Research Article: Changrui enema inhibits inflammation-induced angiogenesis in acute radiation proctitis by regulating NF-κB and VEGF 1

Date Published: July 06, 2020

Publisher: Sociedade Brasileira para o Desenvolvimento da Pesquisa em Cirurgia

Author(s): Jinsheng Gao, Yousong Li, Xi Yang, Min Hu, Jie Xu, Lin Cheng, Kaiqi Cao, Likun Liu, Xixing Wang.


Changrui enema, a traditional Chinese medicine prescription, is used as a supplementary treatment for acute radiation proctitis (ARP). Herein we explored the inhibition effects of Changrui enema on NF-κB and VEGF in ARP mice.

A total of 120 C57BL/6 mice were divided randomly into normal mice group, ARP mice group, western medicine enema group (dexamethasone combined with gentamicin), and Changrui enema group. ARP mice were established by pelvic local irradiation. The expression of IL-1β, NF-κB, VEGF, AQP1, AQP3, p-ERK1/2 and p-JNK was determined by immunohistochemistry or western blot.

The study firstly found that Changrui enema alleviated ARP mice. The expression of IL-1β, NF-κB, VEGF, AQP1 and p-ERK1/2 was increased in ARP mice, and was reserved by Changrui enema. However, the expression of AQP3 and p-JNK was decreased in ARP mice, and was up-regulated by Changrui enema.

Changrui enema is an effective treatment with fewer side effects for ARP. The mechanism of Changrui enema may be related to the inhibition of inflammation-induced angiogenesis. Changrui enema inhibits IL-1β and NF-κB expression as well as VEGF expression. Interestingly, AQP1 promotes angiogenesis, while AQP3 inhibits inflammation. Changrui enema probably inhibits AQP1 expression by down-regulating p-ERK1/2, and improves AQP3 expression by up-regulating p-JNK.

Partial Text

Radiation proctitis is the most common radiotherapy side effect1 of abdominal and pelvic malignant tumors, such as colorectal cancer, ovarian cancer, prostate cancer and bladder cancer etc. The acute and chronic radiation proctitis incidence is 50%-75% and 5%, respectively2 . Patients with radiation proctitis mainly suffered from abdominal pain, diarrhea, excretion of mucus or blood and so on. Therefore, radiation proctitis results in poor quality of life, radiotherapy failure, and unfavorable prognosis of the patients. Unfortunately, radiation proctitis therapies for radiation proctitis are less effective and have more side effects.

Radiation proctitis is one of the most common complications of abdominal and pelvic radiation. There are various treatments for radiation proctitis and these include medical therapies, hyperbaric oxygen and endoscopic therapies20 . Many medical therapies have been proposed and developed, including anti-inflammatory agents (sulphasalazine, balsalazide and mesalazine), antioxidants (vitamin A, E and C)21 , 22 , mucosal protectants (formalin, sildenafil and mesenchymal stem cell)23 , 24 and so on. Apart from medical therapies, hyperbaric Oxygen appears to be an effective therapy for radiation proctitis according to some clinical trials25 . In addition, endoscopic therapies have also been developed for the treatment of radiation proctitis, including laser therapies26 , 27 , argon plasma coagulation28 , 29 , radiofrequency ablation30 , 31 and cryoablation32 , 33 . However, these therapies of radiation proctitis still remain unsatisfactory and novel treatments are urgently needed. Available literature34 has found that TCM may have a great potential effect in the treatment of radiation proctitis. A preliminary randomized controlled clinical trial found that Aloe vera was a safe and effective therapy for ARP. Aloe vera not only relieved diarrhea and fecal urgency scores, but also improved the quality of life of ARP patients35 . We found that retention enema with TCM compound prescription Changrui enema was an effective treatment of ARP in clinical application.

Our study firstly found that TCM compound prescription Changrui enema alleviated ARP mice. Changrui enema decreased general signs score and rectal tissue pathological grades of radiation proctitis in mice. The mechanism of Changrui enema might be related with the inhibition of inflammation-induced angiogenesis. Changrui not only inhibited inflammation factors IL-1β and NF-κB and angiogenesis factor VEGF, but also increased anti-inflammation factor AQP3 and decreased angiogenesis related factor AQP1. Together with these results, this study innovates the pathogenesis of ARP and provides a new effective treatment of ARP by using enema of TCM. However, some questions remain unanswered, for example we do not know the specific interaction between aquaporin and MAPK signaling pathways. Further studies should be carried out to investigate the molecular mechanism involved in AQP1, p-ERK1/2, AQP3 and p-JNK.




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