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| Discuss on the therapeutic effect and mechanism of sinomenine on osteo-arthritis |
| CAO Juan1 YAO Yao2 LI Lingling1 CHEN Xiaolin1 XIAO Yunyun1 WU Wenhui1 DING Congzhu1 |
1.Department of Geriatrics, Drum Tower Hospital Affiliated Nanjing University Medical College, Jiangsu Province, Nanjing 210008, China;
2.Department of Pharmacy, Drum Tower Hospital Affiliated Nanjing University Medical College, Jiangsu Province, Nanjing 210008, China
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Abstract Objective To study the therapeutic effect and mechanism of sinomenine (SIN) on rabbit osteoarthritis (OA) model. Methods A total of 15 normal healthy adult New Zealand rabbits with body weight of 2.5-3.0 kg were randomly divided into control group, osteoarticular model group (OA group), and sinomenine treatment group (SIN group), with five rabbits in each group. The control group was injected with normal Saline in joint cavity, the OA group and SIN group were injected with a mixture of 4% Papain injection and 0.03 mol/L L-cysteine (2∶1) at 0.1 ml/kg intraarticular cavity, respectively. Three injections were given on the 1st, 4th and 7th day respectively. After two weeks of modeling, the knee joint of rabbits showed swelling and movement disturbance, and the modeling was successful, after OA modeling was successful, SIN group was given 30 mg/(kg·d) SIN Hydrochloride sustained-release tablets by intragastric administration, the drug was administered continuously for 15 days. No special treatment was given to OA group and control group. Serum levels of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), matrix metalloproteinase-1 (MMP-1), MMP-13, Collagen Ⅱ, and cartilage oligomer matrix protein (COMP) were detected in rabbit blood samples after four weeks. Joint pathological anatomy was observed. The expression levels of Collagen Ⅱ, polyproteoglycan and aging-related genes p21 and p53 were detected by immunohistochemistry in rabbit cartilage tissues of each group. Results After four weeks, the serum levels of IL-1β, TNF-α, MMP-1, MMP-13, Collagen Ⅱ, and COMP in OA group were higher than those in control group (P＜0.05); the levels of IL-1β, TNF-α, MMP-1, MMP-13, Collagen Ⅱ, and COMP in SIN group were lower than those in OA group (P＜0.05). Gross specimen observation showed that the joints of the control group were normal, the joint cavity of the OA group had an equal amount of joint effusion, synovial edema, and rough articular cartilage surface, while the joint cavity of the SIN group had less effusion and improved synovial congestion. Compared with the control group, the articular surface of the knee cartilage in OA group was not smooth, the cartilage was obviously thinner, the synovial membrane was infiltrated by a large number of inflammatory cells, and the synovial membrane hyperplasia and edema were obvious, the infiltration of synovial inflammatory cells, edema, and cartilage injury in SIN group were less than those in OA group. Immunohistochemical detection showed that the expression levels of p21 and p53 in OA group were higher than those in control group (P＜0.05), and the expressions of p21 and p53 in SIN group were lower than those in OA group (P＜0.05). The expression of polyproteoglycan in OA group was lower than that in control group, and the expression in SIN group was higher than that in OA group. There were no significant differences in the expression of type Ⅱ collagen among all groups (P＞0.05). Conclusion SIN has a therapeutic effect on OA, which is related to inhibiting the secretion of inflammatory factors and MMP, and inhibiting the senescence of chondrocytes, providing a theoretical basis for the use of SIN in OA treatment.
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