The Mechanism Study Of The Protective Effect Of Eucommia Ulmoides&Tribulus Terrestris Herb Couples On Neurological Injury Caused By Angiotensin ? By Regulating LncRNAs

OBJECTIVE: To analyze the core drug pairs of the instructors in the treatment of senile hypertension with mild cognitive impairment,to find out the expression profile of lnc RNA in the intervention of elderly patients with hypertensive neurological injury,and to screen out the potential regulatory lnc RNA for further study.Research and discover new pharmacological mechanisms to provide evidence.Methods: 1.Collect data of patients with mild cognitive impairment of senile hypertension in the instructor's outpatient department,and analyze the prescriptions and combine the results of modern pharmacological research to screen out the core drug pairs for treating this disease.2.Using the Integrated Pharmacology Platform(TCMIP)to identify known active components of core drug pairs and predict their intervention in hypertension and cognitive impairment as a pre-experimental evaluation.3.Liquid-based tandem mass spectrometry(LC-MS/MS)was used to detect the neuroprotective effects of drug nerve cells,and the active constituents of angiotensin ?(Ang ?)were explored.The main principles of drug absorption are used to identify absorbable components,and the target of these components is analyzed by bioinformatics to predict its mechanism of action.4.The MTT method screens the ratio of the effective part and the best effective part of the drug pair.Furthermore,the effects of SH-SY5 Y proliferation,apoptosis and energy metabolism were observed by flow cytometry and seahorse cell energy metabolism experiments.The lnc RNA combined with m RNA gene sequencing was used to detect the effective site of Chinese medicine to interfere with the expression profile of lnc RNA induced by Ang ? in SH-SY5 Y.The regulation mechanism of lnc RNA was studied by bioinformatics analysis methods such as GO and KEGG.Screen the key lnc RNA for validation analysis.Results: 1.A total of 102 general information and prescriptions for elderly patients with hypertension and comorbid mild cognitive impairment were collected from the instructor's outpatient department.A total of 124 kinds of traditional Chinese medicines were selected,with 1369 flavors,with an average of 11.04 flavors per side.There are 11 kinds of drugs that use more than 40 times: Angelica,Astragalus,Alisma,Robinia,Achyranthes,Eucommia,Suanzaoren,Astragalus,Mulberry,Coptidis Rhizome,and Danpi,which are screened to obtain the core drug against Eucommia ulmoides.2.TCMIP results showed that Eucommia-Hedgehog had 26 effective interventions for hypertension and cognitive impairment,involving 39 key targets and 30 core pathways.Mainly involved in circulatory and neurological function regulation,associated with inflammation,oxidative stress,and mitochondrial dysfunction with aging.3.LC-MS/MS results showed that the active constituents of Robinia pseudoacacia were associated with regulation of inflammation,oxidative stress and mitochondrial dysfunction of aging.The MTT method was used to screen the ratio of effective parts and concentration of Eucommia ulmoides Oliv.and Robinia pseudoacacia.The ratio of geniposide(0.1mg/L)to E.fuliginea Fr.10(5mg/L)was 1:1.5.Gene sequencing revealed differential lnc RNA and differential m RNA,and analysis showed that lnc RNA improved neuronal damage by affecting the sphingolipid metabolic pathway.Conclusion: 1.The status of cognitive disorder of hypertension comorbidity in the elderly is in the liver and kidney.The pathological nature is the virtual standard.The liver and kidney deficiency are the main factors,and the heat and heat are the standard.Liver and kidney deficiency,blood circulation is unfavorable,brain dystrophy is the core pathogenesis of senile hypertension cognitive disorder.The treatment is based on nourishing liver and kidney,and it is also used to clear away heat and purify fire,promote blood circulation and remove phlegm.Based on the experience of the instructor,the use of drug-based taste is mostly warm and cold,with sweet,bitter and symplectic as the mainstay,returning to the liver and kidney.Combined with the research results of modern pharmacology,the drug pairs with antihypertensive and neuroprotective effects were selected,namely the Eucommia ulmoides-Hedgehog pair.3.The antihypertensive and neuroprotective mechanisms of Eucommia ulmoides-Hedgehog are related to the regulation of Lnc RNA.Bioinformatics analysis showed that lnc RNA is likely to play a regulatory role by regulating the signaling pathway of sphingolipid metabolism.Lnc RNA ENST00000437438 affects sphingolipid metabolism by regulating the expression of NEU4.