| With the development of nuclear technology and the wide application of radiology in clinical diagnosis and treatment,the probability of radiation injury is increasing.The intestinal tract is sensitive to ionizing radiation,especially the small intestine.After the whole body or the abdomen passes through the ionizing radiation,the small intestine epithelial stem cell and the intestinal gland cell are injured or dies,thus causes the intestinal tract tissue structure destruction,the function barrier,appears the intestinal tract radiation damage,when is serious occurs the intestinal type radiation sickness,even causes the death.With the increasing number of tumor patients,more and more clinical radiotherapy,especially the pelvic cavity tumor radiotherapy,injury to the intestinal tract,side effects,even led to the end of radiotherapy.During radiotherapy for pelvic and abdominal tumors,about 50%to 70%of patients have symptoms of acute gastrointestinal tract,especially diarrhea,and about 5%to 10%of these cases are life-threatening due to severe intestinal injury.In nuclear accidents（nuclear power plant,nuclear explosion）and radiation accidents（disease diagnosis,treatment,radiation processing,etc.）can cause varying degrees of intestinal radiation damage.In the face of more and more radiation damage,the research on the protection and treatment of radiation damage is particularly urgent.Radiation injury has a systemic effect,which can damage various systems and organs of the body to varying degrees.Therefore,the protection and treatment of radiation injury is still a worldwide problem.To some extent,the protection significance of radiation injury is greater than the treatment.Traditional Chinese medicine has always emphasized the importance of "treating diseases before they happen",preventing diseases before they happen and preventing existing diseases from changing have important practical significance for reducing the risk of radiation injury.Purpose:In theory,the understanding of TCM theory on the function of small intestine in western medicine is discussed,and the traditional Chinese medicine pathogenesis of acute radiation injury caused by ionizing radiation is discussed.It provides a theoretical reference for the syndrome differentiation and treatment of acute radiation of small intestine;In the experimental study,we first observed the acute injury effect of ionizing radiation on the small intestine of mice,and then explored the protective effect of Chinese medicine compound on the acute radiation inj ury of small intestine in mice.Finally,the protective mechanism of Chinese herbal compound on acute radiation injury of small intestine in mice was explored based on TLR5/NF-κB signaling pathway.Method:Theoretical research:By consulting a large number of literatures on the understanding of small intestine function by Chinese medicine and Western medicine,referring to the relevant research results of predecessors,thinking,and summarizing the understanding of TCM theory on the function of small intestine in western medicine;At the same time,consult the pathology of a large number of intestinal radiation damage,related symptoms,and the results of TCM research conducted by relevant scholars,contact the diagnosis of TCM,the etiology and pathology of the disease,and try to conduct a discussion on the pathogenesis of Chinese medicine on the new disease of intestinal radiation damage.Experimental study:Experiment 1:Male BALB/c mice were randomly divided into normal group and model group according to body weight.The normal group mice were not irradiated with radiation,and the model group mice were given whole body irradiation with2.0 Gy 60Co γ-ray.The whole condition of the fur,mental state,fecal traits,diet,activity,etc.of the mice was observed before and after the irradiation,and the body weight of the mice was recorded,and the body weight change curve was drawn.The cervical vertebrae were sacrificed 1 day and 3 days after irradiation,and the small intestine tissues of the mice were stained with HE,small intestine morphology,small intestine villus height,crypt depth,TUNEL staining apoptosis and related apoptosis genes are detected.Experiment 2:Male BALB/c mice were randomly divided into normal group,positive drug group,Chinese medicine compound high-dose group,and traditional Chinese medicine compound low-dose group.The positive drug group was given positive drug Anduolin aqueous solution to prevent gavage for 10 days before irradiation.the high-and low-dose groups of Chinese herbal compound were given the high-and low-dose aqueous solution of Chinese herbal medicine for 10 days.The normal group and the model group were given with deionized water,Ten days after the prophylaxis,the mice in each group were given a single body irradiation with 2.0 Gy 60 Co γ-rays except the normal group.The overall condition of the mice was observed before and after the irradiation,and the body weight of the mice was recorded.The cervical vertebrae were sacrificed before irradiation,1 day after irradiation,3 days after irradiation,and 7 days after irradiation.The small intestinal tissues of the mice were taken for the detection of small intestinal tissue morphology,villus height,crypt depth,small intestine tight junction protein occludin mRNA,TUNEL staining and apoptotic cell counts in the small intestine.Experiment 3:Male BALB/c mice were randomly divided into normal group,positive drug group,high dose