1.Study on the characteristics of Chinese medicine syndromes and its basic metabolites of spontaneously hypertensive rats
Qiuju ZHANG ; Yu WANG ; Bishi LING ; Meilong SI ; Haoxian MENG ; Mengyuan TIAN ; Ming ZHANG ; Nini LIAN ; Wanrong KANG ; Hua JIN
Acta Laboratorium Animalis Scientia Sinica 2025;33(1):44-53
Objective To investigate the characteristics of Chinese medicine syndromes and the possible metabolic substance basis of spontaneously hypertensive rat(SHR).Methods 10-week-old SPF SHR and WKY of the same strain were divided into SHR group and WKY group with 8 rats in each group.The general state,temperament,peripheral vascular filling,tongue characteristics,diet,water intake,urine and feces volume and characteristics,blood pressure,heart rate,respiratory rate,pain threshold,and open field behavior of SHR rats were observed and tested comprehensively to identify the possible syndrome types of Chinese medicine.At the same time,liquid chromatography tandem mass spectrometry was used to analyze non-targeted serum metabolites to preliminarily reveal the material basis of blood pressure elevation and Chinese medicine syndrome manifestations.Results Compared with WKY group,the scores of dark yellow hair color,irritable degree and peripheral capillary filling were higher in SHR group(P<0.0001).Red tongue color,dry tongue,little body fluid;24 h diet and water intake,urine volume and fecal volume were less(P<0.05),fecal water content was lower(P<0.001);systolic blood pressure(SBP),diastolic blood pressure(DBP),mean arterial pressure(MAP),heart rate(HR)and respiratory rate(RR)were significantly higher(P<0.05);Lower pain threshold(P<0.0001);The open field experiment shows that the moving distance and residence time of the edge are longer(P<0.001).Serum non-targeted metabolomics result showed that,compared with WKY group,the SHR group had 114 metabolites with significant differences(P<0.05).These differential metabolites were mainly lipids and lipid-like molecules(40.35%),organic acids and derivatives(22.8%),and organoheterocyclic compounds(15.79%).A total of 25 metabolic pathways were identified by KEGG enrichment analysis.Further differential abundance analysis showed that 16 pathways were activated,only 4 pathways were inhibited,and 5 pathways were not significantly changed.The glutamatergic synapse and GABAergic synapse were activated,while the serotonergic synapse was inhibited.Conclusions The symptoms of SHR include impatience and irritability,peripheral vascular dilation and collateral circulation formation,bulbar conjunctival congestive swelling,red tongue coloration,a dry tongue,constipation,red-yellow urine of low volume,and a rapid heart rate and high respiratory rate.All these suggest that SHR is a syndrome of hypertension with hyperactivity of liver-yang.The material basis of SHR is not only related to lipid,amino acid,and carbohydrate metabolism disorders,but also may be related to metabolic disorders of glutaminergic,GABAergic,and serotonergic neural pathways.
2.Study on the characteristics of Chinese medicine syndromes and its basic metabolites of spontaneously hypertensive rats
Qiuju ZHANG ; Yu WANG ; Bishi LING ; Meilong SI ; Haoxian MENG ; Mengyuan TIAN ; Ming ZHANG ; Nini LIAN ; Wanrong KANG ; Hua JIN
Acta Laboratorium Animalis Scientia Sinica 2025;33(1):44-53
Objective To investigate the characteristics of Chinese medicine syndromes and the possible metabolic substance basis of spontaneously hypertensive rat(SHR).Methods 10-week-old SPF SHR and WKY of the same strain were divided into SHR group and WKY group with 8 rats in each group.The general state,temperament,peripheral vascular filling,tongue characteristics,diet,water intake,urine and feces volume and characteristics,blood pressure,heart rate,respiratory rate,pain threshold,and open field behavior of SHR rats were observed and tested comprehensively to identify the possible syndrome types of Chinese medicine.At the same time,liquid chromatography tandem mass spectrometry was used to analyze non-targeted serum metabolites to preliminarily reveal the material basis of blood pressure elevation and Chinese medicine syndrome manifestations.Results Compared with WKY group,the scores of dark yellow hair color,irritable degree and peripheral capillary filling were higher in SHR group(P<0.0001).Red tongue color,dry tongue,little body fluid;24 h diet and water intake,urine volume and fecal volume were less(P<0.05),fecal water content was lower(P<0.001);systolic blood pressure(SBP),diastolic blood pressure(DBP),mean arterial pressure(MAP),heart rate(HR)and respiratory rate(RR)were significantly higher(P<0.05);Lower pain threshold(P<0.0001);The open field experiment shows that the moving distance and residence time of the edge are longer(P<0.001).Serum non-targeted metabolomics result showed that,compared with WKY group,the SHR group had 114 metabolites with significant differences(P<0.05).These differential metabolites were mainly lipids and lipid-like molecules(40.35%),organic acids and derivatives(22.8%),and organoheterocyclic compounds(15.79%).A total of 25 metabolic pathways were identified by KEGG enrichment analysis.Further differential abundance analysis showed that 16 pathways were activated,only 4 pathways were inhibited,and 5 pathways were not significantly changed.The glutamatergic synapse and GABAergic synapse were activated,while the serotonergic synapse was inhibited.Conclusions The symptoms of SHR include impatience and irritability,peripheral vascular dilation and collateral circulation formation,bulbar conjunctival congestive swelling,red tongue coloration,a dry tongue,constipation,red-yellow urine of low volume,and a rapid heart rate and high respiratory rate.All these suggest that SHR is a syndrome of hypertension with hyperactivity of liver-yang.The material basis of SHR is not only related to lipid,amino acid,and carbohydrate metabolism disorders,but also may be related to metabolic disorders of glutaminergic,GABAergic,and serotonergic neural pathways.
