| Coronary heart disease is a common and frequently occurring disease,which seriously threatens people's health and life safety.With the accelerated pace of life,the increase of working pressure,the change of diet,etc.,phlegm-heat obstruction plays an important role in the occurrence and development of chest arthralgia,and clinical attention should be paid to the existence of phlegm-heat coronary heart disease patients.Clinical observation showed that the symptoms of patients with phlegm heat syndrome of coronary heart disease were consistent with the state of autonomic nervous dysfunction in modern medicine.Clinical observation showed that the symptoms of patients with phlegm heat syndrome of coronary heart disease were consistent with the state of autonomic nervous dysfunction in modern medicine.Studies have shown that the autonomic nervous system plays an important mediating role between"Heart is the master of blood" and "Heart is the master of god",Phlegm heat syndrome of coronary heart disease is closely related to autonomic nerve dysfunction.Professor Li Ping founded Lianxia Ningxin prescription.The whole prescription is composed of clearing away heat and resolving phlegm to smooth the blood vessels,calming the heart and calming the mind to regulate the spirit,so as to achieve the effect of blood and spirit treatment.The clinical study of this paper systematically elaborated the intervention effect of Lianxia ningxin prescription on heart rate variability(HRV)and plasma catecholamine(CA)in patients with phlegm-heat syndrome of coronary heart disease from the perspective of autonomic nervous system.In the early stage,the team established a high-performance liquid-electrospray-triple quadrupole mass spectrometry(HPLC-ESI-MS/MS)analysis,which showed that Coptidis Rhizoma and Rhizoma Pinelliae Preparata are the main components of Lianxia Ningxin prescription.Basic experiments used Lianxia formula granule to administer interventions to clarify the effects on HRV,plasma CA and inflammation in rats with myocardial infarction,and to explore the mechanism of Lianxia formula granule in improving sympathetic nerve remodeling from NGF/TrkA/PI3K/AKT signaling pathway.Study 1 Effect of Lianxia Ningxin prescription on HRV and plasma CA in patients with phlegm-heat syndrome of coronary heart diseaseObjective:To preliminarily evaluate the efficacy and safety of Lianxia Ningxin prescription in treating HRV and plasma CA in patients with phlegm-heat syndrome of coronary heart disease.Methods:A total of 80 patients with phlegm-heat syndrome of coronary heart disease(CHD)who met the admission criteria were enrolled in this study by a randomized controlled double-blind placebo trial.They were randomly assigned to the Lianxia Ningxin prescription treatment group and the placebo control group,40 cases in each group.The treatment group was given basic western medicine treatment combined with Lianxia Ningxin granules,while the control group was given placebo on the basis of conventional western medicine treatment for 4 weeks.HRV indexes(SDNN,SDNN index,SDANN,rMSSD,PNN50),plasma CA(Nrepinephrine(NE),Epinephrine(E)and Dopamine(DA))and phlegm-heat syndrome scale before and after treatment in 2 groups were statistically analyzed.To further verify the effectiveness of Lianxia Ningxin prescription on heart rate variability,plasma catecholamine and traditional Chinese medicine syndrome in patients with phlegm-heat syndrome of coronary heart diseaseResult:(1)In terms of heart rate variability,after 4 weeks of treatment,the SDNN,SDANN and pNN50 in the treatment group were increased,and the difference was significant(P<0.05),In the control group,the changes of each index were different,and the change trend was not significant(P>0.05).The difference between the two groups was statistically significant and better than that of the control group(P<0.05).There was no significant difference in other indexes between two groups(P>0.05).(2)In terms of plasma catecholamines,after 4 weeks of treatment,the NE index of the treatment group was significantly lower than before the treatment,and the difference was statistically significant(P<0.05),while the remaining index changes were not significant(P>0.05);There was no statistically significant difference within the control group(P>0.05).Comparing the groups after 4 weeks of treatment,the NE index of the treatment group was statistically significant compared with the control group,and was better than the control group(P<0.05).There was no statistically significant difference between the other index groups(P>0.05).