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Objective:To observe the effect of total flavonoids from Epimedii Folium （TEF） on the angiogenesis of ischemic myocardium in rats after acute myocardial infarction （AMI） and discuss its molecular biological mechanism of attenuating myocardial ischemia and improving cardiac function. Method:AMI in rats was induced through the ligation of left anterior descending coronary artery. All male SD rats were randomized into sham-operated group， model group， diltiazem group （10 mg·kg<sup>-1</sup>·d<sup>-1</sup>）， and TEF low-dose and high-dose groups （100 and 200 mg·kg<sup>-1</sup>·d<sup>-1</sup>）， with 8 rats in each group. After modeling， rats in the diltiazem group and TEF groups were given corresponding doses of diltiazem and TEF， respectively， and those in the model group and sham-operated group received normal saline of equivalent volume， once a day for 7 days. After the administration， VisualSonics Vevo2100 imaging system was used to detect the cardiac structure and function and hematoxylin-eosin （HE） staining to observe the histomorphological changes in myocardial ischemic area. Immunohistochemistry was employed to analyze the expression of CD31 and <italic>α</italic>-smooth muscle actin （<italic>α</italic>-SMA） in ischemic myocardium and Western blot to detect the expression of vascular endothelial growth factor-receptor 2 （VEGF-R2） and phosphorylation of protein kinase B （Akt） in ischemic myocardium. Real-time PCR was applied to quantify the mRNA levels of vascular endothelial growth factor （VEGF） and basic fibroblast growth factor （bFGF）. Result:Compared with the sham-operated group， the model group demonstrated significant increase in left ventricular systolic diameter （LVIDs）， left ventricular internal diameter at end-diastole （LVIDd）， left ventricular end-systolic volume （LVEVs）， and left ventricular end-diastolic volume （LVEVd）， significant decrease in End-systolic thickness of left ventricular anterior wall （LVAWs）， end-diastolic thickness of left ventricle anterior wall （LVAWd）， end systolic thickness of left ventricular posterior wall （LVPWs）， stroke volume （SV）， ejection fraction （EF）， fractional shortening （FS）， and cardiac output （CO）， obvious pathological changes in the ischemic myocardium， and plummet of the expression of CD31 and <italic>α</italic>-SMA （<italic>P</italic><0.01）， Akt phosphorylation level， protein level of VEGF-R2， and mRNA levels of VEGF and bFGF （<italic>P</italic><0.05， <italic>P</italic><0.01）. High-dose TEF significantly alleviated the pathological changes of ischemic myocardium as compared with the model group. Moreover， TEF high-dose group showed significantly lower levels of LVIDs， LVIDd， LVEVs， and LVEVd， significantly higher levels of LVAWs， LVAWd， LVPWs， SV， EF， FS， and CO， higher expression of CD31 and <italic>α</italic>-SMA （<italic>P</italic><0.05， <italic>P</italic><0.01）， and higher levels of VEGF-R2 protein， phosphorylated Akt， and VEGF and bFGF mRNA than the model group （<italic>P</italic><0.05， <italic>P</italic><0.01）. Conclusion:TEF can effectively improve myocardial perfusion in peri-myocardial infarction area and attenuate ventricular remodeling and heart failure after AMI by up-regulating the expression of bFGF， VEGF， and VEGF-R2 in ischemic myocardium following AMI and activating phosphatidylinositol 3-kinases （PI3K）/Akt/VEGF signaling transduction pathway which can promote angiogenesis in ischemic myocardium.
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Objective:To investigate the effect of Shuangshen Ningxin capsules （SSNX） on cardiac hemodynamics and cardiac function in rats with coronary microvascular dysfunction. Method:Rats were randomly divided into a sham operation group， a model group， a nicorandil group （5 mg·kg<sup>-1</sup>）， and high- （180 mg·kg<sup>-1</sup>）， medium- （90 mg·kg<sup>-1</sup>）， and low-dose （45 mg·kg<sup>-1</sup>） SSNX groups. Rats received corresponding drugs for 7 days. Two hours after the last administration， the model of coronary microvascular dysfunction was induced by left ventricular injection of embolic microspheres （40-120 μm， about 1 000 microspheres）. Twenty-four hours after modeling， left ventricular internal dimension in diastole （LVIDd）， left ventricular internal dimension in systole （LVIDs） left ventricular end-diastolic volume （LVEDV）， left ventricular end-systolic volume （LVESV）， stroke volume （SV）， cardiac output （CO）， left ventricular ejection fraction （EF）， and left ventricular shortening rate （FS） were detected by echocardiography. Cardiac catheterization was used to observe the arterial systolic blood pressure （SBP）， diastolic blood pressure （DBP）， left ventricular systolic pressure （LVSP）， left ventricular end-diastolic pressure （LVEDP）， maximum rate of increase in left ventricular pressure （LV+dp/dt<sub>max</sub>）， and maximum rate of decrease in left ventricular pressure （LV-dp/dt<sub>max</sub>）， and the mean arterial pressure （MAP） was calculated. Heart rate （HR） was calculated according to Ⅱ lead ECG. Biochemical analysis was carried out to detect the activities of creatine kinase （CK）， creatine kinase-MB （CK-MB）， and lactate dehydrogenase （LDH）. