摘要
目的:从RANKL/RANK/OPG系统探讨补肾法抑制恶性肿瘤骨转移的作用机制。方法:在C57BL/6雄性小鼠左后肢接种Lewis肺癌细胞株制备肺癌骨转移动物模型,并将18只造模小鼠随机分为6组:模型对照组,补肾方低剂量组,补肾方中剂量组,补肾方高剂量组,唑来膦酸盐组以及补肾方(低)+唑来膦酸盐组。观察小鼠骨肿瘤组织病理,骨组织骨护素(OPG)、核因子κB受体活化因子配体(RANKL)、白介素-6(IL-6)蛋白的表达情况。结果:模型组小鼠病理图片显示:骨皮质表面大部分被肿瘤细胞侵蚀破坏,骨髓腔内骨小梁被严重破坏,骨髓腔内造血细胞部分坏死,结构模糊不清(+++);唑来膦酸组及补肾方中剂量、补肾方(低)+唑来膦酸盐组小鼠病理:骨皮质完整结构清晰,骨髓腔内骨小梁与造血细胞少量破坏(+);模型组转移癌OPG的表达较低,补肾方中剂量及补肾方(低)+唑来膦酸盐的OPG蛋白的表达增高,与模型组相比差异有统计学意义(P<0.05);补肾方低剂量、补肾方高剂量、唑来膦酸盐的OPG蛋白的表达与模型组相比差异无统计学意义(P>0.05);模型组转移癌RANKL的表达较高,补肾方高剂量的RANKL蛋白的表达降低,与模型组相比差异有统计学意义(P<0.01,)补肾方中剂量、唑来膦酸盐及补肾方(低)+唑来膦酸盐的RANKL蛋白的表达降低,与模型组相比差异有统计学意义(P<0.05),补肾方低剂量的RANKL蛋白的表达与模型组相比差异无统计学意义(P>0.05);模型组转移癌IL-6的表达较高,补肾方中剂量、补肾方高剂量的IL-6蛋白的表达降低,与模型组相比差异有统计学意义(P<0.01),唑来膦酸盐及补肾方(低)+唑来膦酸盐的IL-6蛋白的表达降低,与模型组相比差异有统计学意义(P<0.05),补肾方低剂量的IL-6蛋白的表达与模型组相比差异无统计学意义(P>0.05)。结论:补肾方可能通过增加OPG蛋白的表达,从而抑制破骨细胞活性,抑制肺腺癌细胞的骨转移;同
Objective:To explore the mechanism of kidney tonifying therapy in inhibiting bone metastasis of malignant tumor from RANKL/RANK/OPG system.Methods:Lewis lung cancer cell line was inoculated into the left hind limb of C57 BL/6 male mice to prepare the animal model of lung cancer bone metastasis.18 mice were randomly divided into 6 groups:model control group,low dose group,middle dose group,high dose group,zoledronic acid group and low+zoledronic acid group.The expression of osteoprotegerin(OPG),receptor activator of NF-κB living(RANKL),interleukin-6(IL-6)protein were observed.Results:Pathological pictures of model group mices showed that most of the surface of bone cortex were eroded and destroyed by tumor cells,bone trabeculas in marrow cavity were seriously damaged,and hematopoietic cells in marrow cavity were partially necrotic,and the structures were unclear(+++);pathology of zoledronic acid group and Bushen formula middle dose,Bushen formula(low)+zoledronic acid salt group(middle+West)mice:complete structures of bone cortex were clear,bone trabecula in marrow cavity and in the model group,the expression of OPG protein in the middle dose of Bushen group and Bushen formula(low)+zoledronic acid salt were significantly higher than that in the model group(P<0.05).The expression of OPG protein in the low dose of Bushen formula,the high dose of Bushen group and zoledronic acid salt were not significantly different from that in the model group(P>0.05).The expression of RANKL protein in the kidney tonifying group was significantly lower than that in the model group(P<0.01).There was no significant difference(P>0.05).The expression of IL-6 in the model group was higher than that in the model group,and the expression of IL-6 protein in the middle dose of kidney tonifying group and the high dose of kidney tonifying group was lower than that in the model group(P<0.01).The expression of IL-6 protein in zoledronic acid salt and kidney tonifying formula(low)+zoledronic acid salt was lower than that in the model group(P<0.05
作者
张士强
吴婷婷
李芸
周张杰
杨蕴
蒋海燕
夏晓婷
钟薏
ZHANG Shiqiang;WU Tingting;LI Yun;ZHOU Zhangjie;YANG Yun;JIANG Haiyan;XIA Xiaoting;ZHONG Yi(Yueyang Clinical School of Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Department of Oncology,Shanghai Integrated Hospital of Traditional Chinese and Western Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai 200082,China)
出处
《中国中医骨伤科杂志》
CAS
2021年第2期10-14,共5页
Chinese Journal of Traditional Medical Traumatology & Orthopedics
基金
上海市卫生和计划生育委员会科研课题(20154Y0092)
上海中医药大学高峰高原学科(临床人才专项)(2018ZYD001)
虹口区“国医强优”三年行动计划(HGY-KY-2018-34)。