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1.福建中医药大学 药学院,福州 350108
2.中国中医科学院 中药研究所,北京 100700
李佳豪,在读硕士,从事中药药理学研究,E-mail:lijiahao3695@163.com
朱春燕,博士,从事中药药理学研究,E-mail:xijiangyue3013@163.com
林娜,博士,研究员,从事中药药理学研究,E-mail:linna888@163.com
收稿日期:2021-02-07,
网络出版日期:2021-03-18,
纸质出版日期:2021-05-20
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李佳豪,田聪敏,池宏宇等.瘀血痹片通过抑制外周炎症缓解慢性炎性痛小鼠痛觉过敏及足肿胀[J].中国实验方剂学杂志,2021,27(10):31-37.
LI Jia-hao,TIAN Cong-min,CHI Hong-yu,et al.Experimental Study of Yuxuebi Tablets by Inhibiting Peripheral Inflammation to Relieve Hyperalgesia and Foot Swelling in Mice with Chronic Inflammatory Pain[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(10):31-37.
李佳豪,田聪敏,池宏宇等.瘀血痹片通过抑制外周炎症缓解慢性炎性痛小鼠痛觉过敏及足肿胀[J].中国实验方剂学杂志,2021,27(10):31-37. DOI: 10.13422/j.cnki.syfjx.20210806.
LI Jia-hao,TIAN Cong-min,CHI Hong-yu,et al.Experimental Study of Yuxuebi Tablets by Inhibiting Peripheral Inflammation to Relieve Hyperalgesia and Foot Swelling in Mice with Chronic Inflammatory Pain[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(10):31-37. DOI: 10.13422/j.cnki.syfjx.20210806.
目的
2
观察瘀血痹片对慢性炎性痛小鼠痛觉过敏及足肿胀的影响,并探索初步作用机制。
方法
2
使用完全弗氏佐剂(CFA)左侧足底注射建立小鼠慢性炎性痛模型,并分为模型组、阳性药布洛芬组(91 mg·kg
-1
)和瘀血痹片低、中、高剂量组(55,110,220 mg·kg
-1
),同时以假手术组作对照。造模后每日剂量等分为早晚2次灌胃给药瘀血痹片或布洛芬,共给药19 d。给药后第18天热板法检测小鼠热痛阈值,第19天标准Von Frey纤维针检测小鼠机械痛阈值,并对足肿胀度进行评分和拍照。液相悬浮芯片技术对炎症因子及受体等36种经典广谱炎症相关因子进行定量分析,生物信息学筛选核心靶点,进行酶联免疫吸附测定(ELISA)检测。
结果
2
与假手术组比较,模型组小鼠机械痛阈值、足肿胀评分显著升高(
P
<
0.01),热痛敏潜伏时间显著降低(
P
<
0.01),足部30种炎症因子的表达明显增加(
P
<
0.05);与模型组比较,瘀血痹片高剂量组可显著降低慢性炎性痛小鼠的机械痛阈值、足肿胀评分(
P
<
0.01),热痛敏潜伏时间明显升高(
P
<
0.05),足部30种炎症因子的表达明显降低(
P
<
0.05),其中肿瘤坏死因子-
α
(TNF-
α
),白细胞介素-6(IL-6),白细胞介素-17A(IL-17A),CC趋化因子配体2(CCL2)为筛选出的核心靶点,TNF-
α,
IL-17A,CCL2的表达显著降低(
P
<
0.01)。
结论
2
瘀血痹片具有缓解慢性炎性痛小鼠的痛觉过敏和足肿胀的作用,其机制可能与抑制外周TNF-
α,
IL-17A和CCL2等炎症因子的表达有关。
Objective
2
To observe the effect of Yuxuebi tablets on hyperalgesia and foot swelling in mice with chronic inflammatory pain, and to explore the preliminary mechanism of action.
Method
2
A mouse model of chronic inflammatory pain was established with left plantar injection of complete Freund's adjuvant (CFA). The mice were divided into model group, positive drug ibuprofen group (91 mg·kg
-1
), Yuxuebi tablets low, medium and high dose groups (55, 110, 220 mg·kg
-1
),with the sham operation group as the control. After successful modeling, the daily dose was divided into two doses in the morning and evening by gavage to give Yuxuebi tablets or ibuprofen to the stomach for a total of 19 days. On the 18
th
day after the administration, the thermal pain threshold was detected by the hot plate method. On the 19
th
day, the standard Von Frey fiber needle was used to detect the mechanical pain threshold of the mice, and the degree of foot swelling was scored and photographed. The liquid-phase suspension chip technology was used to quantitatively analyze 36 classic broad-spectrum inflammation-related factors like inflammatory factors and receptors. Bioinformatics were used to screen core targets and perform enzymelinked immunosorbent assay (ELISA) detection.
Result
2
Compared with the sham operation group, the mechanical pain threshold and foot swelling score of the model froup significantly increased (
P
<
0.01), the latent time of heat sensitivity significantly decreased(
P
<
0.01), the expressions of 30 inflammatory factors in the foot increased(
P
<
0.05). Compared with the model group, the high dose of Yuxuebi tablets significantly reduced the mechanical pain threshold and foot swelling score of mice with chronic inflammatory pain(
P
<
0.01), significantly increased the latent time of heat sensitivity(
P
<
0.05), and reduced the expressions of 30 inflammatory factors in the foot(
P
<
0.05), among which tumor necrosis factor-
α
(TNF-
α
), interleukin-6 (IL-6), interleukin-17A (IL-17A), and C-C chemokine ligand 2 (CCL2) were the core targets screened out, and the expressions of TNF-
α
, IL-17A, and CCL2 significantly decreased (
P
<
0.01).
Conclusion
2
Yuxuebi tablets can relieve hyperalgesia and foot swelling in mice with chronic inflammatory pain, and its mechanism may be related to the inhibition of the expressions of peripheral inflammatory factors such as TNF-
α
, IL-17A, and CCL2 .
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