摘要
背景:前期研究发现,龙鳖胶囊能消除膝骨关节炎大鼠膝关节肿胀,降低血清炎性细胞因子白细胞介素平和升高抑炎细胞因子白细胞介素1β、白细胞介素6水10水平。目的:观察龙鳖胶囊对膝骨关节炎软骨细胞p38MAPK信号通路及NF-κB p65的影响。方法:将60只SD大鼠随机分为5组,每组12只,模型组、低剂量组、中剂量组、高剂量组建立右侧膝骨关节炎大鼠模型,造模后第3天,低剂量组、中剂量组、高剂量组分别灌胃给予0.312 5,0.625,0.937 5 g/kg龙鳖胶囊,2次/d,连续4周;对照组不造模。灌胃2,4周后,取膝关节制成组织切片,免疫组织化学SP法检测软骨组织中MEK-3/6、p38、ATF2、NF-κB p65及其磷酸化产物P-MEK-3/6、P-p38、P-ATF2、P-NF-κB p65的表达。结果与结论:给药2,4周后,各组细胞均有MEK-3/6、p38、ATF2、NF-κB p65及其磷酸化产物PMEK-3/6、P-p38、P-ATF2、P-NF-κB p65阳性表达,模型组MEK-3/6、p38、ATF2、NF-κB p65及其磷酸化产物P-MEK-3/6、P-p38、P-ATF2、P-NF-κB p65阳性细胞百分比均高于对照组(P<0.01),低、中、高剂量组上述指标阳性细胞百分比均低于模型组(P<0.05)。结果表明,龙鳖胶囊可抑制MEK-3/6、p38、ATF2、NF-κB p65及其磷酸化产物P-MEK-3/6、P-p38、P-ATF2、P-NF-κB p65的过表达,抑制骨关节炎软骨细胞中p38MAPK和NF-κB信号通路活化,发挥减改善软骨退变、保护软骨的作用。
BACKGROUND： Previous studies found that Longbie Capsule can relieve knee joint swelling of rats with knee osteoarthritis, and decrease the serum levels of interleukin-1β, interleukin-6 and interleukin-10. OBJECTIVE： To observe the influence of Longbie Capsule on p38 MAPK pathway and nuclear factor-κB p65（NF-κB p65） in chondrocytes of osteoarthritis. METHODS： Sixty Sprague-Dawley rats were equivalently randomized into five groups, and the rat models of right knee osteoarthritis were established in model, low-dose, middle-dose and high-dose groups. Three days later, rats in the latter three groups were respectively treated with 0.312 5, 0.625, and 0.937 5 g/kg Longbie Capsule via gastric lavage, twice daily for 4 consecutive weeks; while those in the control group received no intervention. At 2 and 4 weeks after treatment, the rat right knee joint was removed and made into paraffin tissue sections, and the expressions of MEK-3/6, p38, activating transcription factor 2（ATF2）, NF-κBp65, and their phosphorylated products of P-MEK-3/6, P-p38, P-ATF2, P-NF-κB p65 in cartilage tissue were detected by immunohistochemistry streptavidin-perosidase method. RESULTS AND CONCLUSION： After 2 and 4 weeks of treatment, chondrocytes in each group could express MEK-3/6, p38, ATF2, NF-κB p65, P-MEK-3/6, P-p38, P-ATF2 and P-NF-κB p65, and the percentage of positive cells in the model group was significantly higher than that in the control group（P〈0.01）, and the treatment groups（P〈0.05）. These results indicate that Longbie Capsule cannot only inhibit the over expressions of MEK-3/6, p38, ATF2, NF-κB p65 and their phosphorylated products, but also inhibit the activation of p38 MAPKs and NF-κB signaling pathway in chondrocytes of osteoarthritis, which is beneficial for cartilage degeneration and protecting the cartilage.
出处
《中国组织工程研究》
CAS
北大核心
2016年第46期6868-6877,共10页
Chinese Journal of Tissue Engineering Research
基金
国家自然科学基金项目(81473698
81273781)
教育部高等学校博士点科研基金项目(20124425110004)
广东省科技计划项目(2011B031700027)
广东省财政厅项目([2014]157号)
广东省中医药管理局项目(20164020)
广东省中医院中医药科学技术研究专项(YK2013B2N19
YN2015MS15)~~
