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Mecanismo molecular de la regulación de la expresión de GPNMB por Liuwei Dihuang Wan para mejorar la autofagia en el tratamiento de la enfermedad de Alzheimer

  • role： First author第一作者
  • Affiliation：

    College of Basic Medicine， Liaoning University of Traditional Chinese Medicine（TCM）， Shenyang 110847，China

  • Email：751107629@qq.com
  • Introduction：刘羽茜，博士，讲师，从事中医药防治代谢性疾病分子机制研究，E-mail：751107629@qq.com
LIU Yuxi1,  
  • Affiliation：

    College of Basic Medicine， Liaoning University of Traditional Chinese Medicine（TCM）， Shenyang 110847，China

ZHU Zhongkang1,  
  • Affiliation：

    College of Basic Medicine， Liaoning University of Traditional Chinese Medicine（TCM）， Shenyang 110847，China

WANG Songnan1,  
  • Affiliation：

    College of Basic Medicine， Liaoning University of Traditional Chinese Medicine（TCM）， Shenyang 110847，China

LIU Jiali1,  
  • Affiliation：

    First Affiliated Hospital of Liaoning University of TCM， Shenyang 110847，China

YIN Ye2,  
  • Affiliation：

    College of Basic Medicine， Liaoning University of Traditional Chinese Medicine（TCM）， Shenyang 110847，China

MIAO Jiarui1,  
  • Affiliation：

    Teaching and Experimental Center，Liaoning University of TCM，Shenyang 110847，China

HE Shunuo3,  
  • role： Corresponding author通信作者
  • Affiliation：

    College of Basic Medicine， Liaoning University of Traditional Chinese Medicine（TCM）， Shenyang 110847，China

  • Email：danyu1978@163.com
  • Introduction：赵丹玉，博士，教授，从事中医药防治代谢性疾病分子机制研究，E-mail：danyu1978@163.com
ZHAO Danyu1*

resumen

El objetivo de este estudio fue investigar cómo Liuwei Dihuang Wan afecta la función de autofagia en el hipocampo de ratones de envejecimiento rápido (SAMP8) regulando la expresión de la glicoproteína B de melanoma no migratorio (GPNMB), y explorar el mecanismo de acción del tratamiento con el método de tonificar el riñón y llenar la esencia en la enfermedad de Alzheimer (AD). Métodos: En el primer experimento, 24 ratones SAMP8 de 5 meses fueron divididos aleatoriamente en grupo modelo y grupos de Liuwei Dihuang Wan con dosis baja, media y alta (0,59, 1,18, 2,36 g/kg). Se utilizaron 6 ratones SAMR1 de la misma edad como grupo normal. La capacidad de aprendizaje y memoria se evaluó mediante la prueba de reconocimiento de objetos nuevos, se midieron los niveles séricos de cortisol (Cort), hormona adrenocorticotrópica (ACTH) y 17-hidroxicorticosteroides urinarios (17-OHCS) mediante ELISA, se observaron las ultraestructuras neuronales del hipocampo mediante microscopía electrónica de transmisión y se detectó la expresión de proteínas GPNMB, ADAM10 y relacionadas con la autofagia mediante Western blot. En el segundo experimento, 18 ratones SAMP8 se dividieron en grupo modelo, grupo vector (Vector) y grupo de sobreexpresión de GPNMB (GPNMB^OE) mediante inyección estereotáxica de lentivirus (2 μL/lado), con detección posterior de expresión proteica por Western blot. En el tercero, 24 ratones SAMP8 se dividieron en grupo modelo, grupo Liuwei Dihuang Wan, grupo Liuwei Dihuang Wan+control negativo (NC) y grupo Liuwei Dihuang Wan+silenciamiento de GPNMB (shGPNMB), con inyección previa de virus lentiviral negativo o silenciamiento antes del tratamiento y detección posterior. Resultados: En comparación con el grupo normal, el índice de reconocimiento de objetos nuevos disminuyó significativamente en el grupo modelo (P<0.01); en comparación con el modelo, los índices aumentaron significativamente en los grupos de dosis media y alta (P<0.01); la microscopía electrónica mostró acumulación de autofagolisosomas en el hipocampo normal; el grupo modelo no mostró autofagosomas típicos y predominaban mitocondrias; las dosis baja y media mostraron pocos autofagolisosomas y autofagosomas de membrana doble; la dosis alta mostró un número mayor; ELISA y Western blot indicaron que el grupo modelo tenía niveles séricos elevados de Cort, ACTH y 17-OHCS, expresiones reducidas de ADAM10, Beclin1, LC3 II/I y aumentos de GPNMB y p62 (P<0.05, P<0.01); en comparación con el modelo, las dosis de Liuwei Dihuang Wan redujeron significativamente Cort y ACTH, sólo la dosis alta redujo 17-OHCS, además aumentaron significativamente GPNMB, ADAM10, Beclin1 y LC3 II/I, y disminuyeron p62 (P<0.01); GPNMB^OE aumentó la expresión de estas proteínas y disminuyó p62 (P<0.01); Liuwei Dihuang Wan incrementó la expresión proteica y Liuwei Dihuang Wan+shGPNMB la disminuyó, incrementando p62 (P<0.01). Conclusión: Liuwei Dihuang Wan puede mejorar la función de autofagia en el hipocampo aumentando la expresión de GPNMB, mejorando la enfermedad de Alzheimer.

palabra clave

enfermedad de Alzheimer; Liuwei Dihuang Wan; glicoproteína de melanoma no migratorio B (GPNMB); autofagia; tonificar el riñón y llenar la esencia

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