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1.河南中医药大学教务部,郑州 450046
2.河南中医药大学医学院,郑州 450046
3.河南中医药大学第五临床医学院,郑州 450002
4.河南中医药大学第二临床医学院,郑州 450002
5.河南中医药大学第三附属医院妇产科,郑州 450008
副教授,硕士生导师。研究方向:中医妇科学。电话:0371-86550201。E-mail:mary868@163.com
教授,博士生导师。研究方向:中医妇科学。电话:0371-86550201。E-mail:13938427612@126.com
收稿日期:2024-08-20,
修回日期:2024-12-02,
录用日期:2024-12-02,
纸质出版日期:2025-01-15
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马丽亚,吴星霏,吴刘俊,等.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[J].中国药房,2025,36(01):37-43.
MA Liya,WU Xingfei,WU Liujun,et al.Improvement mechanism of Pangshi antai zhixue decoction on spontaneous abortion with heat syndrome by regulating NLRP3 inflammasome[J].ZHONGGUO YAOFANG,2025,36(01):37-43.
马丽亚,吴星霏,吴刘俊,等.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[J].中国药房,2025,36(01):37-43. DOI: 10.6039/j.issn.1001-0408.2025.01.07.
MA Liya,WU Xingfei,WU Liujun,et al.Improvement mechanism of Pangshi antai zhixue decoction on spontaneous abortion with heat syndrome by regulating NLRP3 inflammasome[J].ZHONGGUO YAOFANG,2025,36(01):37-43. DOI: 10.6039/j.issn.1001-0408.2025.01.07.
目的
2
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
2
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1 d大鼠随机分为正常组、模型组、地屈孕酮组(0.002 g/kg)和庞氏安胎止血汤低、中、高剂量组(11.025、22.05、44.10 g/kg),每组10只。各组大鼠灌胃蒸馏水/相应药液,每天1次,连续12 d。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24 h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
2
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-5 kJ/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
2
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。
OBJECTIVE
2
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
2
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-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
2
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
2
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.
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