OBJECTIVE Our previous studies demonstrated that various ingredients from the traditional Chinese medicine(TCM)for promoting blood circulation and removing blood stasis,as exemplified by cryptotanshinone and salvianol...OBJECTIVE Our previous studies demonstrated that various ingredients from the traditional Chinese medicine(TCM)for promoting blood circulation and removing blood stasis,as exemplified by cryptotanshinone and salvianolic acid B,exerted striking effects on modulating angiogenesis and vascular permeability,which suggests that they may be effective in treating vascular leak-driven diseases(e.g.tumor,cerebral cavernous malformation and diabetic retinopathy).However,the lack of reliable and advanced technologies and models sets up difficult hurdles for better understanding the role of TCM for promoting blood circulation and removing blood stasis.To this end,this study is to outline numerous cutting-edge platforms that can be utilized for exploring the function of TCM for promoting blood circulation and removing blood stasis in vascular leak-driven diseases.METHODS Two-photon laser scanning fluorescence microscopy was used to observe the interactions between neutrophils and blood vessels in a real-time manner.Dynamic flow system was employed to mimic the in vivo behaviors of neutrophils.RIP1-Tag5 spontaneous pancreatic cancer model was used to study the function of tumor blood vessels.CCM2ECKO(deletion of CCM2 in endothelial cells)mice were employed to establish the cerebral cavernous malformation(CCM)animal model.Micro-computed tomography(micro-CT)was utilized to assess the CCM lesion.Müller cell-knockout mouse model was used to study the progression of diabetic retinopathy.Vascular permeability in this model was assessed by fluorescein angiography.RESULTS The interactions between neutrophils and endothelial cells involve a series of complicated processes,including rolling,adhesion,intraluminal crawling and transmigration,which were all monitored in vivo by two-photon laser scanning fluorescence microscopy in a real-time manner.Dynamic flow system was capable of recapitulating the biological behaviors of neutrophils in vitro.Tumor vascular function in particular vascular perfusion could be assessed in the RIP1-Tag5 spontaneous pancreatic cancer model.In terms of CCM studies,specific deletion of CCM2 in endothelial cells resulted in the initiation of CCM lesion.The size and number of CCM lesions could be visualized and quantified by micro-CT.Furthermore,the Müller cell-knockout mouse model was able to precisely reflect the clinical symptoms of diabetic retinopathy.Vascular leak could be monitored at different time points using fluorescein angiography.CONCLUSION An array of high technologies and animal models can be used in investigating the occurrence and progression of multiple vascular leak-driven diseases.The pre-clinical and clinical studies of TCM for promoting blood circulation and removing blood stasis provide fundamental support for the application of the above-mentioned platforms,with the purpose of uncovering the scientific basis of TCM for promoting blood circulation and removing blood stasis.展开更多
目的“活血化瘀类中药”在防治骨质疏松症(osteoporosis,OP)的相关性研究上取得了一定的进展,但目前尚未有这方面的系统综述性文章报道。本文通过对该研究方向进行系统性综述,以期为“活血化瘀类中药”在基础以及临床防治OP方面提供新...目的“活血化瘀类中药”在防治骨质疏松症(osteoporosis,OP)的相关性研究上取得了一定的进展,但目前尚未有这方面的系统综述性文章报道。本文通过对该研究方向进行系统性综述,以期为“活血化瘀类中药”在基础以及临床防治OP方面提供新的思路和方向。方法通过知网、万方、Web of Science、Pubmed以“骨质疏松”“骨痿”“血瘀”“瘀血”“osteoprosis”“traditional medicine”以及活血化瘀类中药的中英文等为主题词,检索近五年来活血化瘀类中药与骨质疏松症防治相关方面的研究,最后筛选出符合要求的文献,进行综述。结果以“虚瘀”为核心的OP中医发病机制理论探讨、中药复方对血瘀型OP的防治以及活血化瘀类中药单体,通过现代相关生物分子通路和铁代谢机制,从抑制氧化应激、降低破骨细胞活性、促进成骨细胞分化、双向调节成骨细胞和破骨细胞这四个方向防治OP,是目前活血化瘀类中药防治骨质疏松症相关性研究的三大方向。结论目前活血化瘀类中药单体防治骨质疏松症的临床研究较少。后期对于“活血化瘀类中药单体”防治OP的研究可以与现代纳米材料或其他领域新材料相结合,发展新型药物载体,更新药物递送途径,实现药物最佳疗效的发挥,促进基础研究向临床研究转化。展开更多
