| Objective:1.Clinical observation on the efficacy and safety of Shenhong Tongluo Granules in treating unstable angina pectoris patients with qi deficiency and blood stasis,and phlegm obstruction.2.Animal experiments were conducted to observe the effects the Chinese medicine of Shenhong Tongluo Granule on plaque,blood lipid levels,non-targeted metabolites,bile acid metabolism,and other related indicators in AS mice,and to explore the potential anti-AS mechanism of the Chinese medicine of Shenhong Tongluo Granule.Methods:1.Seventy-two patients from the Cardiology Department of Affiliated Hospital of Changchun University of Traditional Chinese Medicine from February 1,2022 to December1,2022 were randomly divided into a control group（N=36 cases）and an experimental group（N=36 cases）.The control group received routine Western medicine treatment,while the experimental group received a combination of Shenhong Tongluo granules on the basis of the control group.The treatment period was all 4 weeks.Observe the general situation of two groups of patients before treatment,the changes in angina efficacy scores before treatment,2 weeks of medication,and 4 weeks of medication,as well as changes in blood lipid levels,incidence of cardiovascular events,traditional Chinese medicine syndrome efficacy and symptom scores,electrocardiogram efficacy,Seattle Angina Scale scores,and safety indicators before and after treatment,in order to evaluate the efficacy and safety of Shenhong Tongluo Granules in treating unstable angina pectoris.2.Sixty male ApoE-/-mice were randomly divided into model group,SHTL group,and positive drug group,with 20 mice in each group.They were given D12109C high fat diet;Twenty C57BL9/J male mice were used as a blank group,and were given normal diet for maintenance.After 8 weeks,the SHTL group was given Shenhong Tongluo Granule solution,the positive drug group was given rosuvastatin calcium solution,and both the blank group and the model group were given equal volume of high-temperature high-pressure sterilized water.At the 8th week of administration,mouse feces were collected.After 8 weeks of administration,tissues such as serum,heart,aorta,and liver were taken.The aorta and aortic sinuses of mice were stained with oil red O,and the contents of TC,TG,HDL-C,and LDL-C in mouse serum were measured.3.Using non targeted metabolomics techniques,significant differences in metabolites and related KEGG pathways in the feces of mice after intervention with Shenhong Tongluo Granules were screened..4.RT-PCR and WB were used to detect the gene expression and protein level of CYP7A1,CYP7B1,CYP8B1,CYP27A1,and FXR in mouse liver.Results:1.A total of 72 patients were enrolled in this study.During the treatment process,there were 4 cases of dropout in the control group,3 cases of dropout in the experimental group,and 32 cases in the final effective case control group and 33 cases in the experimental group,totaling 65 cases.There was no statistically significant difference（P>0.05）between the two groups of patients in terms of gender,age,course of disease,angina grading,risk stratification,and comorbidities when enrolled,indicating good baseline comparability.Compared with before treatment,the score of angina pectoris in the two groups of patients significantly decreased after 2 and 4 weeks of treatment,and the difference was statistically significant（P<0.05）;The therapeutic effect of angina pectoris in the experimental group was higher than that in the control group after treatment,and the difference was statistically significant（P<0.05）;After treatment,the blood lipid levels of TG,TC,and LDL-C in both groups of patients were significantly reduced compared to before treatment（P<0.05）,and the experimental group was significantly lower than the control group（P<0.05）;The incidence of cardiovascular events in the experimental group after treatment was lower than that in the control group,but there was no significant difference（P>0.05）;The electrocardiogram efficacy of the experimental group after treatment was better than that of the control group,but there was no significant difference（P>0.05）;The treatment of both groups can reduce the TCM syndrome score,improve the TCM syndrome efficacy,reduce the Nitroglycerin stop rate,and improve the five dimensions of SAQ score,and the effect of the test group is better,the difference is statistically significant（P<0.05）;Both groups of patients showed no significant abnormal changes in safety indicators during treatment,and no other adverse reactions occurred.2.Comparison of the percentage of plaque formation area between AS plaque and aortic sinus plaque:Compared with the blank group,the model group significantly increased,with a statistically significant difference（P<0.05）;Compared with the model group,the SHTL group and the positive drug group were significantly reduced,with a statistically significant difference（P<0.05）;Compared with the SHTL group,the positive drug group was less,with a statistically significant difference（P<0.05）.Blood lipid test results:Compared with the blank group,the levels of TC,TG,LDL-C in the model group were significantly increased,while HDL-C was significantly decreased（P<0.05）.Compared with the model group,the levels of TC,TG,and LDL-C in SHTL and positive drug groups were significantly decreased,while HDL-C was significantly increased（P<0.05）.3.The results of non-targeted metabolomics testing showed that compared with the model group,the metabolites in the blank group and the SHTL group had significant differences,mainly belonging to lipids and lipid molecules（41.379%）,organic acids and their derivatives（20.690%）,and organic heterocyclic compounds（13.793%）.Analysis of the KEGG pathway revealed that these metabolites are most closely related to primary bile acid biosynthesis,cholesterol metabolism,and bile secretion,especially primary bile acid biosynthesis.4.The results of RT-PCR and WB showed that compared with the blank group,the gene expression and protein levels of CYP7A1,CYP7B1,CYP8B1,CYP27A1,FXR in the liver of the model group were significantly increased;Compared with the model group,the gene expression levels and protein levels of CYP7A1,CYP7B1,CYP8B1,and CYP27A1 in the SHTL group were significantly increased,while the gene expression and protein levels of FXR were significantly decreased.Conclusion:1.Clinical trials have shown that SHTL can effectively improve unstable angina pectoris,reduce blood lipid levels,improve traditional Chinese medicine syndrome efficacy,improve patient quality of life,and have high medication safety.2.Animal experiments have shown that SHTL can inhibit the formation of aortic plaques in AS mice,reduce blood lipid levels,and intervene in the progression of AS.3.Based on non targeted metabolomics methods,it was found that the main targets of SHTL’s anti-AS effects are lipids and lipid molecules,organic acids and their derivatives,and organic heterocyclic compounds.The enrichment pathway results showed a close relationship with primary bile acid biosynthesis,cholesterol metabolism,and bile secretion,especially the primary bile acid biosynthesis pathway,indicating that the potential mechanism of Shenhong Tongluo’s anti-AS effect may be related to regulating primary bile acid synthesis.4.SHTL may regulate key factors of primary bile acid synthesis pathway,promoting the synthesis of primary bile acids,thereby promoting the metabolism of cholesterol and lipids,reducing the body’s blood lipid levels,and exerting anti-AS effects. |
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