Metabolic Disorder Of Normal High Blood Pressure And Intervention Study Of Sanzi Yangqin Decoction

Objective: To evaluate the effect of Sanzi Yangqin Decoction in regulating metabolic disorders in high-normal blood pressure rats;to explore the metabolic disorders in the highnormal blood pressure stage and its relationship with TLR4 signaling pathwayMethods: 1.High-fat + high-salt method was used to prepare a rat model of normal high blood pressure,and the changes in blood pressure,body weight and body length of the rats before and after the intervention of Sanzi Yangqin Decoction were observed;enzymelinked immunosorbent assay(ELISA)method was used to detect the drugs in rats After intervention,serum lipid levels,high-sensitivity C-reactive protein,NO,and TNF-α levels were detected by ultra-high performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry(UPLC-Q-Orbitrap MS)method.The endogenous metabolites in rat serum were identified,and the biomarkers and metabolic pathways of Sanzi Yangqin Decoction intervention in normal and high blood pressure rats were identified,and the relative content changes of the main biomarkers were further analyzed by pseudo-targeted metabolomics.2.Spontaneously hypertensive rat(SHR)and Wistar-Kyoto rat(WKY)rat models were used to analyze the biomarkers and metabolic pathways associated with high normal blood pressure through non-targeted metabolomics and correlation analysis;ELISA was used The content of NO,ET-1,IL-6,TNF-α and NF-κB in serum of rats of different weeks of age was detected by the method;HE & Masson staining was used to observe the changes of aortic vascular endothelium of rats of different weeks of age;RT-PCR The expressions of related proteins and genes in the TLR4 signaling pathway in rats of different ages were detected by Western blot method;the expressions of TLR4 and MyD88 in the aortas of rats of different ages were analyzed by immunofluorescence.Results: 1.(1)The high-dose Sanzi Yangqin Decoction group can effectively reduce blood pressure,Lee’s index,and serum TC,TG,LDL,and TNF-α levels in normotensive rats,and increase NO levels.(2)Non-targeted metabolomics data analysis found that there were significant metabolic differences after Sanzi Yangqin Decoction intervention,and 31 differential metabolites were screened out,involving linoleic acid metabolism,sphingolipid metabolism,and arachidonic acid metabolism.Further through the pseudo-targeted metabolomics analysis,the contents of arachidonic acid,thromboxane B2,prostaglandin D2,lysophosphatidylcholine,lysophosphatidic acid and lysophosphatidylethanolamine in the serum of rats after Sanzi Yangqin decoction intervention The decrease of sphingosine content indicates that Sanzi Yangqin Decoction regulates the content of metabolites through linoleic acid metabolism,arachidonic acid metabolism and sphingolipid metabolism,thereby reducing blood pressure,blood lipids and inflammatory factor levels,and regulating metabolic disorders.2.Un-targeted metabolomic analysis screened out biomarkers related to normal high blood pressure stage,involving glycerophospholipid metabolism,sphingolipid metabolism and arachidonic acid metabolism.The results of ELISA showed that the levels of IL-6,TNF-α and NF-κB in serum increased with age.PCR and WB results showed that the mRNA and protein levels of TLR4,My D88,cPLA2,and NF-κB were up-regulated in SHR with age.NO and eNOS were decreased in serum and aorta respectively,and ET-1 was increased in serum.The above results indicate that activation of TLR4 signaling pathway related to arachidonic acid metabolism causes metabolic disorder and aggravation of inflammation,and promotes the continuous increase of blood pressure.Conclusion: 1.Sanzi Yangqin Decoction can improve the metabolic state of normal high blood pressure rats by regulating the levels of differential biomarkers by regulating linoleic acid metabolism,arachidonic acid metabolism and sphingolipid metabolism pathways.2.The increase of blood pressure in normal high blood pressure involves glycerophospholipid metabolism,sphingolipid metabolism and arachidonic acid metabolism.Abnormal arachidonic acid metabolism is closely related to the increase of blood pressure,and the activation of TLR4 signaling pathway is involved in the increase of blood pressure.Metabolic disturbances and vascular inflammation in high processes.