川芎嗪对膝骨性关节炎大鼠软骨下骨中miR-20b/VEGF和BMP2/Smad1通路的影响-中国药房

川芎嗪对膝骨性关节炎大鼠软骨下骨中miR-20b/VEGF和BMP2/Smad1通路的影响

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篇名：	川芎嗪对膝骨性关节炎大鼠软骨下骨中miR-20b/VEGF和BMP2/Smad1通路的影响
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摘要：	目的：研究川芎嗪对膝骨性关节炎（KOA）模型大鼠软骨下骨中微小核糖核酸miR-20b/血管内皮生长因子（VEGF）和骨形态发生蛋白2（BMP2）/Smad1通路的影响，并探讨川芎嗪防治KOA的作用机制。方法：取健康雄性SD大鼠18只，随机分为正常对照组、模型组、川芎嗪组，每组6只。对后两组大鼠通过膝关节腔注射4％木瓜蛋白酶溶液建立KOA模型。末次注射后第2天起，川芎嗪组大鼠灌胃川芎嗪混悬液（100 mg/kg）2 mL，正常对照组、模型组大鼠灌胃等体积生理盐水，每天1次，连续6周。给药结束后，暴露大鼠双侧膝关节软骨进行大体情况观察。截取大鼠膝关节，进行切片和苏木精-伊红（HE）染色，在显微镜下观察组织病理学变化，并采用改良的Mankin’s评分进行组织学评分。采用逆转录-聚合酶链反应（RT-PCR）法检测大鼠软骨下骨组织中VEGF、BMP2、Smad1的mRNA表达和miR-20b表达水平；采用Western Blot法检测VEGF、BMP2、Smad1的蛋白表达水平。结果：模型组和川芎嗪组大鼠的膝关节均出现不同程度的软骨损伤；与正常对照组比较，模型组大鼠膝关节软骨组织Mankin’s评分显著升高（P＜0.01）；软骨下骨组织中BMP、Smad1的mRNA和蛋白表达以及miR-20b表达水平均显著降低，VEGF的mRNA和蛋白表达水平均显著升高（P＜0.01）。与模型组比较，川芎嗪组大鼠关节软骨组织Mankin’s评分显著降低（P＜0.01）；软骨下骨组织中BMP、Smad1的mRNA和蛋白表达以及miR-20b表达水平均显著升高，VEGF的mRNA和蛋白表达水平均显著降低（P＜0.05或P＜0.01）。结论：川芎嗪能修复KOA模型大鼠损伤的关节软骨，其机制可能是通过上调软骨下骨中miR-20b表达水平，促进VEGF mRNA降解继而抑制VEGF蛋白的表达，同时激活BMP-2/Smad1信号通路而实现的。
ABSTRACT：	OBJECTIVE： To study the effects of ligustrazine on miR-20b/VEGF and BMP2/Smad1 pathways in subchondral bone of knee osteoarthritis （KOA） model rats， and to investigate the mechanism of ligustrazine for KOA prevention and treatment. METHODS： Totally 18 healthy male SD rats were randomly divided into normal control group， model group and ligustrazine group， with 6 rats in each group. The rats in the latter two groups were used to establish KOA model by intra-articular injection of 4％ papain solution. From the 2nd day after the last injection， ligustrazine group was given intragastrical administration of Ligustrazine suspension （100 mg/kg） 2 mL； normal control group and model group were given intragastrical administration of isometrical normal saline， once a day， for consecutive 6 weeks. After the last after medication， the situation of bilateral knee articular cartilage of rats were observed after exposure. The knee joints of rats were sectioned and stained with HE. The pathological change of articular cartilage were observed by microscope and scored by modified Mankin’s score. mRNA expression of VEGF， BMP2 and Smad1， and the expression of miR-20b were detected by RT-PCR； the protein expression of VEGF， BMP2 and Smad1 were detected by Western blot assay. RESULTS： Model group and ligustrazine group suffered from cartilage injury of knee joint at varying degrees. Compared with normal control group， Mankin’s scores of knee joint and cartilage tissue were increased significantly in model group （P＜0.01）； mRNA and protein expression of BMP and Smad1， the expression of miR-20b in subchondral bone of model group were decreased significantly， while mRNA and protein expression of VEGF were increased significantly （P＜0.01）. Compared with model group， Mankin’s score of cartilage tissue were decreased significantly in ligustrazine group （P＜0.01）； mRNA and protein expression of BMP and Smad1， the expression of miR-20b in subchondral bone were increased significantly， while mRNA and protein expression of VEGF were decreased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS： Ligustrazine can repair damaged articular cartilage in KOA model rats， the mechanism of which may be associated with inhibiting the protein expression of VEGF and activating BMP-2/Smad1 signaling pathway via up-regulating the expression of miR-20b， and promoting the degradation of VEGF mRNA in subchondral bone.
期刊：	2019年第30卷第4期
作者：	梁桂洪，梁祖建，谢平金，潘建科，曾令烽，杨伟毅，黄和涛，韩燕鸿，刘军
AUTHORS：	LIANG Guihong，LIANG Zujian，XIE Pingjin，PAN Jianke，ZENG Lingfeng，YANG Weiyi，HUANG Hetao，HAN Yanhong，LIU Jun
关键字：	川芎嗪；膝骨性关节炎；软骨下骨；大鼠；miR-20b；血管内皮生长因子；骨形态发生蛋白；Smad；作用机制
KEYWORDS：	Ligustrazine； Knee osteoarthritis； Subchondral bone； Rat； miR-20b； VEGF； BMP； Smad； Mechanism
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