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藤黄健骨胶囊对PMOP大鼠RANKL/c-Fos/NFATc1通路的影响 |
The effect of Tenghuang Jiangu Capsule on the RANKL/c-Fos/NFATc1 pathway in PMOP rats |
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DOI:10.3969/j.issn.1006-7108.2024.02.002 |
中文关键词: 绝经后骨质疏松症 藤黄健骨胶囊 破骨分化 骨重塑 |
英文关键词:postmenopausal osteoporosis Tenghuang Jiangu capsule osteoclast differentiation bone remodeling |
基金项目:国家自然科学基金项目(82060872);甘肃省中医药管理局项目(GZKP-2023-39、GZKP-2023-63);兰州市卫生健康科技发展项目(2021004);兰州市科技计划项目资助(2022-3-22);甘肃省“双一流”科研重点项目(GSSYLXM-05) |
作者 | 单位 | 安方玉 颜春鲁* 柳颖 王霞霞 孙柏 汪春梅 常伟荣 宋佳眙 王玉洁 张捷 肖志攀 高鹏 | AN Fangyu,YAN Chunlu*, LIU Ying, WANG Xiaxia, SUN Bai, WANG Chunmei, CHANG Weirong, SONG Jiayi, WANG Yujie, ZHANG Jie, XIAO Zhipan, GAO Peng |
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中文摘要: |
目的 探讨免疫调节分子IL-33对绝经后骨质疏松症(postmenopausal osteoporosis,PMOP)模型鼠RANKL/c-Fos/NFATc1信号轴的调控作用及藤黄健骨胶囊(Tenghuang Jiangu capsule,TJC)的干预机制。方法 构建PMOP大鼠模型,设置假手术组、PMOP模型组、阳性对照组(0.09 mg/kg)和TJC高、中、低剂量组(0.36、0.18、0.09 g/kg),灌胃给药,每天1次,持续8周。从大鼠末次给药后体质量、骨密度(bone mineral density,BMD)及股骨组织微结构等方面评价TJC的疗效;通过ELISA分析TJC对大鼠血清免疫调节因子IL-33、IL-1、IL-31变化;运用qPCR和Western blotting分析TJC对大鼠股骨OPG、RANKL、RANK、c-Fos、NFATc1表达量的影响。结果 与假手术组相比,PMOP模型组大鼠的体质量、骨髓脂肪组织相对面积(relative area of bone marrow adipose tissue,BMAT),IL-1、IL-31变化,RANKL、RANK、c-Fos、NFATc1的表达均出现了明显升高的趋势,而BMD、IL-33变化、OPG的表达则出现了明显下降的趋势(P<0.01);与PMOP模型组相比,TJC高剂量组大鼠体质量出现显著下降趋势、IL-33变化出现显著升高趋势(P<0.01),TJC中、高剂量组大鼠BMAT、RANK的表达出现显著下降趋势、OPG的表达出现显著升高趋势(P<0.05或P<0.01),TJC各剂量组大鼠IL-1、IL-31变化,RANKL、c-Fos、NFATc1出现显著降低趋势,BMD出现显著增加趋势(P<0.05或P<0.01)。结论 TJC能够提高PMOP大鼠免疫调控分子IL-33含量,抑制免疫调控分子IL-1、IL-31含量和破骨细胞分化标志分子NFATc1的表达,其机制可能与RANKL/c-Fos/NFATc1抑制骨代谢通路密切相关。 |
英文摘要: |
Objective To explore regulation effects of immunomodulatory molecule IL-33 on RANKL/c-Fos/ NFATc1 signal axis in rats with postmenopausal osteoporosis (PMOP)and intervention mechanism of Tenghuang Jiangu capsule (TJC). Methods The rat’s PMOP model was performed by bilateralovariectomy method . The rats were divided into sham group, PMOP model group, positive control group (0.09 mg/kg), TJC high, middle and low dose group (0.36, 0.18, 0.09 g/kg). These groups were intragastric administration once a day for 8 weeks. The curative effect of TJC was evaluated including body mass after last administration,BMD, and bone micro architecture. And the levevls of immune regulatory factors IL-33, IL-1, and IL-31in rat serum was checked by ELISA, the expressions of OPG, RANKL, RANK, c-Fos, NFATc1 in rat thigh-bone was determined by qPCR and Western blotting. Results Compared with the sham group, the body mass, BMAT, the levels of IL-1, IL-31, the expression of TRANKL, RANK, c-Fos, NFATc1 in the PMOP model group have a significant increase trend, the content of BMD, the level of IL-33 and the expression of OPG appeared a significant decrease trend (P<0.01). Compared with the PMOP model group, the body mass appeared significantly decrease trend in the TJC high dose group, and the level of IL-33 has a increase trend (P<0.01). BMAT, the expression of RANK appeared significantly decrease trend in the TJC middle dose group and the TJC high dose group, the expression of OPG appeared significantly increase trend (P<0.05 or P<0.01). The levels of IL-1, IL-31, the expression of TRANKL, RANK, c-Fos, NFATc1 have a significant decrease trend in the TJC low dose group, the TJC middle dose group and the TJC high dose group, the BMD has a significant increase trend (P<0.05 or P<0.01). Conclusion TJC can significantly raise the concentration of IL-33 in PMOP model rats, decrease the concentration ofIL-1, IL-31, and inhibit the expression of osteoclast differentiation marker NFATc1. Its mechanism may be closely related to the inhibition of RANKL/c-Fos/NFATc1 bone metabolic pathway. |
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