| Allergic conjunctivitis is a response resulting from a reaction of allergen with IgE antibodies on mast cells in the conjunctival stroma.This reaction triggers a cascade of events resulting in the degranulation of mast cells,and releasing chemical mediators (e.g., histamine, prostaglandins and leukotrienes) into the conjunctival stroma and tears.These mediators cause vasodilation and increasing in vascular permeability, which induce ocular itching, burning, conjunctival injection,chemosis and limbal hyperemia. Corticosteroids,histamine H1-receptor antagonists,mast cell stabilizers and non-steroidal anti-inflammatory drugs, which exert antiallergenic effects by different pharmacologi-achanism,have been used to treat anaphylactic ocular disorders.Musk is the valuable traditional Chinese medicine, it has a large number of therapeutical effect in various ailments. 70's,Seth et al.reported that musk is an anti-inflammatory agent like hydrocortisone. Results of these experiments not only demonstrate the presence of a naturally occurring antihistamine-likesubstance(s)in musk but also show a wide range of activity in preventing the in vitro effects of histamine,5-hydroxytryptamine,bradykinin,prostaglandin and acetylcholine.The contraction of isolated ileum of sensitized guinea-pigs induced by antigen egg albumin and Russell's viper venom in the present investigations(Schultz-Dale reaction)were completely inhibited by musk.Such contractions are caused by the liberation of histamine and other substances due to the antigen-antibody reaction.The drugs which inhibit actions of substances such as histamine,bradykinin,5-hydroxytryptamine may be antiallergic and antianaphylactic in nature.Both these properties are found in antihistamines which act by competing with histamine receptors in tissues,and sympathomimetic drugs which act by opposite pharmacological effects.In order to inverstigate the effect and action mechanism of musk on allergic conjunctivitis,and study pharmacokinetics of musk in the rabbit eyes,the studies were performed.PART 1 STUDY ON THE CREATIVE EFFECTS OF EXPERIMENTAL ALLERGIC CONJUNCTIVITIS WITH MUSK EYE DROPS IN GUINEA PIGSOBJECTIVE:Musk not only presences a naturally occurring antihistamine-like substance(s), but also presences a wide range of activity in preventing the in vitro effects of histamine,5-hydroxytryptamine, bradykinin, prostaglandin and acetylcholine.This thesis investigate the therapeutic effects and its mechanisms of musk eye drops on allergic conjunctivitis (AC) in guinea pigs. METHODS: AC was developed by intraperitoneal injection of a mixture containing Ovalbumin(OVA) and AL(OH)3 in guinea pig, and challenged by topical instillation of OVA. supplemented with a solvent group as control which were administered NS in the same period. All the animals with AC were randomly divided into 5 groups , i.e , AC model group , three treating groups treated with musk eye drops, and group treated with dexamethasone sodium phosphate eye drops. These 5 groups together with solvent group were 6 groups totally. After one week of topical administration, the changes of guinea pigs in symptoms , histamine and OVA-specific IgE concentration of ocular tissues , and morphological features of conjunctiva were observed under light microscopy.RESULTS: Compared with the vehicle group ,the conjunctiva symptoms scale, histamine and OVA-specific IgE concentration of ocular tissues, and morphological changes scale of conjunctiva of guinea pigs in the model group were all higher. Compared with the model group, the ocular symptoms of guinea pigs in each of the musk eye drops treatment groups showed relieved (P<0.05), histamine concentration of ocular tissues in treatment group revealed (P<0.01) , and OVA-specific IgE also decreased(P<0.05), morphological changes of conjunctiva tissues were relieved in treating groups. And musk eye drops suppressed EB extravasation significantly(the EB inhibitory rat of dexamethasone phosphate group is 32.84±13.23%,high dose group of musk eye drops is 43.10±24.38%,medium dose of musk eye drops is 35.07±8.88% and low dose of musk eye drops is 27.19±10.41%).CONCLUSION: musk eye drops is effective in treating AC,and its mechanism might be through decreasing the OVA-specific IgE.PART 2 STUDY ON THE DISTRIBUTION AND PHARMACOKINETIES OF MUSK EYE DROPS FOR TOPICAL INSTILLATION IN THE RABBITSOBJECTIVE: musk eye drops has good therapeutic effect on ocular inflammation,but so far,there is no report on distribution and pahrmacokinetes of musk eye drops for topical instillation in eye tissue.This thesis study distribution and pharmacokinetics of musk eye drops in the rabbit eyes by GC.METHODS: 27 rabbits separate into 9 groups. After topical instillation with 10﹪musk solution in rabbits in 0.083,0.167,0.5,1.0,2.0, 4.0,8.0,12.0h.,put the rabbits to death,and take the tears, aqueous humor,viteous body,cornea and iris, prepare homogenate , The intraocular concentrations of muscone were measured by GC ,the pharmacokinetic parameters were calculated with 3p97 program. RESULTS: Results showed that the peak concentrations (max) of muscone in various ocular tissues were 107.52±67.07,2.15±1.49, 0.034±0.0076,2.87±1.50 and 0.013±0.0045μg?g-1/μg?mL-1 in cornea,lacrimal fluid,iris and vitreous body; The half-Life (T1/2) of vrarious tossues in cornea,lacrimal fluid,iris and vitreous body was 6.56±5.79,2.87±2.24,3.37±0.68,4.69±1.32 and 8.37±2.70 h,respectively. AUC(0→T) of various tossues was 117.83±39.17,11.57±7.16, 0.18±0.056,2.86±0.42 and 0.079±0.017μg?h?g-1 orμg?h?mL-1, respectively.CONCLUSION: The results indicate that musk is distributed there is effeetive antimicrobial concentration in various intraocurar tissues.
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