Mechanisms of Ersi Decoction on Rheumatoid Arthritis Rats Induced by Bovine Type Ⅱ Collagen-solution / 中国实验方剂学杂志

ABSTRACT

ObjectiveTo observe that effect of Ersi decoction on rats with rheumatoid arthritis （RA） induced by using the complete Freund's adjuvant emulsion containing bovine type Ⅱ collagenand and elucidate underlying menchanisms involving to inhibit inflammation and joint synovial angiogenesis. MethodThe rat model of RA was established by immune induction with complete Freund's adjuvant emulsion containing bovine type Ⅱ collagen. All male SD rats were randomly divided into blank group， RA model group， methotrexate group（1.0 mg·kg-1）， and low-， medium- and high-dose group（30，15，7.0 g·kg-1·d-1）of Ersi decoction， with 8 rats in each group. Except the blank group， rats in the methotrexate group and Ersi decoction groups were given corresponding doses of methotrexate and Ersi decoction after establishment of RA induced by strengthen immunity，respectively，and those in the model group and blank group received normal saline of equivalent volume，once a day for 28 days. After the administration， the degree of joint swelling of rats in each group was analyzed by joint swelling volume and index. The small animal ultrasound imaging system was used to detect the score and area of synovial hyperplasia of knee joint in right lower limb of rats and hematoxylin-eosin（HE）staining to observe the histomorphological changes in joint synovium of rats. The levels of tumor necrosis factor-α（TNF-α） and interleukin-1β（IL-1β） were measured by enzyme-linked immunosorbent assay（ELISA）. Immunohistochemistry was employed to analyze the expression of CD31 and vascular endothelial growth factor receptor 2（VEGFR2） in in joint synovium. ResultCompared with the blank group， the model group demonstrated significant increase in joint swelling volume and index， inflammatory cytokines including TNF-α and IL-1β in serum， the score and area of synovial hyperplasia of knee joint in right lower limb， obvious pathological changes in the synovium and the expression of CD31 and VEGFR2 in joint synovium. Medium and high-dose Ersi decoction significantly alleviated the pathological changes of synovium tissue， attenuated joint swelling volume and index and decreased the expression of CD31 and VEGFR2 in joint synovium as compared with the model group. Moreover， high-dose Ersi decoction showed significantly lower levels of TNF-α and IL-1β in serum， and the score and area of synovial hyperplasia of knee joint in right lower limb. But medium-dose Ersi decoction only showed lower levels of TNF-α and area of synovial hyperplasia of knee joint. ConclusionErsi decoction could reduce synovial inflammation and hyperplasia through inhibiting synovial angiogenesis in rats with RA induced by bovine type Ⅱ collagen for achieving the effect of reducing RA joint damage， which provides an important reference for anti-RA of Ersi decoction in clinical application.