Experimental Study On The Effect Of Qishen Yiqi Dripping Pills On Inflammation In Rats With Heart Failure And On Activation Of RAAS System

Objective:To discuss by molecular biology technology, on the basis of symptoms of heart failure, aided by animal model,the function and effect of Chinese traditional medicine on inflammation and RAAS system activation during treating heart failure, in expectation of comprehensively sorting multi targets pharmacological mechanism preventing and combating cardiovascular disease by suppressing inflammation and RAAS system activation with Chinese traditional medicine,in order to provide theoretic foundation for further predicting single herb and compound target group.To discuss pharmacological mechanism of the compound Chinese medicine, Qishen Yiqi Dripping Pills and predict the effect of the compound on inflammation and the pathway of RAAS system activation, thus providing new ways of thinking for predicting Chinese herbal compound target and investigating its pharmacological mechanism by intervening the time window of Qi-deficiency-blood-stasis of the model with Qishen Yiqi Dripping Pills which has proved to be effective in clinical treatment.Methods:1. Rat model with heart failure caused by myocardial infarction because of coronary disease was made by left coronary artery ligation. After the ligation Qishen Yiqi Dripping Pills was taken.2. The time window of Qi-deficiency-blood-stasis of the rat model was intervened by Qishen Yiqi Dripping Pills. Its pharmacological mechanism was evaluated comprehensively.3. Key joint molecules closely related to pharmacological mechanism of heart failure and found in some documents were tested by using molecular biology technology like Western blotting to reveal mechanism of treating heart failure by mutual interaction and combined regulation of key joint molecules and different subtypes of channel protein, and thus to clarify the pharmacological mechanism treating heart failure in multiple targets and ways with the compound.Results:1. Echocardiography showed that Qishen Yiqi Dripping Pills could effectively suppress enlarged LVEDs, increase EF, and thus improve heart function.For arterial hemodynamics, Qishen Yiqi Dripping Pills could obviously improve arterial SBP and DBP. For ventricular hemodynamics, Qishen Yiqi Dripping Pills could upregulate LVEDP, Max dp/dt and Min dp/dt of rat with heart failure, thus improveventricular hemodynamics of the rat with heart failure.2. As to the expression of inflammation factors, obvious decrease of inflammation factor TNF-α,IL-6 level was observed in serum due to Qishen Yiqi Dripping Pills. Detection of RAAS relevant index showed both Qishen Yiqi Dripping Pills and Captopril could reduce AngⅡ concentration in different degrees3. Treatment of inflammation of rat with heart failure showed obvious decrease in the expression levels of the important signal transduction proteins such as JAK1, STAT3, NF-κB, AMPK in the mechanism due to Qishen Yiqi Dripping Pills, indicating Qishen Yiqi Dripping Pills can suppress relevant signal transduction pathway in some degree and thus slower the process of ventricular remodeling. Treatment of RAAS system activation of rats with heart failure showed that Qishen Yiqi Dripping Pills could obviously reduce the expression level of Angll in heart tissues, down-regulate AT1 receptor, increase the content of protective receptor AT2, up-regulate the expression of PGC1-α and also could down-regulate key channel protein AKT mediating myocardial hypertrophy.Conclusion:1. Qishen Yiqi Dripping Pills can prevent ventricular remodeling and heart failure from occurring, developing and deteriorating in multiple targetsand ways not only by suppressing the expression level of inflammation factor TNF-α, IL-6 level (by anti-inflammatory), but also suppressing relevant important signal transduction proteins such as JAK1-STAT3, AMPK and NF-KB at the same time.2. Qishen Yiqi Dripping Pills can prevent ventricular remodeling and heart failure from occurring, developing and deteriorating in multiple targetsand ways not only by effectively suppressing the expression level of Angll in heart tissues, down-regulating AT1 receptor, increasing the content of protective receptor AT2,and up-regulating the expression of PGC1-α to release ventricular remodeling, but also by suppressing the expression of relevant important signal transduction proteins AKT at the same time.3.Inflammation and RAAS system activation can not only respectively induce ventricular remodeling but also accelerate the process of ventricular remodeling by the interaction of JAK1-STAT3 and NF-κB.Qishen Yiqi Dripping Pills proves to be effective on multiple aspects and targets of heart failure, able to prevent and delay ventricular remodeling, reduce relapse of heart failure and delay the course of heart failure.