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum cardiac troponin T （cTnT）. Western blot was used to detect the protein expression of Caspase-3， Bcl-2， and Bax， and 2，3，5-triphenyltetrazolium chloride （TTC） staining to observe the area of myocardial infarction. Hematoxylin-eosin （HE） staining was used to observe the morphological changes of the myocardium. Result:As revealed by echocardiography， compared with the sham operation group， the model group showed reduced SV， CO， EF， and FS （<italic>P</italic><0.01）， and increased LVIDs and LVEDV （<italic>P</italic><0.01）. Compared with the model group， the SSNX groups showed increased EF （<italic>P</italic><0.05， <italic>P</italic><0.01） and FS （<italic>P</italic><0.01）， and the high- and medium-dose SSNX groups displayed reduced LVIDs and LVESV， and increased LVEDV， SV， and CO （<italic>P</italic><0.05， <italic>P</italic><0.01）. SBP， DBP， MAP， LVSP， LV+dp/dt<sub>max</sub>， and LV-dp/dt<sub>max</sub> in the model group were lower than those in the sham operation group （<italic>P</italic><0.01）， while there was no significant difference in HR. SSNX improved hemodynamics of rats， and increased SBP， DBP， MAP， LVSP， LV+dp/dt<sub>max</sub>， LV-dp/dt<sub>max</sub>， and HR as compared with the model group （<italic>P</italic><0.05， <italic>P</italic><0.01）. The serum CK， LDH， CK-MB， and cTnT levels in the model group were higher than those in the sham operation group （<italic>P</italic><0.01）. Compared with the model group， SSNX groups reduced serum CK， LDH， CK-MB， and cTnT （<italic>P</italic><0.05，<italic> P</italic><0.01）. Compared with the sham operation group， the model group displayed increased expression of Caspase-3 protein in the myocardium （<italic>P</italic><0.01） and reduced expression of Bcl-2 protein （<italic>P</italic><0.05）. The expression of Caspase-3 protein in the myocardium of SSNX groups was lower than that in the model group， and statistical difference was observed between the low-dose SSNX group and the model group （<italic>P</italic><0.05）. Compared with the model group， the SSNX groups exhibited increased expression of Bcl-2 in the rat myocardium， and the statistical difference was observed in the high-dose SSNX group <italic>（P</italic><0.01）. As demonstrated by the TTC staining， compared with the model group， SSNX groups showed reduced areas of myocardial infarction （<italic>P</italic><0.01）. The HE staining indicated that the pathological injury in myocardial tissues of the SSNX groups was relieved as compared with that in the model group. Conclusion:SSNX can significantly enhance the cardiac function after coronary microvascular dysfunction caused by embolic microspheres， improve cardiac hemodynamics， reduce the area of myocardial infarction， and decrease CK， LDH， CK-MB， and cTnT levels. The mechanism may be related to the inhibition of cardiomyocyte apoptosis to protect the myocardium.
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Objective:To investigate that the effect of ethanol extracts from Sophorae Tonkinensis Radix et Rhizoma on the expression of transforming growth factor-β1 (TGF-β1)and Smad3 in the hypertrophic scars of rabbit ears and elucidate its mechanism to improve hypertrophic scars. Method:The model of hypertrophic ear scar model was established by damaging the inner skin of ears in New Zealand white rabbits.The 49 rabbits were randomly divided into control group, model group, low, medium and high-dose ethanol extracts groups from Sophorae Tonkinensis Radix et Rhizoma (0.4，1.0，2.0 g·kg-1), asiaticoside ointment group(5 mg·kg-1) and compound heparin sodium allantoin gel group(20 mg·kg-1), 7 rabbits per group. Except control group, the different drug about 0.5 mL had been applied the hypertrophic scar of rabbit ears once a day. After 42 days, the tissues of hypertrophic scar were obtained. Hematoxylin-eosin（HE）staining was used to observe the pathological changes of rabbit ear scar tissue and determine the scar hyperplasia index. The expression of TGF-β1 and Smad3 in scar tissue of rabbit ears were detected by immunohistochemistry, Western blot and reverse transcription PCR（RT-PCR）. Result:Compared with control group, the pathological changes of the ear scars in the model group showed obvious hyperplasia and higher hyperplasia index (P<0.01). Meanwhile, the expressions of TGF-β1 and Smad3 in scar tissue of rabbit ears were significantly increased (P<0.01). Compared with model group, the pathological structures of the ear scar tissue were significantly improved and the hyperplasia index of ear scar tissue was clearly reduced in medium and high-dose groups of ethanol extracts from Sophorae Tonkinensis Radix et Rhizoma(P<0.05，P<0.01). The protein and mRNA expression of TGF-β1 and Smad3 in scar tissue were also decreased in different group of ethanol extracts from Sophorae Tonkinensis Radix et Rhizoma compared with the model group (P<0.05，P<0.01). Conclusions:Ethanol extracts from Sophorae Tonkinensis Radix et Rhizoma may play a curative role in inhibiting hypertrophic scars by reducing the expression of TGF-β1 and Smad3 in scar tissue and inhibiting the TGF-β1/Smads signal transduction pathway. These provides the experimental basis for the clinical application of Sophorae Tonkinensis Radix et Rhizoma in the treatment of hypertrophic scars.
