Based On The Xinkaikujiang Method In Treatise On Fevers To Study The Efect And Mechanism Of Ventricular Remodeling Mats After Myocardial Infarction

Theoretical researchOriginated from “The Inner Canon of Huangdi”,the Xinkai Kujiang method, a traditional Chinese medicine therapeutic method, was proposed in “Treatise on Exogenous Febrile Disease”, which has great influence on descendant. This therapeutic method has some functions mainly including adjusting und pivot,coordinating organs, etc, which is widely used in cold heat jumble epigastric fullness syndrome, hot cold syndrome, phlegm heat stasis syndrome, stasis and heat syndrome. It also has certain effects on the development of the theory of the spleen and stomach and the doctrine of epidemic febrile disease.Ventricular remodeling is a series of changes appeared after the occurrence of ventricular myocardial infarction including chest pain, cardiodynia and palpitations.Ancient Chinese understanding of the disease can be attributed to the six-excess external contraction, modern diet, old and feeble, and valetudinarianism. The deficient root is refers to the heart, lung, spleen, kidney and other viscera Qi, blood, yin and yang deficiency, excess in superficiality mainly refers to the phlegm, blood stasis, water wet stop together.After researching previous dynasties literature carefully and combined clinical observation for many years, the changes of the environment,lifestyle,diet, physique etc. in the modern society was considered that heat evil had a more and more important influence in this kind of disease. Based on the point of view that mutual cementation of sputum stasis and heat leaded to the development of biochemical exacerbating, research group put forward the thinking that applying of treatise of Xinkai Kujiang method on cold-induced diseases as the main method to treat this kind of disease. With the principles of Xinkai Kujiang method and combined with modern pharmacological research achievements, our research group proposed Xuan Bi San Jie Fang to treat this illness. Xuan Bi San Jie Fang had the functions of clear heat, blood, sputum polyester and centralizer. It had remarkable curative effect on clinical application and clinical research for years.The modern mechanism researches of ventricular Remodeling include the changes of haemo dynamics, neurocrine activation, inflammatory reaction, apoptosis, myocardial fibrosis, etc. Experimental researchObjectiveThe objective of this research was to explore the prevention and treatment effects of Xuanbi’sanjie, which was based on “The Methods of Xinkai Kujiang” of Treatise on cold-induced diseases, on the heat-stasis syndrome of ventricular remodeling after myocardial infarction of rats. This research would further provide scientific support on the development of new drug. Methods1.Study on the interfere of Xuan Bi San Jie Fang to rats’ disease and syndrome of ventricular remodeling with heat- stasis syndrome after myocardial infarction.Using the anterior descending coronary artery method for Wistar rats to establish model of acute myocardial infarction.Live rats can appear obvious ventricular remodeling after being fed for 4 weeks, both model group B and xuan bi Sanjie group B of rats are produced the stasis hot model by carrageen glue and active dry yeast. Observation of the ventricular remodeling is mainly adopts the method of practicein heart function and cardiac index, HE staining to observe the myocardial cell structure, Masson staining and electron microscope to observe fibrosis cell microstructure changes. Observation of the stasis heat mainly use the indicators such as the heart rate, body temperature, blood routine, serum IL-6, IL-10, the TNF alpha inflammatory factor, hemorrheology indexes.2.Study on intervention of the Xuan Bi San Jie Fang to serum inflammatory factors. Using ELISA to detect IL-6, IL-10, the TNF alpha inflammation factor in the serum to the rats model of ventricular remodeling after myocardial infarction to reveal its mechanism.3. Intervention study on the effect of Xuan Bi San Jie Fang on the rats serum fibrosis factors.Using ELISA to detect serum TGFbeta1, MMP-9 and TIMP-1, HYP fibrosis factors in the serum of the rats model of ventricular remodeling after myocardial infarction.4. Intervention study on the effect of Xuan Bi San Jie Fang on protein expression of syndrome of ventricular remodeling after myocardial infarction.Using Western blotting to detect col1, P-smad3 and smad7 factor in the cardiac tissues to all kinds of rats. Using immunohistochemical method to detect expression.5.Intervention study on the effect of Xuanbi’sanjie(XBF) on protein expression of syndrome of ventricular remodeling after myocardial infarction.Using the methods of real-time fluorescent quantitative PCR analysis to detect NF-κB, smad3, smad7, TGF- beta 1 and other factors in heart tissue to all kinds of rats. ResultsEffect on ventricular remodeling:1Heart function: Compared with the model A group, the model A group of Xuan Bi San Jie Fang can obviously increase big rat cardiac ejection fraction, but the improvement of the ventricular chamber is not obvious; Contrast with the model A group, Captopril can reduce the ventricular chamber diameter of the period of relaxation and systole, but the improvement in cardiac ejection fraction was not significant. 