Corydalis Extract The Mechanism For The Treatment Of Coronary Artery Disease Ventricular Arrhythmias

1.1 To systematically review the effect and safety of Chinese medical treatment of coronary heart disease (CHD) patients with ventricular premature complexes (VPC), so as to provide evidence for Chinese medicine treating CHD patients with VPC.1.2 Using the data mining technology to dig the data base "CHD platform of integrated clinical and scientific research", to investigate diagnose and treatment regularity of Chinese medicine treating CHD patients with VPC, and to explore the prescription and medication features.1.3 From the aspects of proteomics, enzymology and immunohistochemical morphology, to explore the mechanism of Yanhusuo extract (YE) on rat model of ventricular arrhythmia (VA) after acute myocardial infarction (AMI), so as to provide experimental evidences for YE preventing ventricular arrhythmia from CHD, especially from AMI, and settle the foundation to explore the new medicine of YE.2. Methods2.1 Methods of systemic reviewDatabases of PubMed, CBM, CMCC, VIP, CNKI and WanFang were searched for all available data till February 2011. RevMan5.1.4 software was used to conduct meta-analysis. Jadad score was used to assess the quality of the included trials.2.2 Methods of data miningThe data change-over and data loading for demography information general clinical characteristic,syndromes,therapeutic methods and Chinese medicine prescription were managed by SQL Server 2000 software. Multi-subject inquest and web analysis for the request of clinical need of VA in CHD were managed by Business Objects software. The syndromes distribution and TCM prescription of VA in CHD were dug and analyzed by Oracle 10g software. The Chinese medicine compatibility regularity and the relationship between Chinese medicine and syndromes were explored by complex networks analysis.2.3 Methods of experimental research for YE treating VA after AMI in ratsTo establish rat model of AMI, Wistar rats were randomly divided into normal group, sham group, model group, metoprolol group, Shensong Yangxin Capsule (SYC) group and low dosage,median dosagee and high dosage of YE groups. The infarction area was measured by N-BT staining. The Na+-K+-ATPase and Ca2+-ATPase activities were measured by ELASA method. Western Blot method was used to measure the protein levels of connexin43 (CX43) and phosphor-CX43 (P-CX43), and immnohistochemical method was used to observe the expression location of CX43 and P-CX43. From above all aspects to explore the mechanism of YE on rat VA model after AMI.3. Results3.1 Results of systematic review---the effect of Chinese medicine on CHD patients with VPC, a meta-analysis.Compared with blank control group or western medicine group, Chinese medicine might treat CHD patients with VPC effectively, and also might reduce the VPC frequency (P<0.05). According to Jadad score, the quality of most of the trials was low.3.2 Results of data mining analysis386 CHD patients with VA aged 70.06±10.33 years in average were enrolled, including 201 males and 185 females. The subtypes and combined diseases were hypertension, heart failure, angina pectoris, old myocardial infarction,and diabetes mellitus. The main syndromes of CHD patients with VA were blood stasis, qi deficiency and phlegm-turbid. The first TCM prescription after admission mainly contained Fuling, Danshen, Danggui, Banxia, Maidong, Gancao, Honghua, Chuanxiong, Taoren, and Chenpi. The main functions of these Chinese medicines above were tonifying qi, activating blood and regulating qi. The main anti-arrhythmia medicines were metoprolol, amiodarone and mexiletine. The prognosis of CHD patients with VA was worse than the other types of CHD patients with arrhythmia, the ineffective ratio and mortality were much higher. The complex netmork analysis of medicine-syndrome showed that the main syndromes of CHD patients were qi deficiency, blood stasis and phlegm-turbid. The corresponded medicines for treating the main syndromes were Danshen, Fuling, Danggui, Maidong, Chishao, Honghua, Chuanxiong, Gancao, Banxia, Taoren, Chenpi and Wuweizi.3.3 Results of experimental research into YE treating VA after AMI in rats3.3.1 Result of myocardial infarction areaCompared with the model group, low dosage and median dosage group of Yanhusuo Extract, Metoprolol group and Shensong Yangxin Capsule group could reduce the myocardial infarction area and lower the ratio of myocardial infarction area/ventricle area (P<0.05).3.3.2 Result of Na+-K+-ATPase and Ca2+-ATPase activitiesCompared with the normal group, both the Na+-K+-ATPase and Ca2+-ATPase activities in model group were lowered obviously (P<0.01). The low,median,high dosage of YE and other medicine groups could improve the level of Na+-K+-ATPase and Ca2+-ATPase activities, compared with model group (P<0.01).3.3.3 Result of protein level of CX43 and P-CX43 using Western Blot method.Compared with normal group, the protein levels of CX43 and P-CX43 in model group were obviously lowered (P<0.05). Except the high dosage of YE group, the other medical groups could improve the reduced protein levels of CX43 and P-CX43 after AMI (P<0.05). In addition, the effect of median dosage of YE group was as good as Metoprolol group.3.3.4 Result of pathomorphology in general of the rat hearts in all the groupsHematoxylin and Eosin (HE) staining showed that the low,median,high dosage of YE and other medicine groups could relieve the muscle fiber injury. Most of muscle fibers in the rat hearts of these groups were intact and line up in order. Only local fibroplasias and lymphocytes infiltrating were seen. Nevertheless, in the model group, cardiac muscle fibers lined up disorderly. Plasmolysis, fibroplasias, glassy degeneration, granulation tissue and necrotic tissue were seen.3.3.5 Result of immunohistochemical CX43 and P-CX43In the normal group, CX43 and P-CX43 were mainly located at end-to-end apposition, also known as the myocardial cell intercalated disc region. In the model group, cellular structure was destroyed; CX43 and P-CX43 expression decreased obviously, and dislocated from end-to-end to side-to-side connections, also called lateralization. Compared with model group, the expression of CX43 and P-CX43 in YE groups, Metoprolol group and Shensong Yangxin Capsule group increased obviously, and just some of the cellular structures suffered from injury. However, some cardiocytes appeared lateralization.4. Conclusion4.1 The result of systematic review suggested that Chinese medicine could treat CHD patients with VPC effectively and safely. However, much more high quality researches are still needed to back up this result. 4.2 Blood stasis, qi deficiency and phlegm-turbid were the main syndrome elements of CHD patients with VA. The most of Chinese medicine used were Danshen, Fuling, Danggui, Chishao, Honghua, Chuanxiong, Gancao, Banxia, Taoren, Chenpi, and Wuweizi. Corresponded with the main syndrome, the functions of these Chinese medicines were tonifying qi, activating blood and regulating qi.4.3 Yanhuosuo Extract could reduce the acute myocardial infarction area on rat AMI model, enhance the protective effect of ischemia injury, increase the activities of Na+-K+-ATPase and Ca2+-ATPase and the reduced protein level of CX43 and P-CX43 after AMI, and reduce the lateralization of CX43 and P-CX43, and accordingly reduce the genesis of ventricular arrhythmia. The mechanism of YE treating ventricular arrhythmia might be related to above all.