Tokishakuyakusan, a Kampo medicine, attenuates endometriosis-like lesions and hyperalgesia in murine with endometriosis-like symptoms

Tokishakuyakusan, a Kampo medicine, attenuates endometriosis-like lesions and hyperalgesia in murine with endometriosis-like symptoms
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DOI:
10.1111/aji.13182
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发表时间:
2019-09-10
影响因子:
3.6
通讯作者:
Harada, Tasuku
Harada, Tasuku
中科院分区:
医学3区
文献类型:
--
作者:
Nagira, Kei;Taniguchi, Fuminori;Harada, Tasuku

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问题日本传统药物(汉方)Tokishakuyakusan(TSS)对小鼠子宫内膜异位症模型的影响如何?方法采用BALB/c小鼠建立小鼠子宫内膜异位症模型。将脂多糖(LPS)植入腹腔,建立同种异体子宫模型。我们口服了2周的TSS(1.0 g/kg)。处理完成后,我们对所有小鼠进行热板试验,并在处死前采集血样。然后,在腹腔中收获子宫内膜样病变和子宫。使用Bio-Screening Suspension Array System测定血清和囊液中几种细胞因子的浓度。IL-33定位通过免疫组织化学测定。实时荧光定量RT-PCR检测子宫内膜异位症样病变或在位内膜中炎性细胞因子的基因表达。结果TSS治疗14 d后,囊肿样囊肿数量和囊肿重量明显减少。在TSS处理的小鼠中,对热刺激的潜伏期延长。TSS治疗没有改变血清中炎性细胞因子的浓度。TSS的摄入降低了类囊肿病变中IL-33 mRNA的表达,并导致病变囊液中升高的IL-33合成有减弱的趋势。结论TSS可改善LPS致大鼠类神经纤维变性模型的痛敏和损伤形成。TSS是治疗子宫内膜异位症伴痛经患者的一个可能的理想靶点。
Problem How are the effects of Tokishakuyakusan (TSS), a traditional Japanese medicine (Kampo) on murine endometriosis model? Methods BALB/c mice were used for making the murine endometriosis model. Homogeneous uterus was surgically implanted with lipopolysaccharide (LPS) in peritoneal cavity. We administered 2 weeks of TSS (1.0 g/kg) orally. Upon treatment completion, we performed the hot plate test for all mice and collected blood samples before sacrifice. Then, the endometriosis-like lesions and uteri in the abdominal cavity were harvested. Concentrations of several cytokines in sera and cyst fluids were measured using Bio-Plex Suspension Array System. IL-33 localization was determined by immunohistochemistry. Gene expression of inflammatory cytokines in the endometriosis-like lesions or the eutopic endometrium was evaluated by real-time RT-PCR. Results After 14 days of TSS treatment, the numbers of endometriosis-like cysts and cyst weight were significantly decreased. In TSS-treated mice, the latency against heat stimuli was extended. Inflammatory cytokine concentrations in sera were not changed by TSS treatment. TSS intake decreased IL-33 mRNA expression in endometriosis-like lesions and led to the tendency of attenuation of the elevated IL-33 synthesis in the cyst fluids of lesions. Conclusion These results suggest the TSS ameliorated the hyperalgesia and lesion formation on the LPS-accelerated endometriosis-like model. TSS represents a possible ideal target of novel therapeutics for endometriosis patients with dysmenorrhea.