| Ischemic heart disease is a serious threat to human health, with which morbidity andmortality gradually increased in recent years. Its pathology is characterized by a narrowingor blockage of myocardial blood vessels, leading to myocardial infarction.In TraditionalChinese medicine, ischemic heart disease is in the case of "Chest pain","heartache" areas,and Qi deficiency with blood stasis, poor context is the key to its pathogenesis[1,2].Thoughreperfusion therapy after acute myocardial infarction may restore the blood supply of theischemic tissue, rescue outstanding necrosis ischemic tissue effectively,itˊs limited to thetime of revascularization in ischemic tissue and reperfusion injury.Therefor, therapeuticvascular regeneration become a new hotspot for treatment of myocardial infarction, inwhich Chinese medicine has played an important role[3]. The group side “Yiqihuoxue” hasa positive role in therapeutic angiogenesis,but its mechanism on vascular maturation andprescription principle is unclear. Yiqihuoxue compound Qidan Tongmai tablet (QDTMT)completed by modern pharmaceutical preparation process according to the prescriptions of Chinese traditional medical theory and clinical observations,is composed byMilkvetchRoot（Huangqi）、Radix Salviae Miltiorrhiza（Danshen）、Chinese Angelica(Danggui)、Carthamus tinctorius (Honghua)、Cassia twig (Guizhi).QDTMT has Yiqihuoxue, Tongmaianalgesic efficacy,and is effective prescription for the treatment of ischemic heartdisease.Preliminary studies shows that QDTMT could reduce blood viscosity, mitigatemyocardial ischemia-reperfusion injury and improve cardiac function after myocardialinfarction[4-8]. However, its mechanism in improving heart function after myocardialinfarction is not fully understood.It will induce a series of inflammatory response after myocardial infarction, of whichinflammatory mediators would promote the occurrence of ventricular remodeling, leadingto cardiac hypertrophy, interstitial remodeling of collagen deposition, myocardialfibrosis.Fibrosis is a direct result of reduced diastolic function, which progressed to heartfailure[9,10].In this process, the inflammatory cytokines such as tumor necrosis factor-alpha(TNF-α), myocardial fibrosis-related factors such as transforming growth factor-β1(TGF-β1,), type I collagen(Col1), type III collagen (Col3)[11-13]and the contentofhydroxyproline (HYP)[13][14]in the tissue are closely related to the degree of myocardialfibrosis in the non-infarcted area after myocardial infarction, and they can affect therecovery of post-infarction heart function.And then, QDTMT improves cardiac function after myocardial infarction whetherrelated to the inhibition of myocardial fibrosis of non-infarcted area and affectingventricular remodeling? Currently, the prevailing view is that, after myocardial infarction,therapeutic angiogenesis can accelerate the establishment of collateral circulation,increasethe ischemic myocardial perfusion,promote the recovery of hibernatingmyocardium,improve myocardial fibrosis, and thus reverse ventricular remodeling.Sowhether QDTMT could inhibit myocardial fibrosis and ventricular remodeling bypromoting angiogenesis and vascular maturation of non-infarcted area?"Lingshu evil off chapter" says" Cases of gas accumulates in the chest,out of thethroat to perfuse the coronary artery and conduct breathing."Cases of gas accumulates inthe chest,purfuses the cornary and promotes Qi and blood running. Clear air inhaled by the lung which affects the filling or otherwise of the cases of gas is an important part of thegas generated.The lack of clear air leads to the deficiency of the cases of gas，and hypoxiatolerance is as one of the important basis for the evaluation of qi deficiency for the heart.The Yiqihuoxue drug has a role to improve the body’s resistance to hypoxia.HIF-1α is akey transcription factor of the body’s response to hypoxia environment, and oxygenconcentration can regulate the expression of HIF-1α.Based on the intrinsical link betweenthe cases of gas and oxygen,and the common anti-hypoxia effect by Yiqihuoxue andHIF-1α,we speculate that the the response and regulatory mechanism of HIF-1α in thehypoxic environment may be highly relevant with Yiqihuoxue mechanisms.In hypoxicconditions, HIF-1α (hypoxia induced factor-1α) signal is one of the key signalingmolecules of angiogenesis and vascular maturation in the body oxygen responseregulation[11,15],and it＇s also the critical transcription factor in therapeutic angiogenesisand vascular stability. As a critical downstream factor of angiogenesis mediated byHIF-1α[12],VEGF (vascular endothelial growth factor)can promote endothelial cellproliferation, migration and prevent endothelial cell apoptosis.However, VEGF stimulatedthe formation of new blood vessels alone showed an incomplete and leaky form[13].Todevelopment for a mature and stable vascular,the neovascularization need for endothelialcell proliferation and invasion,also dependent on the raising and covering by the vascularsmooth muscle cells and pericytes.Some studies have shown that the neovascularizationinduced by the overexpression of HIF-1α is similar to normal vessels on structure andfunction, and there is novascular leakage phenomenon[14].Then, how dose HIF-1α expressin ischemic myocardium? whether or not the compound of Yiqihuoxue could promotevascular maturation,and is associated with HIF-1α of its influence on the mechanisms ofangiogenesis and vascular maturation? To further explain the role played by the theYiqihuoxue and HIF-1α signaling molecule in the process of myocardial infarction, theexperiment was conducted for a preliminary study of its mechanism.Objective: This study was designed on the model of myocardial infarction SD rat gavagedby QDTMT by observing the characterization of Qi deficiency and Blood stasis,cardiacfunction, myocardial phlegmonosis, myocardial fibrosis,angiogenesis and vascular maturation to assess the role of Yiqihuoxue played in the process of myocardialinfarction;Observe the expression of inflammation-related molecules and myocardialfibrosis-related molecules to assess the impact of QDTMT on cardiac function;Detect theexpression of HIF-1α and VEGF signaling molecules, to explore whether they can withYiqihuoxue collaborativly regulate the body’s oxygen response, affect angiogenesis andvascular maturation.Methods:(1)establish the myocardial infarction model of rats and carry out a series ofbasic evaluation.(2) Measure the myocardial inflammation and myocardial fibrosis of rats byhistopathological methods.(3)Detect the expression of inflammation-related factors and myocardial fibrosis factor ofrats.(4) Immunohistochemistry was used to detect angiogenesis in non-infarcted area.(5)Detect the expression of HIF-1α and VEGF during different periods(6) Detect neovascular maturation by double immunofluorescence.Results:(1)QDTMT can significantly improve the rat physiological characterization andthe base case.(2)QDTMT can inhibit inflammation and fibrosis in rats with myocardial infarction,reverse ventricular remodeling.(3)QDTMT can increase microvascular number and density of the non-infarcted area inrats of myocardial infarction.(4)QDTMT is able to promote the expression of HIF-1α and VEGFmRNA at a certainperiod of time.(5)QDTMT can promote neovascularization maturation of the non-infarcted area.Conclusion: Yiqihuoxue compound QDTMT could promote the myocardial angiogenesisand maturity of the non-infarcted area of myocardial infarction in rats by promoting theexpression of HIF-1αand further regulating the expression of VEGF, improve myocardialblood supply and oxygen supply, suppress inflammation and myocardial fibrosis, reducethe degree of ventricular remodeling,and improve cardiac function and the characterization of Qi deficiency and Blood stasis in rats.it supplies a new treatment ideafor the treatment of ischemic heart disease. |
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