group and low dose group according to body weight.The positive drug group was given a positive drug solution for 10 days before the irradiation.The high-and low-dose groups were given a high-and low-dose aqueous solution of Chinese herbal medicine for 10 days,and the normal group and the model group were given a control solution with deionized water.Ten days after the prophylaxis,except for the normal group,the other groups of mice were subjected to one-time whole body irradiation with 2.0 Gy 60Co y-rays.The overall condition of the mice was observed before and after the irradiation,and the body weight of the mice was recorded.The cervical spine was sacrificed before irradiation,1 day after irradiation,3 days after irradiation,and 7 days after irradiation.The mRNA expression of TLR5/NF-κB signaling pathway is detected in mouse small intestine tissue,and TLR5 and NF-κB immunohistochemistry are detected.The expression of IL-1,TNF-a mRNA in the downstream of TLR5/NF-κB pathway are detected.The expression of apoptosis-related genes Bcl-2,Bax mRNA and IL-11 mRNA are also detected.Result:1.Theoretical research shows that the theory of "spleen and stomach drop" in Chinese medicine basically summarizes the functions of digestion,absorption and excretion of the human body.Through "elimination","grinding" and "chemicalization",it shows that Chinese medicine has a very clear understanding of the digestive process of the intestines.The stomach is "received and matured",the spleen is "disappeared","grinding" and the small intestine is "accepted"."Chemical" reflects the digestive function of the modern medical gut;The intestinal absorption function of western medicine is embodied in the "secretion clearing" of the small intestine and the "transportation" and "clearing" of the spleen.Throughreducing turbidity" in the stomach,"removing turbidity" in the small intestine and"conducting" and "changing" in the large intestine,TCM realizes the excretion function of the intestinal tract in western medicine.The human body through "secrete clear turbid","conduction,change dregs","clear","turbid" exercise the function of guarding qi to resist evil,play the intestinal barrier function,protect human health;At the same time,it can be seen from the spleen "zang yi zhu si" and "si injury spleen" and "si zi qi jie" that TCM realized "brain-intestine interaction" very early,which not only has rich theories,but also is widely used in clinical practice.According to the research and analysis,the pathogenesis of TCM for acute intestinal injury caused by ionizing radiation can be summarized as follows:Evil sheng injury,lack of energy and blood source,false and solid inclusion;Lifting disorders,misperception dereliction of duty,conduction loss of division;"Hot" "wet" "toxic" "blood stasis" accumulate,damage blood collaterals;Barriers are missing and prone to deterioration.Therefore,in clinical practice,the TCM syndrome differentiation and treatment of intestinal acute injury caused by ionizing radiation should focus on the pathogenesis.In terms of treatment,it is necessary to strengthen and dispel evil,distinguish the primary and secondary,or mainly to dispel evil,and to strengthen;Or to strengthen the main,and to dispel evil;Or heal and dispel evil together.Specifically,the treatment should strengthen the spleen and invigorate qi,eliminate dampness and diarrhea,clear heat and detoxify,cool blood and activate blood circulation,restore the qi mechanism of ascending and descending,and enhance the barrier function of intestinal tract.2.Severe intestinal injury in BALB/c mice caused by one-time whole body irradiation with2.0 Gy60Co γ ray:（1）after the radiation of 2.0Gy 60Co,the mice were fed less,dispirited,slow in response,tired and less active,less static and more active,with coarse hair color and obvious weight loss.（2）pathological sections of small intestine of mice showed obvious damage to small intestine.One day later,compared with the normal group,the villi became shorter（P<0.001）,the crypt became shallow（P<0.05）,and even the villi were damaged.Three days later,the villi length recovered slightly,but there was still a significant difference between the normal group and the normal group（P<0.05）,and the crypt depth recovered well,but there was no difference between the normal group and the normal group.（3）the number of apoptotic cells in the small intestine increased sharply one day after irradiation（P<0.001）,and a large number of apoptotic cells were still present three days after irradiation（P<0.01）.One day after irradiation,the expression of anti-apoptosis gene bcl-2 mRNA was significantly decreased compared with the normal group（p<0.01）,and the expression of bcl-2 mRNA was gradually increased 3 days after irradiation.One day after irradiation,the expression of apoptotic gene Bax mRNA was significantly increased（P<0.05）,and 3 days later,it was still significantly increased compared with the normal group（P<0.01）.3.Low-dose prophylactic administration of traditional Chinese medicine compound for 10days can significantly protect BALB/c mice from acute intestinal radiation injury caused by 2.0Gy 60Co:（1）the low-dose group of traditional Chinese medicine compound can significantly improve the intestinal environment of mice and enhance intestinal function.Prophylactic administration for 10 days can increase appetite,intestinal absorption capacity of mice,weight gain;Microscopically,10 days of prophylactic administration resulted in significantly increased villi in the small intestine（P<0.05）and deepened crypt（P<0.05）.