| According to China's epidemiological statistics,coronary heart disease has a increasing trend year by year.Its incidence is mainly caused by high-calorie,high-cholesterol food intake,social pressure,emotional irritability,and decreased physical activity.That is to say,the Chinese medicine said that the diet is not harmonious,emotional disorders,and work and rest;for this reason,Chinese medicine believes that the mechanism of coronary heart disease is also changed from the ancient Yang yin chord,yang deficiency cold condensate to phlegm heat and blood stasis many.With the global warming,changes in dietary structure,and changes in mental stress,the proportion of syndromes in coronary heart disease syndrome is increasing.Patients with coronary heart disease and heat syndrome often show clinical symptoms such as irritable and anxiety.From the perspective of modern medicine,they are consistent with the state of sympathetic excitation.According to many years of clinical and basic research,with the accelerated pace of life,increased work pressure,changes in diet,etc.,patients with coronary heart disease and heat syndrome are more likely to have palpitations,chest pain,chest tightness,insomnia,upset,Temperament,anxiety,dry mouth and drink,dry stool,short red urine,red tongue yellow(or yellow greasy),pulse string slippery,etc.are sympathetic excitatory manifestations,given the Chinese medicine for clearing away heat and phlegm,often available Good curative effect;based on this,a large number of clinical and basic experimental studies have been carried out.Even Xia Ningxin granules are obtained from Huanglian Wendan Decoction,which is suitable for clearing heat and removing phlegm,especially for various heart diseases such as syndromes of Chinese medicine,heat,disease,or sympathetic excitation factors of Western medicine.It is arrhythmia and has a remarkable effect.This study systematically expounds the clinical effects of Qingre Huayu method represented by Lianxia Ningxin granule on coronary heart disease patients with angina pectoris from the three aspects of literature research,clinical research and basic research,and from its active component berberine,Hesperidin inhibits the conversion of cardiac fibroblasts into myofibroblasts by inhibiting the Notch1 pathway,thereby inhibiting NGF expression and inhibiting cardiac sympathetic remodeling to reduce arrhythmia and palpitations.Part of the relevant mechanisms of clinical impact in patients with angina pectoris.Study 1 Literature ResearchThe research progress of the syndrome of heat-stasis in coronary heart disease was reviewed,and some related mechanisms of the treatment of coronary heart disease with Qingre Huayu method were systematically combed.Study 2 Clinical inquiryObjective:To investigate the effect of Qingre Huayu method represented by Lianxia Ningxin granule on clinical efficacy,symptoms and quality of life in patients with angina pectorisMethods:Sixty patients with coronary heart disease and angina pectoris were randomly assigned to a treatment group and a control group.The treatment group was given Lianxia Ningxin Granules and Western medicine.The control group was given placebo and Western medicine.After the treatment,the angina pectoris grading,the sputum heat syndrome scale and the palpebral symptom score,and the Seattle scale were compared to further verify the treatment of Qingxin Huatan method in improving the symptoms and quality of life of patients with angina pectoris,effect.Results:After 4 weeks of treatment,the angina pectoris in the treatment group was better than the control group.The score of the sputum heat syndrome was lower than that of the control group.The score of palpitations was lower than that of the control group,and the score of the Seattle scale was higher than that of the control group.Conclusion:The method of clearing away heat and removing phlegm represented by Lianxia Ningxin granules can improve the curative effect on angina pectoris of coronary heart disease,improve the curative effect of TCM syndrome,improve the symptoms of palpitations and improve the quality of life.Study 3 Experimental ResearchObjective:To study the effect of clearing phlegm and blood stasis on the expression of NGF in fibroblasts mediated by TGF-?1-stimulated Notchl pathway,an effective component of Xia Ningxin granules and berberine.Methods:The primary CFS was isolated by differential adherence method.The third CFS was divided into blank group,model group,berberine group and hesperidin group.The blank group was cultured in serum-free medium,and the model group was treated with TGF-?1.The berberine group was further added with high,medium,low and micro concentrations of berberine on the model group.The hesperidin group was On the basis of the model group,four concentrations of hesperidin in high,medium,low and micro concentrations were added to detect cell proliferation,a-SMA,Hes1,Hey1,and NICD by qPCR,Western Blot,immunocytochemistry,and CCK8.,NGF and Hes1,Heyl,NGF mRNA expression levels,and the mechanism and mechanism of Notchl pathway-mediated berberine and hesperidin in the secretion of NGF by cardiac fibroblasts stimulated by TGF-?1Results:(1)Cell proliferation assay:Compared with the blank group,the absorbance of CCK8 was significantly increased in the model group after TGF-?1 stimulation(P<0.01).