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静安口服液通过 NMDAR/MAPK/CREB 通路减轻抽动秽语综合征 和 。

Jing-an oral liquid alleviates Tourette syndrome via the NMDAR/MAPK/CREB pathway and .

机构信息

Department of Pediatrics, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, China.

Department of Pediatric, Nanjing University of Chinese Medicine, Nanjing, China.

出版信息

Pharm Biol. 2022 Dec;60(1):1790-1800. doi: 10.1080/13880209.2022.2116056.

Abstract

CONTEXT

Jing-an oral liquid (JA) is a Chinese herbal formula used in the treatment of Tourette syndrome (TS); however, its mechanism is unclear.

OBJECTIVE

To investigate the effects of JA on amino acid neurotransmitters and microglia activation and .

MATERIALS AND METHODS

Sixty male Sprague-Dawley rats were divided into a control group and 5 TS groups. TS was induced in rats with intraperitoneal injection of 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (1 mg/kg) and in BV2 cells with lipopolysaccharide. Control and model rats were administered saline, whereas treatment groups were administered JA (5.18, 10.36, or 20.72 g/kg) or tiapride (a benzamide, 23.5 mg/kg) by gavage once daily for 21 days. Stereotypic behaviour was tested. The levels of -methyl-d-aspartate receptor (NMDAR)/mitogen-activated protein kinase/cAMP response element-binding protein (CREB)-related proteins in striatum and BV2 cells were measured via western blots. CD11b and IBa1 levels were also measured. Ultra-high-performance liquid-chromatography was used to determine γ-aminobutyric acid (GABA), glutamic acid (Glu), and aspartic acid (ASP) levels.

RESULTS

JA markedly alleviated the stereotype behaviour (25.92 ± 0.35 to 13.78 ± 0.47) in rats. It also increased NMDAR1 (0.48 ± 0.09 to 0.67 ± 0.08; 0.54 ± 0.07 to 1.19 ± 0.18) expression and down-regulated the expression of p-ERK, p-JNK, p-P38, and p-CREB in BV2 cells and rat striatum. Additionally, Glu, ASP, GABA, CD11b, and IBa1 levels were significantly decreased by JA.

DISCUSSION AND CONCLUSIONS

JA suppressed microglia activation and regulated the levels of amino acid neurotransmitters, indicating that it could be a promising therapeutic agent for TS.

摘要

背景

静安口服液(JA)是一种用于治疗妥瑞氏综合征(TS)的中草药配方,但作用机制尚不清楚。

目的

探讨 JA 对氨基酸递质和小胶质细胞激活的影响。

材料和方法

60 只雄性 Sprague-Dawley 大鼠分为对照组和 5 个 TS 组。腹腔注射 1-(2,5-二甲氧基-4-碘苯基)-2-氨基丙烷(1mg/kg)和脂多糖诱导大鼠 TS,BV2 细胞诱导 TS。对照组和模型组给予生理盐水,治疗组给予 JA(5.18、10.36 或 20.72g/kg)或噻哌啶(苯甲酰胺,23.5mg/kg)灌胃,每日 1 次,共 21 天。测试刻板行为。通过 Western blot 测定纹状体和 BV2 细胞中 N-甲基-D-天冬氨酸受体(NMDAR)/丝裂原活化蛋白激酶/cAMP 反应元件结合蛋白(CREB)相关蛋白的水平。还测量了 CD11b 和 IBa1 水平。超高效液相色谱法用于测定γ-氨基丁酸(GABA)、谷氨酸(Glu)和天冬氨酸(ASP)水平。

结果

JA 显著减轻大鼠刻板行为(25.92±0.35 至 13.78±0.47)。它还增加了 NMDAR1(0.48±0.09 至 0.67±0.08;0.54±0.07 至 1.19±0.18)的表达,并下调了 BV2 细胞和大鼠纹状体中 p-ERK、p-JNK、p-P38 和 p-CREB 的表达。此外,JA 显著降低了 Glu、ASP、GABA、CD11b 和 IBa1 的水平。

讨论与结论

JA 抑制小胶质细胞激活并调节氨基酸递质水平,表明 JA 可能是治疗 TS 的一种有前途的治疗剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e317/9487928/43fef889e897/IPHB_A_2116056_F0001_C.jpg

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