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2025, 12, v.49 1851-1856
苗药有柄石韦中降血糖有效成分异绿原酸B的体内机制研究
基金项目(Foundation): 国家自然科学基金项目(82160773)
邮箱(Email): longyi621@gzy.edu.cn;
DOI:
摘要:

目的 探究苗药有柄石韦中异绿原酸B通过AGE-RAGE信号通路调控T2DM大鼠关键靶基因的体内降血糖机制。方法 通过分子对接筛选异绿原酸B与AGE-RAGE通路相关蛋白(JNK、P38、BAX、CASP3、RAGE、BCL2)的结合能力;采用STZ腹腔注射(45 mg/kg)联合高脂高糖饲料诱导T2DM大鼠模型,设正常组、模型组及异绿原酸B干预组。提取胰腺组织RNA,qRT-PCR检测靶基因(JNK、P38、BAX、CASP3、RAGE、BCL2)mRNA表达。结果 分子对接显示,异绿原酸B与JNK(-9.2 kcal/mol)、P38(-9.5 kcal/mol)结合能最强,与BAX、CASP3、RAGE结合能均<-7.0 kcal/mol。STZ给药后大鼠的空腹血糖值(FBG)≥11.1 mmol/L,T2DM大鼠模型建立成功;STZ诱导的T2DM模型组FBG显著高于正常组(P<0.01),异绿原酸B干预组FBG较模型组降低(P<0.01),证实其降糖效应。qRT-PCR显示,模型组JNK、P38、BAX、CASP3、RAGE mRNA表达较正常组显著升高,而BCL2 mRNA降低(P<0.01);异绿原酸B干预后,上述基因表达趋势逆转,但BCL2 mRNA升高(P<0.01)。结论 苗药有柄石韦中异绿原酸B是其降血糖的重要有效成分,通过调节关键基因JNK、P38、BAX、CASP3、RAGE阻断AGE-RAGE信号通路介导的胰岛细胞凋亡,达到降血糖作用。

Abstract:

Objective To investigate the hypoglycemic mechanism of Isochlorogenic Acid B from Pyrrosia petiolosa(a Miao medicine) through the AGE-RAGE signaling pathway by regulating key target genes in Type 2 Diabetes Mellitus(T2DM) rats. Methods Molecular docking was used to screen the binding affinity of Isochlorogenic Acid B with proteins related to the AGE-RAGE pathway(JNK, P38, BAX, CASP3, RAGE, BCL2). T2DM rat models were induced using intraperitoneal injection of STZ(45 mg/kg) combined with a high-fat and high-sugar diet. The study included a normal group, a model group, and an Isochlorogenic Acid B intervention group. Pancreatic tissue RNA was extracted, and qRT-PCR was performed to detect mRNA expression levels of target genes(JNK, P38, BAX, CASP3, RAGE, BCL2). Results Molecular docking showed that Isochlorogenic Acid B had the strongest binding energy with JNK(-9.2 kcal/mol) and P38(-9.5 kcal/mol), while its binding energies with BAX, CASP3, and RAGE were all less than-7.0 kcal/mol. After STZ administration, fasting blood glucose(FBG) levels in rats were ≥11.1 mmol/L, indicating successful establishment of the T2DM rat model. FBG levels in the STZ-induced T2DM model group were significantly higher than in the normal group(P<0.01). In the Isochlorogenic Acid B intervention group, FBG levels were lower compared to the model group(P<0.01), confirming its hypoglycemic effect. qRT-PCR results showed that mRNA expression levels of JNK, P38, BAX, CASP3, and RAGE in the model group were significantly higher than in the normal group, while BCL2 mRNA expression was lower(P<0.01). After Isochlorogenic Acid B intervention, these gene expression trends were reversed, but BCL2 mRNA expression increased(P<0.01). Conclusion Isochlorogenic Acid B from Pyrrosia petiolosa is an important effective component for lowering blood glucose, which regulates key genes such as JNK, P38, BAX, CASP3, and RAGE to block AGE-RAGE pathway-mediated pancreatic cell apoptosis, thereby achieving its hypoglycemic effect.

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基本信息:

中图分类号:R285.5

引用信息:

[1]王硕石,解成士,常姣,等.苗药有柄石韦中降血糖有效成分异绿原酸B的体内机制研究[J].贵州医药,2025,49(12):1851-1856.

基金信息:

国家自然科学基金项目(82160773)

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