| Rheumatoid Arthritis(RA) is a chronic inflammation basing on the autoimmune disease and involving multiple cytokines and inflammatory mediators. It have a high incidence and a poor prognosis The cause of RA is not clear, there is no drugs could permanent control it, so searching targeted,less adverse reaction,safe and effective drugs used for preventing from and curing of RA becoming an important task.Lugua polypeptid solution(LGPS) by the sika deer animal bones and plant gourds drying ripe melon seeds were extracted by a certain made of proportion.Lugua polypeptide injection has a function of treating RA. But RA belongs to a chronic disease, need have drugs in a long time, the patient couldn't tolerance, so lugua polypeptide injection has been restricted to apply. The Gloria company manufacture LGPS basing on lugua polypeptide injection. In this study, we have investigated pharmacological effects through inflammation,immune and pain animal model and using Adjuvant Arthritis(AA) model study its function and mechanism by means of the chinese medicine technique.1. Anti-inflammatory experiment1.1 carrageenin induced rats paw swellingLGPS were given to the rats,on 7th day carrageenin was administered through subcutaneous injection inducing paw swelling, in different time the swelling degree was examined and calculated the rate of swelling. The results showed, LGPS3.5,7,14mg/kg dose all could significantly inhibite carrageenin inducing rats paw swelling. The function dependent on the dosage, the dosage more large,the inhibition more obvious.1.2 formaldehyde induced rats paw swellingReplication rat paw swelling model induced by formaldehyde, The swelling degree was examined in different time. LGPS7,14mg/kg dose could significantly inhibite rat paw swelling induced by formaldehyde.1.3 the permeability of the blood capillary in abdominal cavity of miceEvan's blue was administered through intravenous injection,LGPS 10,20mg/kg could decrease the content of Evan's blue in abdominal cavity. The results showed, LGPS could cut down the permeability of the blood capillary in abdominal cavity of mice.1.4 Leukocytoplania from the subcutaneous CMC-Na cysts of ratsAfter administration seven days,counting the number of leukocyte in CMC-Na cysts, The results showed,LGPS 7,14mg/kg dose could significantly inhibite Leukocyte from the CMC-Na cysts of rats at 3h and 7.5h of injection.1.5 granuloma induced by cotton ball in ratsAfter planting cotton ball in inguinal, LGPS were given to the rats and lasted for seven days.on 8th day ,dissection granuloma and calculate granuloma index. The results showed, LGPS 7,14mg/kg dose could significantly inhibite granuloma index, But thymus index, spleen index and adrenal index did not change significantly.2. The effect of LGPS on immune system2.1 Delayed type hypersensitivity experiment Mice sensitization by DNCB-acetone, examining part of the abdominal blue OD ,evaluation the Delayed type hypersensitivity of mice. The results showed, LGPS 10,20mg/kg dose could significantly inhibite Delayed type hypersensitivity of mice.2.2 Carbon Clearance TestMeasuring the rate of carbon clearance that could test the function phagocytose system. The results showed, LGPS had no effect to phagocytose system.2.3 Lymphocyte Transformation Experiment The incremental reaction of mouse lymphocyte was observed by the activity of spleen cell to mitosis ConA. The results showed that LGPS 20mg/kg dose could significantly cut down stimulate index, LGPS have the effect of inhibiting the Tlymphocyte transformation.2.4 Serum hemolysin experimentRBC chickens immunized by intraperitoneal injection,Examing the content of the serum hemolysin Lugua Polypeptide Solution 10, 20mg/kg dose could decrease the content of the serum hemolysin, it showed that LGPS 10, 20mg/kg dose have the effect of inhibiting the function of B lymphocyte.3. the effect of analgesic activity3.1 writhing experimentUsing acetic acid-induced mouse writhing, Noting the times of mouce writhing and latent period. The results showed,LGPS hasn't notable action on relieving acetic acid-induced mouse pain and extending the delitescence.3.2 hot-plate experimentThe hot-plate experiment proved that LGPS couldn't improve the threshold of pain in hot plate experiment in different time period.3.3 light-hot experimentThe results showed LGPS couldn't improve the threshold of pain in light-hot experiment in different time period.4. Therapeutic Effects of LGPS on Adjuvant Arthritis in Rats and its MechanismOn 8th day that the arthritic model of rats was induced by Freund's adjuvant, Lugua Polypeptide Solution (in dosage of 3.5,7,14mg/kg) were given to the rats via intragastric administration once a day and lasted for sixteen days, The swelling degree in both hind paws were examined at different time after treatment and calculate the rate of swelling. After ninteen days of treament, PMφ'function was evaluated, the content of PGE2 in inflammatory tissue fluid was measured;the changes of hemorheology was determined; the contents of TNF-α, IL-1β, IL-6, MDA, NO and SOD in serum were measured in all groups. The results showed The primarily swelling in right hind paw and the secondum swelling in left hind paw were relived significantly , the function of PMφ, the blood viscosity of 5/s,80/s,160/s and erythrocyte sedimentation rate were reduced significantly;at the same time, the contents of TNF-a, IL-1β,IL-6, MDA and NO in serum were decreased significantly,and activity of SOD was increased notably, but the content of PGE2 in inflammatory tissue fluid has no significant change.LGPS have anti-inflammatory effect and can inhibite the activity of the immunity. But LGPS doesn't show analgesic activity. LGPS has therapeutical effect to AA, which may be by inhibiting the activation of PMφ,enhancing the rat's capability of eliminating the free radicals, decreasing the levels of TNF,IL-1βand IL-6 in serum and improving the changes of hemorheology. This research provide scientific grounds for treating RA. |
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