| Purpose: To summarize the tutor's understanding and treatment of dyslipidemia in traditional Chinese medicine and systematically evaluate the effect and safety of the method of invigorating the Spleen to eliminate phlegm for treatment for dyslipidemia.Meanwhile,the effect and mechanism of this method on abnormal lipoprotein metabolism and the relating vascular endothelial damage causing AS in hyperlipidemia spleen deficiency and phlegm syndrome animal model of Bama minipigs were investigated.Material and method:1.To summarize the traditional Chinese medicine theories and treatment methods on dyslipidemia by learning from the teacher clinically.2.China National Knowledge Infrastructure Database(CNKI),Wanfang Database,Chongqing VIP Database(VIP),China Biology Medicine Database(CBM),MEDLINE(Pubmed),and Cochrane Library were retrieved with the deadline on Novermber 19,2020.The inclusion trials of dyslipidemia were the method of invigorating the Spleen to eliminate phlegm together with basic treatment to basic treatment.The risk of bias of Cochrane handbook and Rev Man 5.4 were conducted by authors.3.A total of 15 female Bama mini-pigs(3-4 months,15?25kg)were fed with regular feed during the 1-week adaptive period,followed by random number table method into three groups: mini-pigs provided with basal feed(control group,n = 5),mini-pigs fed with high-fat diet(model group,n = 5),and mini-pigs provided with high-fat diet and the Chinese medicine herb intervention which invigorates the spleen to eliminate phlegm(treatment group,n = 5),and single cage(120cm long,80 cm wide and 83 cm high)was kept.The course was 24 weeks.After soothing the pigs,fasting blood was obtained from the ear vein and collected into tubes containing heparin and centrifuged at 1500 g for 15 min to obtain plasma for lipid profile results(total cholesterol,triglyceride,low density lipoprotein cholesterol,high density lipoprotein cholesterol,apolipoprotein AI,week 0,12,24),dysfunctional high density lipoprotein cholesterol parameters(myeloperoxidase,Paraoxonase1,high density lipoprotein cholesterol-apolipoprotein AI,high density lipoprotein cholesterol-Serum amyloid A,high density lipoprotein cholesterol-Paraoxonase1,week 0,12,24)and parameters of endothelial function(endothelial nitric oxide synthase,total nitric oxide synthase,inducible nitric oxide synthase,nitric oxide,endothelin-1 and intercellular adhesion molecule 1,week 24).At the end of week 24,after 8–12 h fasting,pigs were slaughtered at the experimental abattoir.After electrical stunning and exsanguination,samples for parameters of endothelial function,m RNA and protein expressions analysis were collected from the left anterior descending coronary artery endothelium and kept at-80°C,until analysis.Lipid profile results were assessed by automatic biochemical analyzer(TBA-120FR).Other parameters of dysfunctional HDL were measured by enzyme-linked immunosorbent assay.Premeters of endothelial function(nitric oxide,endothelial nitric oxide synthase,inducible nitric oxide synthase,total nitric oxide synthase,endothelin-1 and intercellular adhesion molecule 1)were measured by enzyme-linked immunosorbent assay.The level of indicators of dysfunctional HDL(myeloperoxidase,Paraoxonase1,high density lipoprotein cholesterol-apolipoprotein AI,high density lipoprotein cholesterol-Serum amyloid A,high density lipoprotein cholesterol-Paraoxonase1)were measured by enzyme-linked immunosorbent assay while the content of sphingosine-1-phosphate in blood was determined by high performance liquid chromatography(LC-20AT).The protein and m RNA expressions of the sphingosine-1-phosphate receptor 1/phosphatidylinositol 3-kinase /protein kinase B signal pathway in endothelium were measured by western blot and reverse transcription-polymerase chain reaction respectively.Results:1.Professor Yang said that,dysfunction of the spleen to transport;such as an insufficient ability to transport excess lipids,leads to an endogenous phlegmturbidity of which progressively leads to an obstruction in blood flow,which is the equivalent of dyslipidemia in western medicine.In the process of treatment,while keeping the pathogenesis of " an insufficient ability to transport excess lipids,leads to an endogenous phlegmturbidity",effectively applying the idea of "spleen governing transformation and transportation",the Chinese medicine herb which invigorates the spleen to eliminate phlegm interfering with dyslipidemia guided by traditional Chinese medicine theory,and with rich clinical experience for years,achieve good curative effect.2.1574 patients from eighteen studies were included.Meta-analysis results showed that,the Chinese medicine herb intervention which invigorates the spleen to eliminate phlegm combined with conventional treatment of dyslipidemia has better effect in improving the total clinical effective rate,reducing the plasma total cholesterol,triglyceride and low density lipoprotein cholesterol levels,increasing the plasma high density lipoprotein cholesterol and Apolipoprotein AI levels,improving the symptoms of traditional Chinese medicine and reducing the syndrome score of traditional Chinese medicine,and the incidence of adverse reactions is lower,which were all with a statistically significant difference.Compared with conventional treatment of western medicine,the method of invigorating the spleen to eliminate phlegm for treatment for dyslipidemia alone