(3)In terms of the phlegm-heat syndrome score,compared within the group,the difference after 2 weeks of treatment,after 4 weeks of treatment and before treatment was statistically significant in each group;The treatment group in the treatment of 4 weeks compared with 2 weeks of treatment,the difference was also statistically significant;However,there was no significant difference between 4 weeks and 2 weeks in the control group.In comparison between the groups,at 2 weeks of treatment,the scores of phlegm-heat syndrome in the two groups were equivalent,and the difference was not statistically significant(F=0.795,P=0.378);at 4 weeks of treatment,the scores of phlegm-heat syndrome in the treatment group were higher than those in the control group the scores of patients with phlegm-heat syndrome were significantly reduced,and the difference was statistically significant(F=9.789,P=0.003).(4)In terms of safety,there was no obvious abnormality of liver and kidney function and no obvious adverse reaction in the two groups.Conclusion:Lianxia Ningxin prescription can effectively improve HRV,reduce plasma CA and improve autonomic nervous function in patients with coronary heart disease with phlegm heat syndrome,but it needs to be further confirmed by a larger sample size.Study 2 Effect of Lianxia formula granule on HRV and plasma CA in rats with myocardial infarctionObjective:To observe the effect of Lianxia formula granule on HRV,plasma CA and inflammatory reaction in rats with myocardial infarction.Methods:the rat model of myocardial infarction was established by ligating the left anterior descending coronary artery.The successful SD rats were randomly divided into model group,Lianxia formula granule high,medium and low dose groups,metoprolol group and sham operation group.After 30 days of drug intervention,the ECG of lead ? was recorded.The low frequency power(LF),high frequency power(HF)and LF/HF ratio of HRV were measured.The contents of plasma CA and serum TNF-? and IL-I? were detected by ELISA.The expression of myocardial p38 protein was detected by Western blot,P38 mRNA level was detected by RT-PCR and pathological changes were observed by HE staining.Result:(1)HRV:Compared with the sham group,the LF and LF/HF of the model group were significantly reduced(P<0.01).Compared with the model group,Lianxia formula granule each dose group and Metoprolol group LF significantly increased(P<0.01),Lianxia formula granule high-dose group LF/HF significantly increased(P<0.01).The LF/HF of Lianxia formula granule middle dose group and Metoprolol group were significantly improved(P<0.05).There was no significant difference in HF between the groups(P>0.05).(2)Plasma C A:Compared with the sham group,the plasma CA level of rats in the model group was significantly increased(P<0.01).The plasma CA levels of rats in Lianxia formula granule groups and metoprolol group were significantly lower than those in the model group(P<0.01).(3)Serum TNF-? and IL-I?:Compared with the sham operation group,the serum TNF-?and IL-I? of the model group increased significantly(P<0.01).Compared with the model group,the serum TNF-? and IL-I? of rats in the Lianxia formula granule high-dose and medium-dose groups and metoprolol group were significantly reduced(P<0.01),and the serum TNF-? of the Lianxia formula granule low-dose group was significantly reduced(P<0.01),there was no significant change in IL-I? in the Lianxia formula granule low-dose group(P>0.05).(4)Myocardial P38 protein and mRNA:Compared with the sham operation group,the expression of P38 protein and mRNA in the myocardial tissue of the marginal zone of myocardial infarction in the model group increased significantly(P<0.01).Compared with the model group,the expression of P38 protein in the Lianxia formula granule high-dose group was significantly reduced(P<0.05),while the expression of P38 protein in the remaining groups had no significant difference(P>0.05).Compared with the model group,the expression of P38mRNA in Lianxia formula granule high-dose,medium-dose group and Metoprolol group was significantly reduced(P<0.01),and the P3 8mRNA expression of Lianxia formula granule low-dose group was significantly reduced(P<0.05).