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 Tenghuang Jiangu 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

    • 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  本研究选择2021年4月—2022年10月就诊于甘肃中医药大学附属医院门诊及住院的绝经后骨质疏松患者,随机分为对照组和观察组。对照组在健康教育的基础上,给予碳酸钙D3颗粒(每次1袋,每天1次)+给予骨化三醇胶囊(0.25 μg口服,每次1粒,每天2次)+利塞膦酸钠片(5 mg口服,每次1片,每天1次)+注射用鲑降钙素(50 IU肌注,每天1次)。观察组在对照组给药的基础上,给予藤黄健骨胶囊(口服,每次5粒,每天2次)。分别在治疗前、治疗6个月后评价2组患者中医证候总积分及中医证候疗效,ELISA测定2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  依据西医诊断标准,中医证型诊断标准和纳排标准,最终符合PMOP西医诊断标准、中医证型为肾虚血瘀型的患者为60例。治疗6个月后,2组患者的中医证候总积分较治疗前均下降(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,2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,2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:
      OBJECTIVE To investigate the clinical efficacy and Th17 cell differentiation mechanism of Tenghuang Jiangu capsule on postmenopausal osteoporosis(PMOP) with kidney deficiency and blood stasis.
      METHODS This study selected PMOP patients who visited the outpatient and inpatient departments in Affiliated Hospital of Gansu University of Chinese Medicine from April 2021 to October 2022, the PMOP patients were randomly divided into control group and monitoring group. 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, one tablet each time, once a day)+salmon calcitonin(50 IU intramuscular injection, once a day). Based on the control group, monitoring group was given Tenghuang Jiangu capsule(orally, 5 capsules each time, twice a day). Before and 6 months after treatment, traditional scale for determining traditional Chinese medicine(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 According to the diagnostic criteria of western medicine, the diagnostic criteria of TCM syndrome differentiation, and the inclusion and exclusion criteria, there were 60 patients who ultimately met the western medicine diagnostic criteria of PMOP and had a TCM syndrome type of kidney deficiency and blood stasis. Compared with before treatment, the total scores of TCM symptoms of both groups decreased after 6 months of treatment(P<0.01), and the scores monitoring group was significantly lower than those in control group(P<0.05). After 6 months of 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 Tenghuang Jiangu capsule can improve the symptoms of PMOP patients with kidney deficiency and blood stasis, which can 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.

       

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