| Objective:1.Perform visualized analysis of the keywords and other contents of the research on the treatment of hemorrhagic stroke with internal therapy of traditional Chinese medicine in China in the past 10 years,to provide references for the basic and clinical research of the treatment of hemorrhagic stroke with internal therapy of traditional Chinese medicine in the future.2.Apply the TCM inheritance auxiliary platform to do a retrospective study on the medical records of patients with acute cerebral hemorrhage,analyze the medication law and extract the core prescription,so as to provide experience and references for the treatment of acute cerebral hemorrhage.3.Clarify the mechanism of NCXP in improving the injury of cerebral hemorrhage model in vivo and in vitro and explore the effect of NCXP on ferroptosis,inflammatory reaction and oxidative stress injury.Methods:1.Taking CNKI as the data source,search the literature on the treatment of cerebral hemorrhage by TCM internal therapy from January 1st,2013 to December 31 st,2023.Save the effective search results in refworks format and import them into Cite Space6.2R4 software.2.Upload the medical record information(current symptoms,tongue and pulse,diagnosis,prescription,etc.)of patients with good prognosis in acute cerebral hemorrhage to the traditional Chinese Medicine Inheritance auxiliary platform(V3.0),and analyze it by clustering and other mining methods.3.In the first chapter,animal experiments used autologous blood injection to establish a rat model of cerebral hemorrhage,and cell experiments used Hemin to induce BV2 cells to establish an in vitro model of cerebral hemorrhage.Longa rating scale was used to evaluate the neurological function of rats with cerebral hemorrhage;The differences of brain tissue water content among the groups were compared;HE staining was used to observe the pathological changes of brain tissue in each group;ELISA,biochemical kit,RT-q PCR and other experimental methods were used to detect the oxidative stress and related inflammatory factors of intracerebral hemorrhage model in vivo and in vitro.In the second chapter,bioinformatics methods were applied to theoretically identify that cerebral hemorrhage can target ferroptosis for the treatment of cerebral hemorrhage,and screen the core genes and pathways.The contents of Fe2+ and ATP in brain tissues and cells were detected to determine the changes of iron accumulation and mitochondrial function.The expression of ferroptosis related proteins was detected by Western blot.Biochemical kit,ELISA and RT-q PCR were used to detect the inflammatory factors and oxidative stress indexes of cerebral hemorrhage model in vivo and in vitro.In the third chapter,the TLR4/My D88/p38 MAPK/TNF-αsignaling pathway and the expression of ferroptosis related proteins were detected by Western blot using the method of adding TLR4 pathway inhibitors.The detection of iron accumulation,mitochondrial function,inflammatory factors and oxidative stress indicators was the same as the second chapter.Results:1.A total of 377 literatures were included.In the past 10 years,the literature on the treatment of intracerebral hemorrhage with internal treatment of traditional Chinese medicine has showed,In the co-occurrence analysis of key words,cerebral hemorrhage,clinical efficacy,acute phase,promoting blood circulation and removing blood stasis,hypertension,traditional Chinese medicine,neurological function,breaking blood and removing blood stasis occurred most frequently.Key words such as inflammatory reaction,filling essence and marrow,stroke,neuroprotection,traditional Chinese medicine,activating blood circulation and removing blood stasis,cooling blood and activating blood stasis ranked high.The main directions of the hot topics that concerned by scholars in the field include: breaking blood and removing blood stasis,traditional Chinese medicine,curative effect,Panax notoginseng,clinical curative effect,medication law,neurological function,clinical effect,syndrome differentiation and treatment.In the past 10 years,the treatment time span of stasis removing drugs for cerebral hemorrhage and cerebral protection was long.According to the analysis of key words in the Chinese literatures,the heat duration of the treatment of cerebral hemorrhage with the method of breaking blood and removing blood stasis represented by Di Dang decoction is longer.2.There were 113 patients with good prognosis with 289 prescriptions,involving 186 drugs and a total frequency of 5183 times.In terms of gender,71 males and 42 females were included;In terms of age,the age of patients ranged from 31 to 86 years old,and the proportion of patients older than 60 years old(55 cases)was the largest;In terms of symptoms,the most frequent symptoms were dry stool,poor sleep,dry mouth and dizziness,etc.In terms of tongue diagnosis,the tongue was mainly red,dark and purple,and the tongue coating was white and yellow with more frequency;In terms of pulse diagnosis,the most frequent pulse signs were pulse string,pulse slippery,pulse sinking,and pulse number;In terms of syndrome elements,blood stasis occured most frequently,followed by fire,phlegm,dynamic wind,Qi deficiency and Yin deficiency.In this study,cold nature of drugs appeared the most frequently in the four natures of drugs,reaching 1742 times;Among the five flavor attributes,the five flavors that appear more frequently were bitter,sweet and pungent in turn;According to the statistics of meridian tropism,the more frequent meridians were liver meridians and stomach meridians.Kmeans algorithm and regression simulation were applied to cluster analysis,and the results showed that the commonly used prescriptions included Naochuxue Prescription,Banxia Baizhu Tianma Decoction and Dachaihu Decoction.3.NCXP can reduce the neurological damage,brain water content and pathological changes in rats with cerebral hemorrhage,improve the survival rate of BV2 cells induced by Hemin,down regulate the expression of pro-inflammatory factors such as TNF-α and IL-6 in vivo and in vitro models of cerebral hemorrhage,promote the expression of anti-inflammatory factors such as IL-10,inhibit the expression of MDA and promote the expression of oxidative stress indicators such as SOD,cat,GSH-Px;Bioinformatics analysis showed that the key genes of iron death targeted by Naochuxue prescription in the treatment of cerebral hemorrhage included TP53,AKT1,SRC,Jun and TNF,etc;The enriched pathways mainly involved tumor necrosis factor signaling pathway;NCXP can reduce Fe2+ content,promote ATP content,upregulate GPX4 and inhibit ACSL4 expression in rat model of cerebral hemorrhage and in vitro model of hemin induced cerebral hemorrhage,improve cell survival rate of in vitro model of cerebral hemorrhage by inhibiting iron death and reduce inflammatory reaction and oxidative stress damage in vitro model of cerebral hemorrhage;After the addition of TAK242,NCXP could inhibit the expression of TLR4,My D88,p38 MAPK,TNF-α and ACSL4,promote the expression of GPX4,inhibit the level of Fe2+ in the in vitro model of intracerebral hemorrhage,upregulate the content of ATP and inhibit the inflammatory response and oxidative stress injury level in vitro model of intracerebral hemorrhage.Conclusion:1.In the past 10 years,the research hotspots of research papers on the treatment of intracerebral hemorrhage by internal treatment of traditional Chinese medicine can be summarized by the analysis results of keywords as follows: Research on promoting blood circulation,breaking blood and removing blood stasis drugs in the treatment of cerebral hemorrhage to improve neurological function and brain protection based on inflammatory reaction and brain edema.2.Through drug mode analysis and core prescription analysis,we found that Naochuxue prescription was commonly used prescription for the treatment of acute intracerebral hemorrhage.3.NCXP can reduce the brain injury of cerebral hemorrhage model in vivo,improve the cell survival rate of cerebral hemorrhage model in vitro and inhibit the inflammatory reaction and oxidative stress injury of cerebral hemorrhage model in vivo and in vitro;NCXP can reduce iron ion deposition after cerebral hemorrhage injury,reduce iron death and play the role of iron death inhibitor to regulate the expression of iron death related proteins;NCXP can inhibit iron death by inhibiting TLR4/My D88/p38 MAPK/TNF-α signaling pathway to reduce the injury of cerebral hemorrhage model. |
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