| Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the synovium. Now people have considered that the RA is related to autoimmune factors, genetics, infection and psychological factors, meanwhile inflammatory mediators and cytokines play a key role in inflammation and joint damage of RA. Although its causes have not been fully clear yet, it has been recognized that interleukin-1β(IL-1B) and tumor necrosis factor-a (TNF-a) are expressed with high level in RA patients. A paper has reported that the active substances, methyl linoleate and methyl linolenate, extracted from plants can inhibit the expression of hIL-1βgene of THP-1 cell. A result of research showed that LPS and IL-1B can increase the expression of tissue factor, which can lead to blood coagulation in vascular endothelial cells and thrombosis. Linoleic acid and linolenic acid can inhibit the expression of the tissue factor. This study investigated the inhibitions of linoleic acid and its methylester on IL-1B and TNF-a for the development of the new drug to rheumatoid arthritis.Objective (1)To research the treatment of linoleic acid and methyllinoleate on adjuvant arthritis (AA) rats; (2) To investigate the transdermal absorption of methyllinoleate for the development of the new drug to rheumatoid arthritis.Methods (1)To determine the transdermal absorption rate of methyllinoleate with modified Franz diffusion cell,and further to investigate the influence of dimethyl sulfoxide (DMSO) on the percutaneous absorption rate of methyllinoleate.(2) 30 female SD rats were divided randomly into blank group (group A), model group (group B), linoleic acid high dose group (group C), low dose (group D), methyllinoleate group (E group). Except for the rats of A group,the others were intracutaneously injected with 0.1 ml of Freund's complete adjuvant in the right hindlimb. After model establishment, the group A and B were intragastrically administered 0.4ml physiological saline, the group C and D were intragastrically administered 0.4ml and 0.2ml linoleic acid respectively, and the group E were inuncted with methyllinoleate once a day for 28 days. The rats were weighed and their paw inflammations were assessed by arthritis index once a week, and then all the rats were killed. Their spleens and thymuses were weighed. The organ indexes were calculated. The serumal TNF-a and IL-1B leves were measured by ELISA.Results (1)Percutaneous absorption experiments showed that methyl-linoleate have discovered a certain capacity of transdermal absorption, and as time goes on, the amount of progressively increased, but the effect of dimethyl sulfoxide (DMSO) on percutaneous absorption of methyllinoleate was not obvious. (2)①The protective effect of linoleic acid and methyllinoleate on adjuvant arthritis:treatment group lived well and had weaker arthrocele than those in model group.Compared with other groups, the weight of group C increased rapidly, The spleen index of group C and group E was significantly compared with the model group (P<0.05), thymus index is not obvious.②Compared with model group, IL-1βlevels of group D and group E were significantly lower (P<0.05), TNF-a levels of group C and group E decreased significantly(P<0.05, P<0.01); compared with blank group, all have improved.Conclusions (1) Linoleic acid and methyllinoleate can significantly improve the clinical situation of rats with adjuvant arthritis, reduce the joints swelling. (2) Methyl linoleate displayed a certain capacity of transdermal absorption, but the role of penetration aid of DMSO was not obvious. (3) linoleic acid and methyllinoleate can lower the level of IL-1βand TNF-a in the blood serum of AA rats. |
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