庞氏安胎止血汤通过调控NLRP3炎症小体改善热证自然流产的作用机制-中国药房

庞氏安胎止血汤通过调控NLRP3炎症小体改善热证自然流产的作用机制

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篇名：	庞氏安胎止血汤通过调控NLRP3炎症小体改善热证自然流产的作用机制
TITLE：	Improvement mechanism of Pangshi antai zhixue decoction on spontaneous abortion with heat syndrome by regulating NLRP3 inflammasome
摘要：	目的研究庞氏安胎止血汤通过调控NOD样受体蛋白3（NLRP3）炎症小体改善热证自然流产的作用机制。方法采用分子对接技术预测庞氏安胎止血汤中13种主要活性成分与NLRP3、凋亡相关斑点样蛋白质（ASC）、胱天蛋白酶1前体（pro-caspase-1）的结合活性。将60只孕1d大鼠随机分为正常组、模型组、地屈孕酮组（0.002g/kg）和庞氏安胎止血汤低、中、高剂量组（11.025、22.05、44.10g/kg），每组10只。各组大鼠灌胃蒸馏水/相应药液，每天1次，连续12d。除正常组外，其余各组大鼠采用温阳中药和米非司酮诱导热证自然流产模型。末次给药24h后，检测大鼠血清中三碘甲状腺原氨酸（T3）、甲状腺素（T4）、白细胞介素2（IL-2）、IL-4、IL-6、IL-10、γ干扰素（IFN-γ）水平；计算流产率及子宫系数；观察大鼠妊娠子宫病理形态；检测妊娠子宫中NLRP3、ASC、caspase-1蛋白表达水平。结果分子对接结果显示，庞氏安胎止血汤13种主要活性成分与NLRP3、ASC、pro-caspase-1蛋白的结合能均小于－5kJ/mol。动物实验结果显示，与正常组比较，模型组大鼠子宫系数和血清中IL-4、IL-6、IL-10水平均显著降低（P＜0.05），流产率和血清中T3、T4、IL-2、IFN-γ水平以及妊娠子宫中NLRP3、ASC、caspase-1蛋白表达水平均显著升高（P＜0.05），妊娠子宫内膜存在流产病变；与模型组比较，庞氏安胎止血汤各剂量组大鼠上述大部分定量指标均显著逆转（P＜0.05），妊娠子宫内膜流产病变均有不同程度改善。结论庞氏安胎止血汤可能通过调节NLRP3炎症小体形成，下调IFN-γ、IL-2等促炎因子，上调IL-4、IL-6、IL-10等抑炎因子，从而影响母胎之间的免疫平衡，进而发挥改善热证自然流产的作用。
ABSTRACT：	OBJECTIVE To investigate the mechanism of Pangshi antai zhixue decoction in the improvement of spontaneous abortion with heat syndrome by regulating the NOD-like receptor protein 3 （NLRP3） inflammasome. METHODS The binding activities of 13 main components in Pangshi antai zhixue decoction with NLRP3， apoptosis-associated speck-like protein ， containing a CARD （ASC）， and caspase-1 precursor （pro- No.20-21ZY1053） caspase-1） were predicted by molecular docking. Sixty 1-day-old pregnant rats were randomly divided into normal group， model group， dexamethasone group （0.002 g/kg）， and Pangshi antai zhixue decoction low-， medium-， and high-dose groups （11.025， 22.05， 44.10 g/kg）， with 10 rats in each group. Each group was given distilled water/corresponding medicinal solution intragastrically， once a day， for 12 consecutive days. Except for normal group， other groups were given traditional Chinese medicine for warming yang and mifepristone to establish a model of spontaneous abortion with heat syndrome. 24 h after the last medication， serum levels of triiodothyronine （T3）， thyroxine （T4）， interleukin-2 （IL-2）， IL-4， IL-6， IL-10， and interferon-γ （IFN-γ） were all detected； the abortion rate and uterine coefficient were calculated； the pathological morphology of the pregnant uterus was observed； protein expressions of NLRP3， ASC and caspase-1 were detected. RESULTS The molecular docking results showed that the binding energies of 13 main components of Pangshi antai zhixue decoction with NLRP3， ASC， and pro-caspase-1 were all less than －5 kJ/moL. The animal experiment results showed that compared with normal group， the uterine coefficient and serum levels of IL-4， IL-6 and IL-10 were decreased significantly in model group （P＜0.05）； the abortion rate and serum levels of T3， T4， IL-2 and IFN-γ as well as protein expressions of NLRP3， ASC and caspase-1 were increased significantly （P＜0.05）； there were abortion lesions in the pregnant endometrium. Compared with the model group， most of the quantitative indicators mentioned above were significantly reversed in Pangshi antai zhixue decoction groups （P＜0.05）， and the endometrial miscarriage lesions in pregnancy were improved to varying degrees. CONCLUSIONS Pangshi antai zhixue decoction influences the immune balance between mother and fetus by regulating the formation of NLRP3 inflammasome， down-regulating pro-inflammatory cytokines such as IFN-γ and IL-2， and up-regulating anti-inflammatory cytokines such as IL-4， IL-6 and IL-10， thereby improving spontaneous abortion with heat syndrome.
期刊：	2025年第36卷第01期
作者：	马丽亚；吴星霏；吴刘俊；申艳朵；谢秉恒；张家乐；郝锦浩；于梦；中山裕美子；张明昊；张大伟
AUTHORS：	MA Liya，WU Xingfei，WU Liujun，SHEN Yanduo， XIE Bingheng，ZHANG Jiale，HAO Jinhao，YU Meng，NAKAYAMA Yumiko，ZHANG Minghao，ZHANG Dawei
关键字：	庞氏安胎止血汤；热证；自然流产；NOD样受体蛋白3；免疫平衡
KEYWORDS：	Pangshi antai zhixue decoction； heat syndrome； spontaneous abortion； NOD-like receptor protein 3； immune
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