(6)HE staining:Compared with the sham group,the myocardial cells in the marginal area of myocardial infarction in the model group were swollen and arranged disorderly,and a large number of inflammatory cell infiltration appeared in the myocardial interstitium.The arrangement of myocardial fibers in each group of Lianxia formula granule and Metoprolol group was relatively neat,and the degree of inflammatory cell infiltration was significantly reduced.Conclusion:Lianxia formula granule can improve HRV in rats with myocardial infarction,reduce plasma catecholamine levels,and reduce inflammation.Study 3 The effect of Lianxia formula granule on sympathetic nerve remodeling in rats with myocardial infarction based on NGF/TrkA/PI3K/AKT signaling pathwayObjective:To explore the effect of Lianxia formula granule on sympathetic nerve remodeling in rats with myocardial infarction and its underlying mechanism.Methods:the myocardial infarction model was established by ligating the left anterior descending coronary artery in rats.The rats were randomly divided into model group,high-,medium-,and low-dose Lianxia formula granule groups and metoprolol group.After 30 days of intervention,the expressions of TH,NGF/TrkA/PI3K/AKT signaling pathway key proteins and mRNA in the marginal zone of myocardial infarction were detected by Western blot and RT-PCR.The distribution of TH nerve fibers was detected by immunohistochemical staining.Result:(1)TH protein and TH mRNA expression:compared with sham group,TH protein and TH mRNA were significantly increased in model group(P<0.01).Compared with the model group,TH protein and TH mRNA in Lianxia formula granule groups and metoprolol group were significantly decreased(P<0.01).(2)Immunohistochemical TH expression and distribution:Compared with the sham group,the TH-positive nerve fibers in the model group were significantly increased,the shape was coarse,the distribution was disordered,and some clustered into bundles.The average optical density of the TH positive expression in the model group was significantly increased(P<0.01).The expression of TH in Lianxia formula granule high,medium and low dose groups and metoprolol group was reduced.Compared with the model group,the average optical density of TH positive expression in Lianxia formula granule high,medium and low dose group and metoprolol group was significantly reduced(P<0.01).(3)Arrhythmia incidence:Electrophysiological experiments showed that compared with the sham group,the arrhythmia incidence of the model group increased significantly(P<0.01).Compared with the model group,the incidence of arrhythmia in the Lianxia formula granule high-dose group and metoprolol group were reduced(P<0.01,P<0.05).The arrhythmia induction rate of the Lianxia formula granule medium and low-dose groups has a decreasing trend,but there is no statistical difference compared with the model group(P>0.05).(4)NGF/TrkA/PI3K/Akt signaling pathway mRNA expression:compared with the sham operation group,the expression of NGF and TrkA mRNA in myocardial tissue of the model group was significantly increased(P<0.01).Compared with the model group,the mRNA expressions of NGF and TrkA in high-dose Lianxia formula granule group and metoprolol group were significantly decreased(P<0.01),and the mRNA expressions of NGF and TrkA in medium dose Lianxia formula granule group were decreased in different degrees(P<0.01,P<0.05),but there was no significant difference in low-dose Lianxia formula granule group(P>0.05).Compared with sham operation group,the expressions of PI3K mRNA and Akt mRNA were significantly increased in the model group(P<0.01).Compared with the model group,the expressions of PI3K mRNA and Akt mRNA in Lianxia formula granule high and medium dose groups and metoprolol group were significantly decreased(P<0.01).The expression of PI3K mRNA and Akt mRNA in low-dose Lianxia formula granule group decreased significantly(P<0.05).(5)NGF/TrkA/PI3K/Akt pathway key protein expression:compared with the sham group,the expression of NGF and TrkA protein in the model group was significantly increased(P<0.01).Compared with the model group,the protein expressions of NGF and TrkA were significantly decreased in Lianxia formula granule high-dose group,middle dose group and metoprolol group(P<0.01),and the protein expressions of NGF and TrkA in Lianxia formula granule low-dose group were decreased in varying degrees(P<0.01,P<0.05).Compared with sham group,the expression of P-PI3K protein,P-AKT protein and P-BAD in model group was significantly increased(P<0.01).Compared with the model group,the expressions of P-PI3K protein,P-AKT protein and P-BAD protein in Lianxia formula granule groups and metoprolol group were significantly decreased(P<0.01).Conclusion:Lianxia formula granule can improve sympathetic nerve remodeling in rats with myocardial infarction,and its mechanism may be related to the regulation of NGF/TrkA/PI3K/AKT signaling pathway. |
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