腔黏膜损伤程度。

结果

与阳性对照组比较,养阴生肌散组 30、60 min Tr 值较低,120 min Tr 值较高;养阴生肌散组可降低炎性肿胀足趾 1、3、5 h 的肿胀度,显著提高肿胀组织中 SOD 和 GSH-Px 水平,降低 MDA、PGE2、COX-1 和 COX-2 水平;养阴生肌散组小鼠口腔黏膜结构相对完整,少量炎性细胞浸润;与正常组比较,模型组 TNF-α、IL-6 水平升高,EGF、EGFR 水平降低(P<0.01);与模型组比较,养阴生肌散组溃疡面积、TNF-α、IL-6 水平降低,EGF、EGFR 水平升高(P<0.01)。

结论

养阴生肌散具有抗炎镇痛作用,抗氧化应激,抑制炎症反应,抑制 COX-2/PGE2 信号通路,从而减轻化疗后口腔溃疡小鼠的局部炎症反应,促进创面愈合。

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