Compound astragalus ligustici granule inhibits cartilage inflammation in rats with rheumatoid arthritis via TLR4/MCP-1 pathway
Objective It is to observe the effect of compound astragalus ligustici granule(CALG)on cartilage inflam-mation in rats with rheumatoid arthritis based on the Toll-like receptor 4(TLR4)/monocyte chemokine-1(MCP-1)path-way,and to explore its mechanism in the treatment of rheumatoid arthritis.Methods Fifty male SD rats were taken,in which 8 rats were randomly selected as the blank group,and the rest of the rats were modeled as collagen-induced arthritis(CIA).On the 14th day of modeling,30 successfully modeled rats were randomly divided into 8 rats in the model group,7 rats in the TAK-242 group,7 rats in the CALG group,and 8 rats in the CALG+TAK-242 group.Starting from day 15,the CALG group was given CALG solution 0.03 g/mL by gavage,once daily;the TAK-242 group was given TAK-242 3 mg/(kg·d)by intraperitoneal injection,twice per week;the CALG+TAK-242 group was given CALG solution 0.3 g/kg by gavage once daily,and TAK-242 3 mg/(kg·d)by intraperitoneal injection,twice per week;the blank group and model group were given 0.9％sodium chloride solution by gavage,once daily.Each group was continuously intervened until the 35th day.Toe swelling and arthritis index scores of the rats were recorded on days 14,17,20,23,26,29,32,and 35 after modeling,respectively;the serum levels of interleukin-1β(IL-1β),interleukin-6(IL-6),interleukin-8(IL-8),tumor necrosis factor-α(TNF-α)were determined after the rats blood was taken on the 35th day of treatment,the morphology of cartilage tissue and the number of osteoclasts were observed by HE staining and tartrate acid phosphatase(TRAP)staining,and the positive expressions of TLR4,MCP-1,IL-6,TNF-α in cartilage tissue,and CD68 in synovial tissue were detected by immunofluorescence staining.Results The toe swelling degree and arthritis index of the rats in the model group on the 14th to 35 th day of experiment were significantly higher than those in the blank group at the same time period(all P＜0.05);the toe swelling degree of the rats on the 23 rd to 35 th day of experiment and arthritis index on the 26th to 35 th day of experiment in the TAK-242 group and CALG+TAK-242 group were significantly lower than those in the model group at the same time period(all P＜0.05);the toe swelling degree and arthritis index of the rats on the 32 nd to 35th day of ex-periment in the TAK-242 group and CALG+TAK-242 group were significantly lower than those in the CALG group at the same time period(all P＜0.05);the differences in the toe swelling degree and arthritis index of the rats at each time points were not statistically significant between the TAK-242 group and CALG+TAK-242 group(all P＞0.05).The serum levels of IL-1 β,IL-6,IL-8,and TNF-α,the proportions of cells with positive TLR4,MCP-1,IL-6,and TNF-α in carti-lage tissues and the proportion of cells with positive CD68 in synovial tissues of the rats in the model group were significant-ly higher than those in the blank group(all P＜0.05),and the cartilage damage of the rats was obvious with increased os-teoblasts;the serum levels of IL-1 β,IL-6,IL-8,and TNF-α,the proportions of cells with positive TLR4,MCP-1,IL-6,and TNF-α in cartilage tissues and the proportion of cells with positive CD68 in synovial tissues of the rats in each treatment group were significantly lower than those in the model group(all P＜0.05),the cartilage damage was significantly allevia-ted,the osteoclasts were decreased,and all of the above indicators in the TAK-242 group and the CALG+TAK-242 group were significantly lower than those in the CALG group(all P＜0.05),the differences in all the indexes were not statistical-ly significant between the TAK-242 group and CALG+TAK-242 group(all P＞0.05).Conclusion Compound astragalus rhizome granules can alleviate joint inflammation and protect chondrocytes in rats with rheumatoid arthritis,which may be related to the modulation of TLR4/MCP-1 pathway activity to reduce the infiltration of inflammatory factors.
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