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Research BackgroundHeart failure is the clinical end stage of various cardiovascular diseases.With the increasing proportion of the middle-aged and elderly population in the world and the advancement of medical care,the prevalence of heart failure has also increased year by year.This situation exists not only in developed countries,but also in developing countries.More than half of heart failure patients are diastolic heart failure(DHF),and the prevalence rate is still rising at a rate of 1%year-on-year.It is known that there is no significant difference in the prognosis between DHF and systolic heart failure(SHF).However,However,there are no clear and effective treatments and drugs in clinical practice currently,the main ones are empirical and symptomatic treatments.Therefore,it is of great scientific significance and practical value to find effective therapeutic methods and drugs for DHF,and it is also a key and difficult point to overcome in clinical practice.Many studies show there is abnormal calcium transport and regulation at DHF.It is known that systolic and diastolic cardiomyocytes are a process of calcium circulation,including calcium release,calcium recapture,and calcium storage.If any one of these parts is abnormal will causes the destruction of myocardial calcium homeostasis and affects the systolic and diastolic function of the myocardium.At the same time,calcium transport during myocardial relaxation,such as sarcoplasmic reticulum uptake of Ca2+and phosphorylation of phosphoprotein,all require energy consumption.The "qi" of traditional Chinese medicine and the "energy" of modern biology are common in theory,and energy metabolism disorder is probably one of the essence of qi deficiency syndrome.Previous studies have also shown that the improvement of diastolic and systolic function by qi-invigorating and blood-activating drugs may be related to the regulation and maintenance of normal calcium transport in cardiac myocytes.Therefore,on the basis of summarizing clinical experience and pre-research,we have proposed the hypothesis of using Boost qi and invigorate blood methods and its representative formula—Buyang Huanwu Decoction,to treat DHF,and that Ca2+ transport regulatory protein may be its potential drug targets.? Research objectiveUsing Buyang Huanwu Decoction to Intervene in DHF Model Rats,investigating the effect of Buyang Huanwu decoction on left ventricular diastolic function in DHF rats,detecting calcium transporter expression and transcription of its mRNA,initial exploration potential drug targets for Buyang Huanwu decoction.?Research methodsRats were randomly divided into sham group and model group,use abdominal aortic constriction to establish DHF rat model.After 10 weeks,the model rats were divided into model group,western medicine group and Chinese medicine group.After 8 weeks,rats with successful modeling were divided into model group,western medicine group and Chinese medicine group.After drug administration,Chinese herbal medicine group:Buyang Huanwu Decoction 12.72g/(kg·d),western medicine group:metoprolol tartrate 0.0045g/(kg·d),sham operation group and model control group were given equal amounts of deionized water.Each group was administered once daily.After the drug intervention was completed,Using echocardiography to measure the peak velocity of E waves in early diastole of left atrioventricular valve diastole(E)and the peak velocity of late A wave in the late diastole(A),and calculate the E/A ratio,early mitral annular diastolic movement speed(e'),mitral annulus Diastolic late movement speed(a'),and calculate e'/a',E/e' ratio;The protein expression of calcium pump(SERCA2a)and phospholamban(PLB)on sarcoplasmic reticulum was detected by Wstern blot.Using polymerase chain reaction(PCR)detected SERCA2a,PLB,RyR2,and L-type calcium channel's mRNAs.?Research results1.Echocardiographic results:E/A and e'/a' values in the model group were lower than those in the sham group(p<0.05),and E/e' was higher(p<0.05).The e'/a' of the Chinese medicine group was higher than that of the model group(p<0.05),and there was no significant difference between the Chinese medicine group and the western medicine group2.Western blot results:The protein expression of SERCA2a and PLB in the myocardium of the model group was lower than that in the sham group(p<0.05).While the protein expression of SERCA2a and PLB in the myocardium of the western medicine group and the traditional Chinese medicine group rats was higher than that of the model group(p<0.05),and there was no significant difference in the expression of these two proteins between the Chinese medicine group and the western medicine group(p>0.05).3.The results of PCR:There was no difference in mRNA transcription of L-type calcium channels in each group(p>0.05).The mRNA of RyR2 in model group and traditional Chinese medicine group was lower than that in sham group(p<0.05).Western medicine group's RyR2 mRNA transcription and sham group's had no significant difference(p>0.05),There was no significant difference in RyR2 transcription amount between the western medicine group and the Chinese medicine group compared with the model group.The mRNA transcription of SERCA2a and PLB in model group,traditional Chinese medicine group,and western medicine group were all lower than the sham group(p<0.05).Compared with the model group,mRNA transcription of SERCA2a and PLB was higher in the western medicine group and the traditional Chinese medicine group(p<0.05),there was no significant difference between the Chinese medicine group and the western medicine group(p>0.05)in the above results.?.Conclusions1.Calcium Transporter Expression and mRNA Transcription Decrease in SERCA2a and PLB in DHF Rats2.Boost qi and invigorate blood methods and its representative formula—Buyang Huanwu Decoction can improve left ventricular diastolic function in DHF rats to some extent.3.Buyang Huanwu Decoction may regulate the diastolic function of DHF rat left ventricle by increasing protein expression and mRNA transcription of SERCA2a and PLB. |
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