showed similar efficacy in reducing total cholesterol,triglyceride,low density lipoprotein cholesterol and increasing high density lipoprotein cholesterol,apolipoprotein AI,and there was no statistical difference(P>0.05).All the adverse events reported in the included studies were mild,including constipation,abdominal distension,diarrhea,abdominal pain,nausea,rash,headache,and elevated transaminase,etc.Most recovered after drug withdrawal,and no serious adverse events were reported in the trial.The incidence of adverse events decreased with the combination of conventional Western medicine treatment with the method of invigorating the spleen to eliminate phlegm,and the difference was statistically significant(P<0.05)?3.The method of invigorating the spleen to eliminate phlegm significantly reduced serum triglyceride and low density lipoprotein cholesterol contents(P<0.01 or P<0.05),and reduced serum total cholesterol content of the model(P>0.05),while significantly elevated serum Apolipoprotein AI content(P<0.01).Meanwhile,there was no significant difference in high density lipoprotein cholesterol level between the treatment and model group,but the method of invigorating the spleen to eliminate phlegm increased high density lipoprotein cholesterol content to some extent(P>0.05).In terms of efficacy in correcting dysfunctional high density lipoprotein cholesterol,the method significantly reduced serum myeloperoxidase and high density lipoprotein cholesterol-Serum amyloid A contents(P<0.01),while significantly elevated serum high density lipoprotein cholesterol-apolipoprotein AI,high density lipoprotein cholesterol-sphingosine-1-phosphate,high density lipoprotein cholesterol-Paraoxonase1 contents(P<0.01).elevated serum paraoxonase1 content(P<0.05).The ratio of myeloperoxidase / Paraoxonase1 decreased significantly(P<0.01),The ratio of high density lipoprotein cholesterol-Serum amyloid A / high density lipoprotein cholesterol-apolipoprotein AI decreased(P<0.05).In terms of improving endothelial function,the serum levels of total nitric oxide synthase,inducible nitric oxide synthase endothelin-1 and intercellular adhesion molecule 1 were significantly increased,and the levels of endothelial nitric oxide synthase and nitric oxide were significantly decreased in hyperlipidemia spleen deficiency and phlegm syndrome animal model of Bama minipig.The Chinese medicine herb intervention,which invigorates the Spleen to eliminate phlegm,significantly decreased the serum levels of total nitric oxide synthase,inducible nitric oxide synthase,endothelin-1 and intercellular adhesion molecule 1(P < 0.01),and significantly increased the level of endothelial nitric oxide synthase(P < 0.01)and the level of nitric oxide(P < 0.05)in pigs with hyperlipidemia.The changes of endothelial function indexes in endothelial homogenate of each group were consistent.The results showed that the m RNA expressions of sphingosine-1-phosphate receptor 1,phosphatidylinositol 3-kinase and protein kinase B in vascular endothelium of pigs with hyperlipidemia were significantly decreased(P < 0.01),and the expression of endothelial nitric oxide synthase was also decreased(P < 0.05).The Chinese medicine herb significantly increased the m RNA expression of sphingosine-1-phosphate receptor 1,phosphatidylinositol 3-kinase and protein kinase B in vascular endothelium(P <0.01),and increased the m RNA expression of endothelial nitric oxide synthase(P < 0.05).The protein expressions of sphingosine-1-phosphate receptor 1,phosphatidylinositol 3-kinase and protein kinase B were decreased(P < 0.05),the protein expression of endothelial nitric oxide synthase was significantly decreased(P < 0.01),and the protein expression of inducible nitric oxide synthase was significantly increased(P < 0.01).TCM for invigorating spleen and removing phlegm increased the protein expression of sphingosine-1-phosphate receptor 1,phosphatidylinositol 3-kinase and endothelial nitric oxide synthase(P < 0.05),significantly increased the protein expression of protein kinase B(P < 0.01),and decreased the protein expression of inducible nitric oxide synthase(P < 0.05).Conclusion:1.The etiology and pathogenesis of abnormal blood lipid in Chinese medicine is " an insufficient ability to transport excess lipids,leads to an endogenous phlegmturbidity ".The instructor takes " spleen governing transformation and transportation" as the guiding principle and "restoring spleen governing transformation and transportation,removing phlegm and turbidity,regulating spleen to regulate blood lipid" as the treatment principle,and has a significant effect on the treatment of abnormal blood lipid.2.The Chinese medicine herb intervention,which invigorates the Spleen to eliminate phlegm,has good efficacy and safety in the treatment of dyslipidemia.3.The Chinese medicine of invigorating spleen and removing phlegm can improve the level of blood lipid,reduce the content of dysfunctional high density lipoprotein cholesterol,and improve the vascular endothelial function of pigs with spleen deficiency and phlegm turbid hyperlipidemia,which is related to the activation of the sphingosine-1-phosphate receptor1/phosphatidylinositol 3-kinase /protein kinase B signaling pathway which is inhibited in the vascular endothelial of hyperlipidemia spleen deficiency and phlegm syndrome animal model of Bama minipig. |
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