| Esculetin is the valid active composition of natural medicine ash bark to have an important pharmacological role. Ash bark usually appears in prescription of the Chinese herbal medicine of the anti-osteoarthritis, but it's concrete mechanism isn't quite clear yet. Therefore, this experiment will determine effect of esculetin in repair of osteoarthritics by observing effect of esculetin on\ nitric oxide (NO), prostaglandin E2 (PGE2) of synovial fluid and matrix metalloproteinase-1 (MMP-1) of cartilage in the model of experimental knee osteoarthritis. At the same time, this experiment will confirm the mechanism of it's prevention and curing osteoarthritis and provide effective medicine of low price for clinic. This experiment takes 24 flap-eared Japanese white rabbits (female and male rabbits each half) to be randomly divided into control group A (sham operation group), control group B and treatment group C (little dosage group), treatment group D(more dosage group). OA was induced in 18 rabbits by anterior cruciate ligament transaction (ACLT) to establish mode of OA. And other 6 rabbits (sham operation group) received unilateral knee arthrotomy as sham operation control. From the second day after operation, stomachs of treatment group C were perfused with little dosage esculetin 100 mg/kg per day, stomachs of treatment group D were perfused with more dosage esculetin 200 mg/kg per day and control group were all given normal saline. All rabbits were killed at 8 weeks post-surgery, synovial fluid were collected, and NO and PGE2 were examined. The expression of MMP-1 of cartilage were detected by immunohistochemistry. Samples of joint were collected for gross and light microscopic observation to know gross changes of femoral condyle articular facet and pathologic changes of articular cartilage cells. The data were managed with paired t-test by SPSS 10.0. As a result hinted: The femoral condylar cartilage in the control group A showed normal histologic character that cartilage was smooth and transparent, stained evenly, and few cartilage cells were distributing evenly. While femoral condylar cartilage in control group B showed obviously pathologic changes such as osteophyte, the area of cartilage degeneration mainly concentrating in medial part of medial femoral condyle, the color and luster of cartilage being murky grey, articular cartilage erosion and ulceration as mainly changes, uneven matrix staining and decrease in stain, cartilagecells reducing and distributing unevenly, cartilage cells clustering, and a lot of necrotic cartilage cell. Cartilage degeneration in treatment group was significantly slighter than that in control group B. Articular facet in treatment group was only coarse, the color and luster of articular was slightly dark, and articular cartilage in treatment group C showed erosions, less ulceration, basically even stain of cartilage matrix, a lot of hyperplastic cartilage cells and their irregular arrangement. The levels of MMP-1, NO, PGE2 in treatment group were significantly lower than those in control group B (P<0.05), and those in treatment group D were the lowest (PO.01). Therefore we can draw a conclusion: Esculetin can significantly reduce the levels of MMP-1 in cartilage and NO, PGE2 in synovial fluid, and postpone the episode of OA. With the increase of it's dosage, esculetin's inhibition is more obvious.
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