2Light microscope and Electron microscope test results show that the model A cardiac muscle cell showed obvious necrosis, myocardial cell swelled, inflammatory granulocyte infiltration, myocardial mitochondrial swelling. Captopri and Xuan Bi San Jie Fang could protect cardiomyocytes, relieve swelling, inflammatory cell infiltration,protecting myocardial mitochondria,visible morphological structure integrity, mitochondrial cristae increased, stroma dense and so on. 3 Studies with Masson Stained light microscope found that Captopri and Xuan Bi San Jie Fang can significantly reduce the degree of myocardial fibrosis after ventricular remodeling.The influence of syndrome:1Heart rate: Compared with the model A group, model B’s heart rate was significantly accelerated. Compared with the model B group, the model B group of Xuan Bi San Jie Fang heart rate decreased significantly. 2 Temperature: Compared with the model A group, model B group’s body temperature was significantly increased 6 hours after the injection of active dry yeast,9 hours is the most obvious. Compared with the model B group, the model B group of Xuan Bi San Jie Fang body temperature decreased significantly.3Routine blood test: Compared with the model A group, model B group hemoglobin concentration increased significantly; Compared with the model B, Xuan Bi San Jie Fang model B group red cell pressure was significantly decreased. 4Hemorheology: Compared with the model A group, model B group the whole blood viscosity in mid cut and in high cut, increased significantly; Compared with the model B group, Xuan Bi San Jie Fang model B group Whole blood viscosity low cut, middle cut, red blood cell pressure product was significantly reduced. 5Inflammatory factors in serum: Compared with the model A group, model B group Serum IL-6 and TNF- levels were significantly increased; Compared with the model B group, Xuan Bi San Jie Fang model B group IL-10 was significantly increased.Study on Mechanism:1Xuan Bi San Jie Fang has inhibitory effect on the inflammatory factors IL-6 and TNF-α in the serum of rats after myocardial infarction, but it has the function of promoting the growth of IL-10.2It has Inhibiting effect of factor TGF- β1 and MMP-9 on promoting fibrosis, but to inhibit the fibrosis of the factor TIMP-1 has promoting effect. 3The expression of P-smad3 and COL1 protein was down regulated, but up regulation of Smad7 protein expression. 4The expression of NF-κB, TGF-β1,Smad3 and RNA was down regulated, but Smad7 transcription RNA up regulation. Conclusion1. The Treatise on cold-induced diseases of Xinkai Kujiang is the principle of Xuan Bi San Jie Fang,and it has effective treatment and improvement on the ventricular remodeling and stasis heat stasis heat syndrome rat ventricular remodeling after myocardial infarction.2.Xuan Bi San Jie Fang can down and inhibit the NF-κB、IL-6、TNF-α which inflammatory factors that cause ventricular remodeling, it has promoting effect on the L-10 of the inflammatory inhibitor, it can inhibit the inflammation and immune response induced by IL-6 and other inflammatory factors, which are mediated by NF-κB in general. Therefore, it will have a better prevention and treatment of ventricular remodeling and stasis heat syndrome.3.Xuan Bi San Jie Fang can down and inhibit the TGF-β1、MMP-9、COL1,smad3、P-smad3 which fibrosis factors that cause ventricular remodeling, it has promoting effect on the TIMP-1、 smad7 of fibrosis factors, and the reaction of the TGFβ1-smad pathway may play a role in the prevention and treatment of ventricular remodeling.4.Based on the “pungent open and bitter down bearing” of “Treatise on cold-induced diseases”, the Xuan Bi San Jie Fang may be acting on the NF-κB pathway to eliminate the inflammatory responses in the process of ventricular remodeling. And it can act on TGFβ1- Smad pathway to ease fibrosis, at the same time, it can obviously prevent and cure the syndrome of blood stasis in the ventricular remodeling. It shows that these two pathways are related to blood stasis.