3.Exploration on the Biological Implications of"Earth Deficiency and Wood Depression"Pathogenesis of Hypertension from Intestinal Flora-bile Acid Axis
Meilong SI ; Hua JIN ; Minke LIU ; Yu WANG ; Qiuju ZHANG ; Shuangfang LIU ; Bishi LING ; Shangwen QI
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(3):13-18
There is a bidirectional relationship between intestinal flora and bile acids,and the imbalance of intestinal flora-bile acid axis metabolism is closely related to hypertension.Based on classical TCM literature and clinical practice,this article found that"earth deficiency"is the important pathological basis of hypertension,"wood depression"is the initiating factor of hypertension,and"earth deficiency and wood depression"is the key pathogenesis of hypertension.Combined with the research results of modern medicine and molecular biology,it is considered that the imbalance of intestinal flora and abnormal bile acid metabolism are closely related to the"earth deficiency"and"wood depression"of TCM respectively,and the imbalance of intestinal flora-bile acid axis coincides with the"earth deficiency and wood depression"of TCM in the process of hypertension.It is of great theoretical and practical significance to explore the biological connotation of hypertension"earth deficiency and wood depression"from the perspective of intestinal flora-bile acid axis for guiding TCM to prevent and treat hypertension.
4.Effect of Zhengan Xifengtang on Blood Pressure and Fecal Microflora of Spontaneously Hypertensive Rats
Shuangfang LIU ; Hua JIN ; Bishi LING ; Shangwen QI ; Meilong SI ; Qiuju ZHANG ; Yu WANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(13):76-85
ObjectiveTo observe the effect of Zhengan Xifengtang on blood pressure and fecal microflora of spontaneously hypertensive rats (SHRs). MethodA total of 75 male SHRs aged nine weeks were randomly divided into SHR group, Benazepril group (1.00 mg·kg-1·d-1), high-dose Zhengan Xifengtang group (34.5 g·kg-1·d-1), medium-dose Zhengan Xifengtang group (17.25 g·kg-1·d-1), and low-dose Zhengan Xifengtang group (8.625 g·kg-1·d-1). A total of 15 male Wistar-Kyoto (WKY) rats aged nine weeks were selected as the normal group. The normal group and SHR group were administrated with an equal volume of distilled water for eight weeks. During the administration, the blood pressure of the rats was measured regularly. After the intervention, fresh feces were collected with a sterile frozen storage tube, and 16S amplicon information was collected and analyzed. Plasma, hippocampus, and ileum of rats were collected for ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) detection. ResultZhengan Xifengtang decreased the systolic blood pressure and diastolic blood pressure of SHRs. Compared with the SHR group, Zhengan Xifengtang decreased the diversity of fecal microflora of SHRs. At the phylum level, Zhengan Xifengtang increased the relative abundance of SHR Verrucomicrobia and Actinobacteria and decreased the relative abundance of Synergistetes, Tenericutes, and Candidatus Saccharibacteria. Compared with the SHR group, Zhengan Xifengtang increased the relative abundance of Blautia wexlerae, Fusicatenibacter saccharivorans, and Akkermansia muciniphila and decreased the relative abundance of Clostridium lavalense, Intestinimonas butyriciproducens, Acetatifactor muris, Alloprevotella rava, and Oscillibacter valericigenes. Spearman correlation analysis showed that the systolic blood pressure of rats was negatively correlated with the relative abundance of Ethanoligenens, Aerococcus, Butyrivibrio, Olsenella, Bifidobacterium, Clostridium XIVb, Allobaculum, and Fusicatenibacter and positively correlated with the relative abundance of Alloprevotella. Zhengan Xifengtang increased the contents of plasma, hippocampal 5-hydroxy tryptamine(5-HT), and 5-hydroxyindole acetic acid(5-HIAA) in SHRs and decreased the contents of 5-HT and 5-HIAA in the ileum, and the content of 5-HT in the hippocampus was negatively correlated with that in the ileum. ConclusionZhengan Xifengtang can reduce the blood pressure of SHRs, which may be related to reducing the diversity of SHR microflora, regulating the structure of the microflora, increasing the relative abundance of 5-HT and short-chain fatty acids bacteria, and lowering the relative abundance of pathogenic bacteria related to intestinal inflammation.
5.Molecular mechanisms of appetite regulation system-mediated hypertension
Shangwen QI ; Bishi LING ; Hua JIN ; Shuangfang LIU
Chinese Journal of Pathophysiology 2024;40(8):1536-1541
The appetite regulation system is important for improving metabolism,regulating energy,and maintaining body weight by promoting/inhibiting appetite neurons/factors.Recent studies have shown that the appetite reg-ulation system can directly affect various hypertension-related pathophysiological processes,including sympathetic excita-tion,water and sodium retention,vascular damage,and oxidative stress.This review summarizes the roles of central appe-tite neurons,central appetite factors,and peripheral appetite factors in the pathogenesis of hypertension.

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