（2）low-dose prophylactic administration of traditional Chinese medicine compound for 10 days can effectively prevent rapid weight loss.Protect the intestinal mucosa from being seriously damaged by radiation,maintain the length of intestinal villi and the depth of crypt.After 1 day of irradiation,villi in the small intestine were significantly longer in the low-dose group than in the model group（P<0.001）.Three days later,compared with the model group,the low-dose dose was slightly higher than that of the model group,but there was no significant difference.Compared with the model group,the crypt depth of the low-dose group was significantly deeper than that of the model group（P<0.001）.Compared with the model group,the expression of occludin mRNA was significantly increased 1 day after irradiation（P<0.05）,and the expression of occludin mRNA was also significantly increased 3 days after irradiation（P<0.05）.Compared with the model group,low-dose prophylactic administration significantly reduced the number of apoptotic cells in the small intestine 1 day after irradiation（P<0.001）and 3 days after irradiation（P<0.05）.4.Changes of TLR5/NF-KB related pathway in the protection of traditional Chinese medicine compound against acute intestinal radiation injury in BALB/c mice induced by 2.0 Gy 60Co y rays:（1）the TLR5 and NF-KB proteins in the TLR5/NF-KB pathway had no significant effect before the administration of TCM compound.However,it did significantly reduce the expression of TLR5 mRNA and MyD88 mRNA in the pathway,but it has no effect on the expression of NF-KB mRNA.After 10 days of prophylaxis,the traditional Chinese medicine compound can significantly reduce the expression of the apoptotic gene Bax mRNA,and increase the expression of the apoptotic gene bcl-2mRNA and the cell cycle regulating 11-11 mRNA.（2）The expression of TLR5,NF-κB protein,TLR5 mRNA and MyD88 mRNA decreased significantly after 1 day and 3days after irradiation,and the IL-1 mRNA、TNF-αmRNA downstream of TLR5/NF-κB pathway showed a low expression trend 1 day after irradiation.TLR5 protein,NF-kB protein,TLR5 mRNA and MyD88 mRNA expression remained at a low level 7 days after irradiation,indicating that the Chinese medicine can maintaine the low expression of TLR5/NF-κB pathway after irradiation.（3）The expression of Bcl-2 mRNA in the model group was always low,and the Bax mRNA of the apoptotic gene was highly expressed at 1 and 3 days,indicating that the apoptosis mechanism of the small intestine was activated by radiation.After the low-dose prophylaxis of traditional Chinese medicine,the anti-apoptotic gene Bcl-2 mRNA was significantly increased,and the apoptotic gene Bax mRNA was significantly decreased,indicating that the Chinese medicine compound can prevent radiation-induced apoptosis,which may be an important mechanism of protective effect.（4）After the low-dose prophylaxis of traditional Chinese medicine compound,the expression of IL-11 mRNA in the stem cell cycle of intestinal crypt was significantly increased,which may be one of the mechanisms of protective radiation damage of traditional Chinese medicine compound.Conclusion:1.According to the theory of "spleen ascending and stomach descending",TCM basically summarizes the digestion,absorption and excretion functions of human body;Chinese medicine believes that the human body through"secreting clear turbid","conduction,change dross","clear","turbid" exercise the role of guarding qi to resist evil,play the intestinal barrier function,to protect human health;At the same time,it can be seen from the spleen izang yi zhu si " and "si injury spleen" and "si zi qi jie" that TCM realized "brain-intestine interaction" very early,which not only has rich theories,but also is widely used in clinical practice.2.The pathogenesis of acute intestinal injury caused by ionizing radiation in traditional Chinese medicine can be summarized as follows:lifting disorders,misperception dereliction of duty,conduction loss of division;"Hot" "wet" "toxic" "blood stasis" accumulate,damage blood collaterals;Barriers are missing and prone to deterioration.Therefore,in clinical practice,the TCM syndrome differentiation and treatment of intestinal acute injury caused by ionizing radiation should focus on the pathogenesis.3.The BALB/c mice were severely injured in the small intestine after the one-time whole body irradiation with 2.0 Gy 60Cv γ raysl which can be used as an animal model of acute radiation in the small intestine.4.Low-dose prophylactic administration of traditional Chinese medicine compound for 10 days can significantly protect BALB/c mice from acute intestinal radiation injury caused by 2.0 Gy 60Co.5.the Chinese medicine compound low-dose group can significantly enhance the strong intestinal function of mice,improve the intestinal environment,significantly enhance the intestinal anti-apoptosis ability of mice,and at the same time,may have a certain impact on the intestinal stalk stem cell cycle Role,these effects may be an important mechanism to protect the intestinal radiation damage;The preventive administration of traditional Chinese medicine can maintain the low expression of TLR5/NF-κB pathway and reduce the radiation-induced apoptosis,which may be an important mechanism for preventing radiation damage. |
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