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The Experimental And Clinical Study On The Preventive And Therapeutic Effect Of N-acetylcysteine And Chinese Herbal Medicine On Intestine Barrier Functional Disturbance Following Radiation Injuries

Posted on:2009-07-20Degree:MasterType:Thesis
Country:ChinaCandidate:Z Z ZhangFull Text:PDF
GTID:2144360248953928Subject:Traditional Chinese Medicine
Abstract/Summary:PDF Full Text Request
Radiation is a important therapeutic tool to some tumors.One of common complications induced by abdominal irradiation is the intestinal tract injury because irradiation can cause acute enteritis that,in turn,leads to progressively reduced motility and finally,in a later phase, to fibrosis.Radiation injury may also result from mast cell induced intestinal smooth muscle cell proliferation and collagen cumulation promoting intestinal brosis and breakdown of the mucosal barrier,and result in intestine barrier functional disturbance.The radiation-induced generation of ROS and oxidative stress in cells can effectively reduced or eliminated by the antioxidant N-acetylcysteine(NAC),which can also effectively regulate the intracellular redox balance and influences radiation-mediated activation of the apoptotic pathways.It has been found that this antioxidant has protective effect on most of the organs injury following radiation exposure,such as skin,retina,lung,liver,small intestine and kidney,thus the antioxidant N-acetylcysteine can act as a radioprotector.The traditional Chinese medicine(TCM) considers that radiation is a fire-heat and toxin.Because the intestinal radiation injury subordinates to diarrhea category,TCM chooses the method of cleating heat antitoxicant and reinforcement for the prevention and therapy of intestine barrier functional disturbance following radiation injuries,meanwhile carrying out syndrome differ treatment according to everybody's accompanying syndrome,and always has a better therapeutic effect.Objective 1 The Experimental Study:To evaluate the protective effect of NAC on the small intestine of male rats after the whole abdominal region irradiation withχray.It is expected to improve our understanding of the role NAC played in modulation experimental of the recovery of radiation injury and to provide theoretical and principles for its clinic use. 2 The Clinical Study:To deeply observe the protective effect of the Western medicine combined with the Chinese herbal medicine(CHM) cleating heat antitoxicant and reinforcement on intestinal mucosal barrier of acute radiation proctitis induced by abdominal irradiation,and to evaluate the protective effect of intestine barrier functional through determining the D-lactate level and diamine oxidase(DAO) of the blood plasma.Methods 1 The Experimental Study:Sixty Spraque-Dawley male rats were divided in normal group(n=12),irrdiation group(n=12),and NAC groups(50,200,300 mg/kg body wt)(n=12).Irridation injury was induced usingχray.Irradiation consisted of a single dose of 1000cGy(source-to-skin distance,80 cm) at the abdominal region after the animals had been anesthetized with sodium thiopental(40 mg/kg body wt i.p.).NAC was started 3 days before irradiation and administered for 3 more days after irradiation.At day 3,all animals were sacrificed and then we took the terminal ileum and serum to detect indexes as below.Terminal ileum mucosal morphological observation was by light microscope and transmission electron microscopic(TEM).The terminal ileum were collected for crypt survival assay and counting of ileal villi.The activity of superoxide dismutase(SOD),the contents of malondialdehyde(MDA) and reduced glutathione hormone(GSH) in the small intestine,the blood plasma levels of D-lactate and diamine oxidase(DAO) were also measurd.2 The Clinical Study:We started this study with the aim of establishing an effective and useful therapeutic program and assessing its efficacy during a one-week period of treatment.From Jan.2006 to Feb.2008,60 patients with acute radiation proctitis(ARP),were divided into control group(n=30) and therapeutic alliance group(n=30) in Fuzhou General Hospital.One group of the patients(n=30) underwent a special one-week treatment including Western medicine Norfloxacin Capsules, Dioctahedral smectite and L-Glutamine everyday.The other group was therapeutic alliance which was given both the Western medicine above and CHM clearing heat antitoxicant and reinforcement.And there were two time points in each group(0,7day),at each time point the patients were subjected to venous sampling and blood was obtained for determination of serum D-lactic and DAO.After one-week period of treatment,statistical analysis was conducted for the total symptom scores(including abdominal pain and diarrhea) and the D-lactate level and diamine oxidase(DAO) of the blood plasma.Results 1 The Experimental Study:NAC(50,200,300 mg/kg body weight) increased crypt survival rates and the number of ileal villi of the terminal ileum(P<0.05,P<0.01), enhanced the activity of SOD and content of GSH(P<0.05,P<0.01),while deceased the concentrations of D-lactate,DAO and MDA.The above effect was dose-dependent.2 The Clinical Study:The therapeutic alliance group had a significantly lower level of the total symptom scores(P<0.01)and had a significantly lower level of the concentrations of D-lactate, DAO of the blood plasma compared with the control group(P<0.05,P<0.01).Conclusion 1 The Experimental Study:Oxygen free radicals seem to play an important role in the development of intestinal barrier impairment following radiation injurys. N-acetylcystine may be a potential agent for preventing radiation damage and can protect the small intestine from irradiation-induced injury by a crucial cytoprotective role in intestinal mucosal barrier,eliminating oxygen free radicals,keeping the internal oxidative balance, suggesting that NAC may be used as new therapy in the treatment of radiation enteritis.The antioxidant activity may be one of the mechanisms that NAC protect rats against damage induced by radiation.However,further investigations are needed to interpret the other mechanisms.2 The Clinical Study:The technique of therapeutic alliance has proven to be a promising and effective tool in the treatment of ARP induced by abdominal irradiation.For patients with radiation-induced affection of the intestinal tract the Western medicine combined with the Chinese herbal medicine(CHM) cleating heat antitoxicant and reinforcement is optimal both clinically and in terms of antioxidant activity.
Keywords/Search Tags:N-acetylcysteine, Chinese herbal medicine, clearing heat antitoxicant and reinforcement, intestinal radiation injury, intestine barrier functional, intestine barrier fiinctional disturbance
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