桑色素对大鼠骨关节炎影响的实验研究
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摘要
目的观察桑色素对大鼠骨关节炎的影响,并探讨其作用机制。
方法体外实验中,采用体外培养大鼠软骨原代细胞,观察不同浓度桑色素对白介素1-β诱导的基质金属蛋白酶-3、-13(MMP-3, -13)及基质金属蛋白酶组织抑制因子-1(TIMP-1)表达的影响,同时研究桑色素对软骨细胞MAPK通路中ERK、p38和JNK的影响；体内实验中,15只SD大鼠行单侧前交叉韧带离断术,术后随机分为假手术组、实验组和对照组。实验组每日予桑色素悬液灌胃,剂量为50mg/kg/day,连续4周,处死后取膝关节行大体和组织病理学检查。
结果细胞实验显示桑色素能抑制白介素1-β诱导的MMP-3和MMP-13表达,同时上调TIMP-1水平,其机制可能是通过抑制ERK和p38通路的磷酸化。动物实验中组织病理学检查显示实验组软骨病变程度轻于对照组。
结论桑色素对大鼠关节软骨有保护作用,能抑制其分解代谢,延缓骨关节炎的进展。
Objective:Morin shows anti-oxidative, anti-carcinogenic and anti-inflammatory effects and may be useful in many clinical applications. The effects of morin on articular cartilage metabolism remain unknown, so this study was performed to evaluate these effects in vitro and in vivo.
Methods:For the in vitro work, rat articular chondrocytes were cultured in a monolayer and matrix metalloproteinase-3 (MMP-3),-13 and tissue inhibitor of metalloproteinase (TIMP-1) expression was evaluated by real-time quantitative PCR and western-blot. We also examined the effects of morin on MAPK phosphorylation. For the in vivo work, morin was orally administered to rats after anterior cruciate ligament transection (ACLT).
Results:Morin inhibited the expression of MMP-3,-13 and increased the expression of TIMP-1 in IL-1β-induced rat chondrocytes. In addition, morin inhibited IL-1β-induced phosphorylation of ERK and p38. The in vivo study in a rat model of OA showed that morin suppressed cartilage degradation.
Conclusions:These findings suggest that morin may play a protective role in the development of O A and may be useful in the treatment of OA.
方法体外实验中,采用体外培养大鼠软骨原代细胞,观察不同浓度桑色素对白介素1-β诱导的基质金属蛋白酶-3、-13(MMP-3, -13)及基质金属蛋白酶组织抑制因子-1(TIMP-1)表达的影响,同时研究桑色素对软骨细胞MAPK通路中ERK、p38和JNK的影响；体内实验中,15只SD大鼠行单侧前交叉韧带离断术,术后随机分为假手术组、实验组和对照组。实验组每日予桑色素悬液灌胃,剂量为50mg/kg/day,连续4周,处死后取膝关节行大体和组织病理学检查。
结果细胞实验显示桑色素能抑制白介素1-β诱导的MMP-3和MMP-13表达,同时上调TIMP-1水平,其机制可能是通过抑制ERK和p38通路的磷酸化。动物实验中组织病理学检查显示实验组软骨病变程度轻于对照组。
结论桑色素对大鼠关节软骨有保护作用,能抑制其分解代谢,延缓骨关节炎的进展。
Objective:Morin shows anti-oxidative, anti-carcinogenic and anti-inflammatory effects and may be useful in many clinical applications. The effects of morin on articular cartilage metabolism remain unknown, so this study was performed to evaluate these effects in vitro and in vivo.
Methods:For the in vitro work, rat articular chondrocytes were cultured in a monolayer and matrix metalloproteinase-3 (MMP-3),-13 and tissue inhibitor of metalloproteinase (TIMP-1) expression was evaluated by real-time quantitative PCR and western-blot. We also examined the effects of morin on MAPK phosphorylation. For the in vivo work, morin was orally administered to rats after anterior cruciate ligament transection (ACLT).
Results:Morin inhibited the expression of MMP-3,-13 and increased the expression of TIMP-1 in IL-1β-induced rat chondrocytes. In addition, morin inhibited IL-1β-induced phosphorylation of ERK and p38. The in vivo study in a rat model of OA showed that morin suppressed cartilage degradation.
Conclusions:These findings suggest that morin may play a protective role in the development of O A and may be useful in the treatment of OA.
引文
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