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Therapeutic Effects Of Lugua Polypeptide Injection On Adjuvant-induced Polyarthritis In Rats

Posted on:2010-04-15Degree:MasterType:Thesis
Country:ChinaCandidate:X Y HouFull Text:PDF
GTID:2144360272996938Subject:Pharmacology
Abstract/Summary:PDF Full Text Request
Rheumatoid Arthritis is a common chronic systemic autoimmune disease,and its basic pathological changes are chronic arthrosynovitis for the formation of pannus invasive, destruction of cartilage,bone and surrounding tissue.Specific reasons of the disease are not clear yet,and clinical manifestations of the disease are complex and diverse,So it lead to be lack of clinical programs to cure this disease currently,as well as measures to prevent this disease.Searching a drug can really cure the disease becomes a matter of urgency.Western medicine is only symptomatic treatment nowadays,which limited to ease the pain,reduce inflammation,reduce side effects,prevent bone changes,the protection of joints and muscle function,etc.In fact the disease can not be really controlled.With the continued use of these medcine,not only the effect of drugs reduced,also lots of adverse reactions will bring enormous physical and mental suffering to the patients;Our country has a long history of Chinese medicine theory,the use of traditional Chinese medicine theory combined with modern pharmaceutical technology will reflect certain advantages on regulation of immune function,protecting the joints tissues,maintenance of drug sensitivity,reduce toxicity of drugs and so on.Meanwhile it has opened new avenues to treating RA on the rational use of drugs.The brand name of Cervus and Cucumis Polypeptide injection is Songmeile and it is a compound preparation.It is extracted from deer bone and dry Cucurbitaceae ripe melon seeds and made into sterile aqueous solution.It contains osteoinductive peptides biology factor,sweet pumpkin seed extract,a number of free amino acids and organic calcium, phosphorus and other constituents.The treatment of rheumatoid arthritis using Cervus and Cucumis Polypeptide injection has satisfactory results.The effect is more obviously especially for young,early rheumatoid arthritis in patients with joint swelling,morning stiffness and pain relief.However,the literature has reported that Cervus and Cucumis Polypeptide injection can produce fever,rashes or even anaphylactic shock and other adverse reactions,so Yu teng pharmaceutical factory of Harbin cut the integrated polypeptide into different conponent A,B,C and also made them into corresponding injection.The experiment will be on how to improve the effectiveness of drugs to ensure drug safety,to explore the efficacy and mechanism of A,B,C also and D.This can offer a support on the study of RA new drugs developing in clinical treatment.There is lot of similarities between human RA and Adjuvant-induced arthritis on clinical,pathological and immunological performance.AA animal model is one of the best model on screening and evaluation of anti-RA drugs.Therefore,the experimental use modified Freund's complete adjuvant-induced model of adjuvant arthritis in rats,that is, the model rats were given 0.1ml subcutaneous complete Freund's adjuvant on the right rear toe.AA rat model,not only after the local joint disease(swelling,joint swelling, deformation,infiltration of inflammatory cells,etc.) in line with changes in human rheumatoid arthritis,but also appeared in AA rats weight loss,mental symptoms such as low which performance similar to human RA,that proved we obtained a successful animal model results.This experiment used preventive medication,that is,the first time medication was designed before proinflammatory,and the rats in each group were separately given drugs by conponent A 2.5mg/kg,5mg/kg,conponent B 2.5mg/kg,5mg/kg,conponent C 2.5mg/kg,5mg/kg and LPI 2.5mg/kg,to ensure the density of the drugs reaching a certain consistence when the rats was proinflammatory.In order to evaluate the effect of the drugs and searching mechanism of action,some variances were measured at different time before and after the proinflamrnatory,such as the weight change,the swelling degree in right and left hind paws,the aural region macula and the tail tubercle,PMφin rats of AA,blood rheology,serum SOD,NOS activity and content of MDA,NO,IL-1β,TNF-αand IL-6.The results indicate:1.LPI and the component A could inhibit the primary swelling of the right paws of rats,indicating that they can inhibition acute inflammatory response on the partial proinflammatory of RA primary phase.2.LPI and the component A,B could inhibit the secondary swelling of the left paws of rats obviously,meanwhile the component A can significantly improved the aural region macula and the tail of nodular lesions of secondary symptoms,shows that they have certain inhibition on the secondary phase of inflammatory autoimmune caused by cellular immunity disorder.3.LPI and the component A can significantly reduce the peritoneal macrophage phagocytosis,indicating they are on the role of inhibition of macrophage activation in RA treatment.4.LPI and the component A,B,C can significantly reduce the whole blood viscosity, while LPI and the component A also can significantly slow down the 1h and 2h ESR, shows they have a certain impact on AA rats hemorrheology. 5.LPI and the component A can significantly reduce the serum content of MAD, meanwhile LPI and the component A,B,C can significantly increase serum SOD activity, indicating that it maybe relative to the oxygen free radicals removal of the blood content of RA.6.LPI and the component A,B,C can significantly reduce the serum content of NO, TNF=αand serum NOS activity,meanwhile LPI and the component A,C can significantly reduce the serum IL-6 content,but only LPI can significantly reduce the serum IL-1 content,shows that it may be inhibiting the activation of macrophages through reducing the secretion of inflammatory cell elements,which control the development of RA.In a word,LPI has the best treatment for rheumatoid arthritis on the above model, The impact mechanism maybe relative to inhibit the activation of PMφ,decrease the levels of IL-1,TNF-αand IL-6 in serum and improving the ability of clearing oxygen-derived free radicals of the organism and the changes of hemorheology.Although component A has a good anti-inflammatory and immunomodulatory effects,but no significant effect on hemorrheology and some proinflammatory factors,component B can obviously control the secondary swelling of the left paws of rats,however,no other anti-inflammatory and immunomodulatory role,component C did not result in any significant role in inflammatory and immune regulation.This shows that the interception of physical methods of different molecular weight polypeptide component did not show a good efficacy.Whether is the problem of cut-off method,or the molecular weight between 100~1000kD is LPI best peptide need to be in-depth study.
Keywords/Search Tags:Cervus and Cucumis Polypeptide injection, Rheumatoid Arthritis, Adjuvant Arthritis, anti-inflammatory, immunity, hemorheology
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