续苓健骨颗粒治疗肾虚血瘀型绝经后骨质疏松症的疗效及转录机制研究
Clinical and transcriptome mechanism study of Xulingjiangu granule in the treatment of postmenopausal osteoporosis of kidney deficiency and blood stasis type
  
DOI:10.3969/j.issn.1006.7108.2022.04.016
中文关键词:  绝经后骨质疏松症  续苓健骨颗粒  肾虚血瘀证  转录组
英文关键词:postmenopausal osteoporosis  Xuling Jiangu granules  kidney deficiency and blood stasis  transcriptome
基金项目:国家自然科学基金项目(81873323);福建省公益类科研院所基本科研专项(2018R1035-4)
作者单位
谢丽华1 柴昊2 叶云金1 李生强1 黄景文1 陈娟1 陈玄1 陈赛楠1 葛继荣1* 1.福建省中医药科学院骨质疏松证候基因组学研究室福建 福州 350003 2.福建中医药大学福建 福州 350122 
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中文摘要:
      探讨续苓健骨颗粒治疗肾虚血瘀型绝经后骨质疏松症的临床疗效及转录组机制。方法 选取肾虚血瘀型绝经后骨质疏松症患者,随机分为续苓健骨颗粒试验组及骨化三醇对照组。观察两组中医证候积分、骨密度及安全性指标。取6例试验组患者治疗前、后的外周血进行转录组测序,另选6例健康组作为对照,筛选差异表达基因并行KEGG分析。结果 完成病例:试验组27例,对照组27例。试验组中医证候疗效总有效率为96.30 %,显著优于对照组的77.78 %(P?0.05)。治疗后两组中医证候积分、腰脊刺痛、下肢痿软等临床症状评分较治疗前均下降(P<0.05),但组间比较差异无统计学意义(P>0.05)。两组治疗前后骨密度比较差异无统计学意义(P>0.05),但均保持稳定或呈现上升趋势。两组均未出现严重不良反应。转录组测序:试验组治疗前、后有319个差异基因;试验组治疗前与健康组有598个差异基因,其中19个差异基因(包括FOSB、H4C2、RAMP3等)在治疗后其表达显著改变。KEGG分析结果表明,FOSB参与破骨细胞分化、IL-17信号通路。结论 续苓健骨颗粒治疗绝经后骨质疏松症,能够显著改善临床症状,中医证候疗效优于骨化三醇,其作用机制可能与FOSB、RAMP3、H4C2基因及FOSB参与的破骨细胞分化、IL-17信号通路相关。
英文摘要:
      Objective To investigate the clinical efficacy and transcriptome mechanism of Xuling Jiangu granule on postmenopausal osteoporosis(PMOP) with kidney deficiency and blood stasis. Methods Patients of PMOP with kidney deficiency and blood stasis were randomly divided into the experimental group (Xuling Jiangu granules) and the control group(calcitriol). TCM syndrome score, bone mineral density and safety indexes were observed. Transcriptome sequencing was performed on 6 subjects before and after, and 6 patients with normal BMD. Differentially expressed genes were screened and KEGG analysis was performed. Results 27 cases in the experimental group and 27 cases in the control group were completed in the study. The total effective rate in experimental group (96.3%) was significantly higher than those in control group (77.8%) (P<0.05). After treatment, the scores of TCM syndrome, Lumbago, leg weakness in both groups decreased (P<0.05). There was no significant difference in BMD between the two groups before and after treatment (P>0.05). There were no serious adverse reactions in the two groups. The results showed that 319 and 598 differentially expressed genes were identified between before-treatment and after-treatment groups, as well as the test group and the normal group . 19 differentially expressed genes were changed after treatment including FOSB, H4C2, RAMP3. KEGG analysis showed FOSB was involved in osteoclast differentiation and IL-17 signaling pathway. Conclusion Xuling Jiangu granules can improve the symptoms of PMOP patients, which TCM syndrome effect is superior to calcitriol. The mechanism may be related to FOSB, RAMP3, H4C2 genes and osteoclast differentiation and IL-17 signaling pathway involved in FOSB.
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