文摘OBJECTIVE Our previous studies demonstrated that various ingredients from the traditional Chinese medicine(TCM)for promoting blood circulation and removing blood stasis,as exemplified by cryptotanshinone and salvianolic acid B,exerted striking effects on modulating angiogenesis and vascular permeability,which suggests that they may be effective in treating vascular leak-driven diseases(e.g.tumor,cerebral cavernous malformation and diabetic retinopathy).However,the lack of reliable and advanced technologies and models sets up difficult hurdles for better understanding the role of TCM for promoting blood circulation and removing blood stasis.To this end,this study is to outline numerous cutting-edge platforms that can be utilized for exploring the function of TCM for promoting blood circulation and removing blood stasis in vascular leak-driven diseases.METHODS Two-photon laser scanning fluorescence microscopy was used to observe the interactions between neutrophils and blood vessels in a real-time manner.Dynamic flow system was employed to mimic the in vivo behaviors of neutrophils.RIP1-Tag5 spontaneous pancreatic cancer model was used to study the function of tumor blood vessels.CCM2ECKO(deletion of CCM2 in endothelial cells)mice were employed to establish the cerebral cavernous malformation(CCM)animal model.Micro-computed tomography(micro-CT)was utilized to assess the CCM lesion.Müller cell-knockout mouse model was used to study the progression of diabetic retinopathy.Vascular permeability in this model was assessed by fluorescein angiography.RESULTS The interactions between neutrophils and endothelial cells involve a series of complicated processes,including rolling,adhesion,intraluminal crawling and transmigration,which were all monitored in vivo by two-photon laser scanning fluorescence microscopy in a real-time manner.Dynamic flow system was capable of recapitulating the biological behaviors of neutrophils in vitro.Tumor vascular function in particular vascular perfusion could be assessed in the RIP1-Tag5 spontaneous pancreatic cancer model.In terms of CCM studies,specific deletion of CCM2 in endothelial cells resulted in the initiation of CCM lesion.The size and number of CCM lesions could be visualized and quantified by micro-CT.Furthermore,the Müller cell-knockout mouse model was able to precisely reflect the clinical symptoms of diabetic retinopathy.Vascular leak could be monitored at different time points using fluorescein angiography.CONCLUSION An array of high technologies and animal models can be used in investigating the occurrence and progression of multiple vascular leak-driven diseases.The pre-clinical and clinical studies of TCM for promoting blood circulation and removing blood stasis provide fundamental support for the application of the above-mentioned platforms,with the purpose of uncovering the scientific basis of TCM for promoting blood circulation and removing blood stasis.
文摘目的“活血化瘀类中药”在防治骨质疏松症(osteoporosis,OP)的相关性研究上取得了一定的进展,但目前尚未有这方面的系统综述性文章报道。本文通过对该研究方向进行系统性综述,以期为“活血化瘀类中药”在基础以及临床防治OP方面提供新的思路和方向。方法通过知网、万方、Web of Science、Pubmed以“骨质疏松”“骨痿”“血瘀”“瘀血”“osteoprosis”“traditional medicine”以及活血化瘀类中药的中英文等为主题词,检索近五年来活血化瘀类中药与骨质疏松症防治相关方面的研究,最后筛选出符合要求的文献,进行综述。结果以“虚瘀”为核心的OP中医发病机制理论探讨、中药复方对血瘀型OP的防治以及活血化瘀类中药单体,通过现代相关生物分子通路和铁代谢机制,从抑制氧化应激、降低破骨细胞活性、促进成骨细胞分化、双向调节成骨细胞和破骨细胞这四个方向防治OP,是目前活血化瘀类中药防治骨质疏松症相关性研究的三大方向。结论目前活血化瘀类中药单体防治骨质疏松症的临床研究较少。后期对于“活血化瘀类中药单体”防治OP的研究可以与现代纳米材料或其他领域新材料相结合,发展新型药物载体,更新药物递送途径,实现药物最佳疗效的发挥,促进基础研究向临床研究转化。