Based On "the Spleen Is The Guard" To Explore The Protective Research Of Yiqi Jiedu Fang On Acute Radiation Injury In Mice

ObjectiveThis research is based on the theory of "spleen as the guard".In theoretical study,we explored the etiology and pathogenesis of acute radiation injury(ARI),and revealed the principles of prevention and treatment of ARI directed by TCM theory.In experimental research,the injuries of spleen and intestinal immunity induced by ionizing radiation were summarized,and the protective effect of Yiqi Jiedu(YQJD)decoction was explored.Finally,we investigated the potential protective mechanism of YQJD decoction through molecular biological experimental technology.MethodsTheoretical research:(1)In order to reveal the origin and connotation of "spleen as the guard" theory,we read and analyzed many references from the ancient records of traditional Chinese medicine and cases in modern clinic.(2)To explore the etiology and pathogenesis of ARI,we analyzed the clinical manifestations of radiation injuries,and explored the pathogenesis of each stage of ARI from "spleen losing the guard".(3)According to the revealed etiology and pathogenesis,we demonstrated the prevention and treatment methods of ARI from "tonifying Qi and replenish spleen,clearing heat and relieving toxin ".Experimental study:(1)Mice were treated with 2.0 Gy 60Co γ-rays total body irradiation(TBI).The injuries of spleen and intestinal immunity were observed on day 1,3,7,14 and 21 after irradiation.(2)After 10-days’pretreatment,mice were radiated with 2.0 Gy 60Co γ-rays.The protective of YQJD decoction on spleen and intestinal immunity was measured at 1st,3rd,7th days after TBI.(3)After 10-day period intervention,mice were whole-body irradiated with 2Gy 60Co γ-rays and sacrificed on 1st,3rd,7th day after irradiation.The indicators of ferroptosis were measured to explore the potential protective mechanism of YQJD decoction.ResultsTheoretical study:(1)the theory of "spleen as the guard",originates from the yellow Emperor’s Inner Classic,has been continuously improved and developed through the interpretation and supplement of medical experts of all dynasties.According to the literature research,we indicated that the connotation of "spleen as the guard" is as follow:Spleen mainly transports the essence of water and grain,nourishes muscles and resists external evils.Spleen is the source of Zang-Fu organs,and can prevent disease transferring to other organs.Spleen is the source of Qi and blood,which can defend external evils.(2)By analyzing the clinical manifestations of each stage of ARI,we discuss the pathogenesis of this stage from the perspective of "spleen loss its guard".We believe that at the beginning of ARI,the pathogenesis of the disease is "ionization toxin attack body,making spleen(stomach)and defensive Qi injury ";at the stage of disease development and change,the pathogenesis of the disease is "spleen loss its guard,which exacerbates the irradiation injury ";at the stage of disease prognosis,the pathogenesis is " spleen dually recovers to anti ionization toxin ".(3)We think that before being radiated,we need to reinforce healthy qi so as to prevent radiation injury from occurring.Therefore,herbs which tonify qi and blood should be mainly used,and assisting with herbs clearing heat and promoting fluid production,cooling blood and invigorating blood circulation.After radiation,in order to prevent from deterioration and improve recovery,herbs clearing heat and relieving toxin should be used as the same importance of herbs tonifying qi and blood,and reinforcing essence.When the radiation injury is cured,we need to use herbs to replenish spleen and stomach,assisting with those nourishing yin and fluid,so as to regulate the functions of Zang-Fu organs and rebalance yin-yang to prevent recurring.Experimental studies:(1)The significant injury of total body in mice could be observed on the first day after irradiation.With the development of disease,spleen injury was aggravated at 3rd day after irradiation,and reduced on day 7.(2)YQJD decoction has a certain protective effect on spleen and intestine immune injuries induced by by 2.0 Gy 60Co γ ray.It can inhibit the decrease of immune cells in spleen and intestines after irradiation,promote the recovery of immune cells,improve the tissue structure of spleen and intestines,improve the distribution of immune cell subsets in spleen and intestines after irradiation,regulate the secretion of relevant cytokines after irradiation,and then promote the recovery of immune balance,and reduce the oxidative damage of spleen and intestines caused by ionizing radiation.(3)YQJD decoction can reduce the level of oxidative stress,inhibit iron overload and regulate LPCAT3/LOX pathway,so as to inhibit the cell ferroptosis and play a role of radiation protection.Modern pharmacology research shows that some drugs or their active components in the decoction have anti-oxidation or antiradiation effects,which may be the potential material basis of YQJD decoction on radiation protection.ConclusionOur study showed that "spleen loses its guard" is an important pathogenesis of ARI.YQJD decoction,which conforms to the protection principle of "tonifying Qi and replenish spleen,clearing heat and relieving toxin",attenuated irradiation induced spleen and intestinal immunity injury in mice.Its potential mechanism was related to the inhibition of ferroptosis after irradiation.