藤黄健骨胶囊通过调控TNF-α/IL-6/JAK2/STAT3通路抑制肾虚血瘀型绝经后骨质疏松患者Th17细胞分化的机制研究

Mechanism of Tenghuangjiangu Capsule Inhibiting Th17 Cell Differentiation in Postmenopausal Osteoporosis Patients with Kidney Deficiency and Blood Stasis by Regulating TNF-α/ IL-6/JAK2/STAT3 Signal Pathway

关键词:  骨藤黄健骨胶囊  肾虚血瘀  绝经后骨质疏松  TNF-α/IL-6/JAK2/STAT3通路  Th17细胞分化

Key words:  tenghuangjiangu capsule  kidney deficiency and blood stasis  postmenopausal osteoporosis  TNF-α/IL-6/JAK2/STAT3 pathway  Th17 cell differentiation

摘要:

摘要：目的 探讨藤黄健骨胶囊治疗肾虚血瘀型绝经后骨质疏松患者的疗效及Th17细胞分化机制。方法 选择符合纳排标准的肾虚血瘀型绝经后骨质疏松患者60例，随机分为对照组和观察组，每组各30例。对照组在健康教育的基础上，给予碳酸钙D3颗粒（1袋/次，1次/d）+给予骨化三醇胶囊（0.25μg口服，1粒/次，2次/d）＋利塞膦酸钠片（5mg口服，1片/次，1次/d）＋注射用鲑降钙素（50iu肌注，1次/d）。观察组基于对照组给药的基础上，给予藤黄健骨胶囊（口服，5粒/次，2次/d）。分别在治疗前、治疗6个月后评价两组患者中医证候总积分及中医证候疗效，ELISA法测定两组患者TNF-α/IL-6/JAK2/ STAT3通路关键分子的表达变化和Th17细胞标记分子RoRγt、IL-17的表达变化。结果 治疗6个月后两组患者的中医证候总积分均下降（P<0.01），且观察组较对照组下降更明显（P<0.05）；治疗6个月后，对照组的总有效率为63.33%，观察组的总有效率为86.67%，且观察组疗效明显优于对照组（P<0.05）；治疗6个月后两组患者细胞因子IL-6、IL-6R、JAK2、STAT3、TNF-α的表达水平均显著下降，IL-33的表达水平均显著上升（P<0.05或P<0.01），且观察组JAK2、STAT3、TNF-α的表达水平相较于对照组下降更明显（P<0.05或P<0.01）；治疗6个月后两组患者Th17细胞标记分子RoRγt、IL-17的表达水平均显著下降（P<0.01），且观察组Th17细胞标记分子RoRγt、IL-17的表达水平相较于对照组下降更明显（P<0.05）。结论 藤黄健骨胶囊治疗肾虚血瘀型绝经后骨质疏松有效，能够显著改善患者中医证候总积分和提高中医证候疗效，其作用机制可能与TNF-α/IL-6/JAK2/STAT3通路的抑制有关，进而抑制其Th17细胞分化。

Abstract:

ABSTRACT: OBJECTIVE To investigate the clinical efficacy and Th17 cell differentiation mechanism of tenghuangjiangu capsule on postmenopausal osteoporosis (PMOP) with kidney deficiency and blood stasis. METHODS To 60 patients of PMOP with kidney deficiency and blood stasis were randomly divided into control group and monitoring group (each of 30 cases). On the basis of health education, the control group was given Calcium carbonate D3 particles (one bag each time, once a day)+(calcitriol capsule 0.25 μg orally, one capsule at a time, twice a day)+risedronate sodium tablets (5 mg orally, once a day)+salmon calcitonin (injection 50iu intramuscular injection, once a day). Based on the control group, monitoring group was given tenghuangjiangu capsule (5 capsules each time, twice a day). Before and 6 months after treatment, traditional scale for determining TCM syndromes scores, the efficacy of TCM symptom in two groups of patients were detected. Meanwhile, the key molecules expression of TNF-α/IL-6/ JAK2/STAT3 pathway in two groups of patients were detected by ELISA, the expression levels of RoRγt, IL-17 of Th17 cell marker molecule were also measured by ELISA. RESULTS The total scores of TCM symptoms of both groups decreased after the 6-month treatment(P<0.01), and the monitoring group was significantly lower than those in control group (P<0.01). After the 6-month treatment, the total effective rate of the control group was 63.33%, and the total effective rate of the monitoring group was 86.67%, and the curative effect of the monitoring group was significantly better than that in control group (P<0.05). After 6 months of treatment, the expression levels of IL-6, IL-6R, JAK2, STAT3, TNF-α were decreased, the expression levels of IL-33 were increased in both groups (P<0.05 or P<0.01), and the expression levels of JAK2, STAT3, TNF-α in the monitoring group were significantly decreased than those in control group (P<0.05 or P<0.01). After 6 months of treatment, the expression levels of RoRγt, IL-17 of Th17 cell marker molecule were decreased in both groups (P<0.01), and the expression levels of RoRγt, IL-17 of Th17 cell marker molecule in the monitoring group were significantly decreased than those in control group (P<0.05). CONCLUSION Tenghuangjiangu capsule can improve the symptoms of PMOP patients with kidney deficiency and blood stasis, which was could more effectively improve TCM syndrome scores the efficacy of TCM symptom. The mechanism may be related to the inhibition of TNF-α/ IL-6/JAK2/STAT3 pathway, so as to inhibit the TH17 cell differentiation of postmenopausal osteoporosis.