| 毛梦珂,葛杭萍,项静静,等.炙马钱子胶囊抑制BIPN的临床疗效及基于lncRNA ZFAS1(XIST)活化FAK信号通路抑制神经炎症的机制[J].浙江中医药大学学报,2023,47(12):1495-1504. |
| 炙马钱子胶囊抑制BIPN的临床疗效及基于lncRNA ZFAS1(XIST)活化FAK信号通路抑制神经炎症的机制 |
| The Mechanism of BIPN Intervention by Strychnine Based on lncRNA ZFAS1(XIST)/FAK Signaling Pathway |
| DOI：10.16466/j.issn1005-5509.2023.12.021 |
| 中文关键词: 炙马钱子胶囊 周围神经病变 硼替佐米 lncRNA XIST miR-96-5P FN1 FAK 信号通路 |
| 英文关键词: prepared strychnine capsules peripheral neuropathy bortezomib lncRNA XIST miR-96-5P FN1 FAK signaling pathway |
| 基金项目:浙江省中医药管理局科研基金一般项目(2021ZB092) |
|
| 摘要点击次数: 1243 |
| 全文下载次数: 1032 |
| 中文摘要: |
| [目的] 评估炙马钱子胶囊医治硼替佐米相关性周围神经病(bortezomib induced peripheral neuropathy，BIPN)的有效性，初步探究其基于长链非编码RNA(long noncoding RNA，lncRNA)X失活特异性转录本(X inactive specific transcript，XIST)/锌指结构反义转录本1(ZNFX1 antisense RNA 1，ZFAS1)干预BIPN的机制。[方法] 通过前瞻性非随机对照的研究方法，共收集20例符合多发性骨髓瘤中西医诊断并接受硼替佐米(bortezomib，BTZ)治疗而且发生BIPN接受炙马钱子胶囊治疗的患者，与未接受马钱子治疗的患者进行中医症候积分、神经毒性评分、周围神经病变(peripheral neuropathy，PN)分级、部分周围神经传导速度的比较。通过自身对照，采集治疗组患者的外周血液样本，使用酶联免疫吸附试验(enzyme linked immunosorbent assay，ELISA)检测炎症相关因子表达。培养DRG 50B11细胞，通过细胞增殖毒性检测筛选马钱子最佳作用浓度和时间及BTZ最佳作用时间，随机分为正常对照组、BTZ组、马钱子+BTZ组，以实时荧光定量聚合酶链式反应(Real-time quantitative polymerase chain reaction，Real-time qPCR)检测炎症相关因子及细胞总RNA相关指标表达，分析差异性及相关性。[结果] 临床研究显示，与对照组比较，患者治疗后PN、中医证候积分、神经毒性评分降低，周围神经传导速度增加(P<0.05)，无明显不良反应。实验研究显示，与治疗前比较，白细胞介素-17(interleukin-17，IL-17)、IL-1β、IL-6、肿瘤坏死因子-α(tumor necrosis factor-α，TNF-α)、神经生长因子(nerve growth factor，NGF)、脑源性神经营养因子(brain-derived neurotrophic factor，BDNF)表达均降低(P<0.05)，且与时间存在显著负相关性(P?<0.01)。与BTZ组比较，马钱子+BTZ组IL-17、TNF-α、IL-1β、IL-6、NGF、BDNF、lncRNA XIST、纤维粘连蛋白1(fibronectin 1，FN1)、磷酸化局部黏着斑激酶(phospho-focal adhesion kinase，p-FAK)表达降低(P<0.05)，miR-96-5P、miR-1271-5P表达升高(P<0.05)，lncRNA ZFAS1表达量差异无统计学意义(P>0.05)；lncRNA XIST表达与IL-17、TNF-α、IL-1β、IL-6、NGF、BDNF、FN1、p-FAK表达显著正相关(P<0.01)，与miR-96-5P存在中等负相关性(P<0.05)，与miR-1271-5P存在极弱相关或无相关性(P?>0.05)。[结论] 炙马钱子胶囊在一定程度上可缓解BIPN且较为安全，其机制可能与调控lncRNA XIST，促进miR-96-5P/FN1表达，抑制p-FAK介导的神经炎症有关。 |
| 英文摘要: |
| [Objective] To assess the effectiveness of prepared strychnine in the treatment of bortezomib-induced peripheral neuropathy(BIPN) and explore the mechanism of intervention of BIPN based on long noncoding RNA(lncRNA) X inactivated specific transcript(XIST)/ZNFX1 antisense RNA 1(ZFAS1). [Methods] Twenty patients diagnosed as multiple myeloma who received bortezomib(BTZ) and developed BIPN and received strgchnine treatment were collected by prospective non-randomized controlled study method. The traditional Chinese medicine(TCM) symptom score， neurotoxicity score， peripheral neuropathy(PN) grade， and partial peripheral nerve conduction velocity were compared with patients who did not receive strychnine treatment. Using self-control， peripheral blood samples were collected from patients in the treatment group， and enzyme-linked immunosorbent assay(ELISA) was used to detect the expression of inflammation-related factors. DRG 50B11 cells were cultured and screened by cell counting kit-8(CCK-8) for the optimal acting concentration and time of strychnine and the optimal acting time of BTZ， and the cases were randomly divided into normal control group， BTZ group， and strychnine+BTZ group. Real-time quantitative polymerase chain reaction(Real-time qPCR) was used to detect the expression levels of inflammation-related factors and total RNA related indexes， and it analyzed the differences and correlations. [Results] The clinical study showed that compared with control group， PN， TCM syndrome scores and neurotoxicity score were decreased after treatment， while peripheral nerve conduction velocity was increased(P<0.05)， and there were no significant adverse effects. The experimental results showed that compared with those before treatment， the expression of interleukin-17(IL-17)， tumor necrosis factor-α(TNF-α)， IL-1β， IL-6， nerve growth factor(NGF) and brain-derived neurotrophic factor(BDNF) were reduced(P<0.05)， and there was a significant negative correlation with time(P<0.01). Compared with BTZ group， the expression levels of IL-17， TNF-α， IL-1β， IL-6， NGF， BDNF， the lncRNA XIST， fibronectin 1(FN1) and phospho-focal adhesion kinase(p-FAK) were decreased in strychnine+BTZ group(P<0.05)， while the expressions of miR-96-5P and miR-1271-5P increased(P<0.05)， without significant difference in the expression of lncRNA ZFAS1(P>0.05). lncRNA XIST expression levels were significantly positively correlated with the expressions of IL-17， TNF-α， IL-1β， IL-6， NGF， BDNF， FN1 and p-FAK(P<0.01)， but no moderate negative correlated with miR-96-5P(P<0.05)， or very weakly correlated or no correlated with miR-1271-5P(P>0.05). [Conclusion] Prepared strychnine capsule can alleviate BIPN to a certain extent and is relatively safe， and its mechanism may be related to the regulation of lncRNA XIST for promoting the expression of miR-96-5P/FN1 and inhibit p-FAK-mediated neuroinflammation. |
|
查看全文
查看/发表评论 下载PDF阅读器 |
| 关闭 |