(2)The effect of cell expression on a-SMA protein:In comparison,the expression level of a-SMA protein in the model group was significantly increased(P<0.01).The expression levels of a-SMA protein in the berberine group and the hesperidin low-middle group were significantly lower(P<0.05)when comparing with the model group,the expression level of a-SMA was inversely proportional to the dose of berberine and hesperidin.(3)Effect on Hes1 expression in cells:The expression level of Hes1 protein in the model group was significantly increased(P<0.01)when comparing with the blank group.The expression level of Hesl protein in each group of berberine and hesperidin was significantly decreased(P<0.05)when comparing with the model group,and the expression level of Hesl was inversely proportional to the dose of berberine and hesperidin.(4)The effect of Hey1 on cell expression:the expression level of Hey1 protein in the model group was significantly increased(P<0.01)when comparing with the blank group.,The expression level of Hey1 protein in each group of berberine and hesperidin group was significantly decreased(P<0.01)when comparing with the model group,and the expression level of Hey1 was inversely proportional to the dose of berberine and hesperidin.(5)Effects on the expression of NICD in cells:The expression level of NICD protein in the model group was significantly increased(P<0.41)when comparing with the blank group.The expression level of NICD protein in each group of berberine and hesperidin group was significantly decreased(P<0.01)when comparing with the model group,and the expression level of NICD was inversely proportional to the dose of berberine and hesperidin.(6)Effects on the expression of NGF in cells:The expression of NGF protein in the model group was significantly increased(P<0.01)when comparing with the blank group.The expression levels of NGF protein in the low,middle and high groups of hesperidin and all groups of berberine were significantly lower(P<0.05)when comparing with the model group,and the expression level of NGF was inversely proportional to the dose of berberine and hesperidin.(7)Effect on Hes1 mRNA expression in cells:The expression level of Hes1 mRNA in the model group was significantly increased(P<0.05)when comparing with the blank group.The expression level of Hesl mRNA in each group of berberine and hesperidin group was significantly decreased(P<0.05)when comparing with the model group,and the expression level of Hes1 mRNA was inversely proportional to the dose of berberine and hesperidin.(8)Effect on Hey1 mRNA expression in cells:The expression level of Hey1 mRNA in the model group was significantly increased(P<0.01)when comparing with the blank group.Compared with the model group,The expression level of Hey1 mRNA in the berberine group and the hesperidin group was significantly decreased(P<0.01)when comparing with the model group,and the expression level of Heyl mRNA was inversely proportional to the dose of berberine and hesperidin.(9)Effect on the expression of NGF mRNA in cells:The expression of NGF mRNA in the model group was significantly increased(P<0.01)when comparing with the blank group.The expression level of NGF mRNA in the berberine group and the hesperidin group was significantly decreased(P<0.01)when comparing with the model group,and the expression level of NGF mRNA was inversely proportional to the dose of berberine and hesperidin.(10)The effect of MMP1 expression on cells:The expression level of MMP1 in the model group was significantly higher when comparing with the blank group.The expression levels of MMP1 in each group of berberine and hesperidin were significantly lower when comparing with the model group.With the increase of berberine dose and hesperidin,the expression level of MMP1 gradually decreased.(11)The effect of MMP9 expression on cells:The expression level of MMP9 in the model group was significantly higher when comparing with the model group.The expression levels of MMP9 in each group of berberine and hesperidin were significantly lower when comparing with the model group.With the increase of berberine dose and hesperidin,the expression level of MMP9 gradually decreased.Conclusion:The phlegm and hesperidin,which are the effective components of the Chinese herbal medicine Lianxianingxin granules,can inhibit the transformation of cardiac fibroblasts into myofibroblasts by inhibiting the Notch1 pathway,thereby inhibiting the expression of NGF and inhibiting the heart.Reconstruction of sympathetic nerves reduces the occurrence of arrhythmia and palpitations. |
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