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[艾灸通过抑制NLRP3/焦亡轴上调miR-223-3p促进薄型子宫内膜大鼠的子宫内膜修复]

[Moxibustion promotes endometrial repair in rats with thin endometrium by inhibiting the NLRP3/pyroptosis axis upregulating miR-223-3p].

作者信息

Zhou Haiyi, He Siyi, Han Ruifang, Guan Yongge, Dong Lijuan, Song Yang

机构信息

School of Nursing, 2Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou 510000, China.

Department of Gynecology, Third Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510000, China.

出版信息

Nan Fang Yi Ke Da Xue Xue Bao. 2025 Jul 20;45(7):1380-1388. doi: 10.12122/j.issn.1673-4254.2025.07.04.

Abstract

OBJECTIVES

To explore the mechanism through which moxibustion promotes endometrial repair in rats with in thin endometrium (TE).

METHODS

Female SD rats were randomized into control group, 95% anhydrous ethanol-induced TE model group and moxibustion (at "Guan Yuan") group. High-throughput sequencing was used to identify the target genes of TE, and the targeting relationship between miR-223-3p and NLRP3 was verified using a dual luciferase assay. Histopathological of rat uterus was observed with HE staining, and expressions of miR-223-3p and NLRP3 were detected using RT-qPCR; serum levels of IL-1β and IL-18 of the rats were detected using ELISA, and protein expressions of NLRP3, ASC, caspase-1 and GSDMD in the uterus were detected with Western blotting. The pregnancies of the rats after treatment were counted.

RESULTS

Enrichment analysis of the differential genes suggested up-regulated inflammatory response in TE, and dual luciferase assay verified targeted inhibition of NLRP3 expression by miR-223-3p. The rat models of TE had significantly decreased endometrial thickness and reduced endometrial glands and blood vessels with enhanced mRNA expression of NLRP3, increased serum levels of IL-1β and IL-18, up-regulated protein expressions of NLRP3, ASC, caspase-1 and GSDMD, lowered pregnancy rates on both the affected and unaffected sides and the overall number of pregnancies. Treatment of the rat models with mo-xibustion obviously increased the endometrial thickness and the density of glands and blood vessels, up-regulated miR-223-3p expression, lowered serum IL-1β and IL-18 levels and the protein expressions of NLRP3, ASC, caspase-1 and GSDMD, and significantly increased the number of pregnancies.

CONCLUSIONS

Moxibustion at "Guan Yuan" acupoint up-regulates the expression of miR-223-3p, which results in targeted inhibition of NLRP3 to suppress pyroptosis and promote endometrial repair in rat models of TE.

摘要

目的

探讨艾灸促进薄型子宫内膜(TE)大鼠子宫内膜修复的机制。

方法

将雌性SD大鼠随机分为对照组、95%无水乙醇诱导的TE模型组和艾灸(“关元”穴)组。采用高通量测序鉴定TE的靶基因,并用双荧光素酶报告基因检测法验证miR-223-3p与NLRP3之间的靶向关系。用HE染色观察大鼠子宫的组织病理学变化,用RT-qPCR检测miR-223-3p和NLRP3的表达;用ELISA检测大鼠血清IL-1β和IL-18水平,用Western blotting检测子宫中NLRP3、ASC、caspase-1和GSDMD的蛋白表达。统计治疗后大鼠的妊娠情况。

结果

差异基因的富集分析表明TE中炎症反应上调,双荧光素酶报告基因检测法验证了miR-223-3p对NLRP3表达的靶向抑制作用。TE大鼠模型的子宫内膜厚度显著降低,子宫内膜腺体和血管减少,NLRP3的mRNA表达增强,血清IL-1β和IL-18水平升高,NLRP3、ASC、caspase-1和GSDMD的蛋白表达上调,患侧和未患侧的妊娠率及总妊娠数降低。艾灸治疗大鼠模型明显增加了子宫内膜厚度以及腺体和血管密度,上调了miR-223-3p表达,降低了血清IL-1β和IL-18水平以及NLRP3、ASC、caspase-1和GSDMD的蛋白表达,并显著增加了妊娠数。

结论

艾灸“关元”穴上调miR- 223-3p的表达,从而靶向抑制NLRP3以抑制细胞焦亡,促进TE大鼠模型的子宫内膜修复。

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