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Objective:To investigate the therapeutic effect of Qihong capsule on pentobarbital sodium induced heart failure in beagle dogs. Method:Thirty healthy adult beagle dogs were randomly divided into 6 groups, 6 in each group. They were normal group, model group, digoxin tablet group (40 μg·kg-1), Qihong capsule high, medium and low dose groups (2.6，1.3，0.65 g·kg-1). The heart failure model of beagle dogs was established by intravenous infusion of 2% pentobarbital sodium. The success standard of the model was that the maximum rate of rise of left ventricular pressure was reduced by 70%.The corresponding drugs were given through duodenum. The Ⅱ lead electrocardiogram, coronary blood flow, cardiac output, left ventricular pressure and maximum rate of left ventricular pressure rise were measured by multi-channel physiological recorder. The arterial oxygen content and coronary sinus oxygen content were measured by Roche blood oxygen analyzer at different time points, and the myocardial oxygen utilization rate was calculated. Result:After intravenous infusion of 2% pentobarbital sodium for about 15 minutes, beagle dogs began to show obvious symptoms of heart failure. The main manifestations were the increase of PR interval of Ⅱ lead electrocardiogram, the decrease of coronary blood flow, left ventricular pressure, cardiac output, cardiac output, venous oxygen content, and the increase of myocardial oxygen utilization rate (P<0.01) compared with the model group, Qihong capsule significantly increased coronary blood flow at 60-120 min after treatment (P<0.05). The cardiac output of 2.6 g·kg-1 Qihong capsule increased significantly at 45-60 min after treatment, with the maximum increase of about 16%, which was significantly different from that of model group (P<0.05). At the same time, it can increase the oxygen content of coronary sinus blood, which indicates that the myocardial oxygen supply is increased and the oxygen utilization rate is decreased. Qihong capsule 1.3 g·kg-1 group significantly increased the maximum rate of left ventricular pressure rise (P<0.05), the maximum increase rate was about 42%. Conclusion:Qihong capsule can increase coronary blood flow and venous blood oxygen content at the same time, make myocardial nutrient supply sufficient, reduce oxygen utilization rate, on this basis, Qihong capsule can further increase cardiac output and improve cardiac function, so as to play a protective role in heart failure.
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Objective: To observe the intervening effects of Tongmai Yangxin Pills on miniature pigs with syndrome of deficiency of both qi and yin in later stage of myocardial ischemia reperfusion injury. Methods: A total of 24 miniature pigs were randomly divided into the sham-operated group, the model group (syndrome of deficiency of both qi and yin in myocardial ischemia), the Shengmai Capsules group (0.14 g/kg), and Tongmai Yangxin Pills groups (0.36 g/kg) with six pigs in each group. Except for the sham-operated group, the left anterior descending artery in other groups had been occluded for 30 min by inflation balloons and arterial reperfusion injury was acquires by withdraw balloons. After the operation, the groups were administered with drugs for four weeks. The parameters of noninvasive hemodynamics were measured at the end of study. The tongue color was recorded by digital camera. The tongue and pulse manifestation of the miniature pigs were evaluated according to the symptom-graded scoring method. The size of myocardial ischemia and infarction was analyzed by Evens and TTC staining. Results: Compared with the sham-operated group, the area of myocardial ischemia and necrosis in the model group increased significantly. The noninvasive hemodynamics showed a reduction in cardia coutput (CO) and stroke volume (SV), an augment in systemic vascular resistance (SVR) and left cardiac woke (LCW) of the model group compared with the sham-operated group. Moreover, the scores of tongue and pulse manifestation were also significantly increased in the model group with abnormal color of tongue (P < 0.05, 0.01). Compared with the model group, Shengmai Capsules and Tongmai Yangxin Pills reduced the area of myocardial ischemia and infarction, increased the values of CO and SV, decreased the scores of tongue and pulse manifestation and improved tongue color (P < 0.05, 0.01). In addition, Tongmai Yangxin Pills also reduced SVR (P<0.01). Conclusion: The syndrome of deficiency of both qi and yin in mini pigs could be partly manifested in later stage of myocardial ischemia reperfusion injury. Tongmai Yangxin Pills can improve tongue and pulse signs, protect myocardial tissue, and recover abnormal hemodynamics, which can establish foundation for the further clinical application.
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The comparison on evaluating blood stasis syndrome in sleep deprived rats was carried out by using R, G, B image analysis of Tongue and palm as well as auricle, palm surface laser Doppler flow perfusion. The experiment was performed by means of a small platform on the water environment for sleep deprivation. The rats were weekly weighed at fixed time, and their macroscopic signs were observed; and their tongue and palm images of the control and model group were respectively collected by the SLR camera at the 2nd, 4th and 6th week. Then the color saturation analysis was performed by means of proofreading with the standard colorimetric card. At the same time, the laser dopper flowmetry was used to analyze the perfusion of auricle and foot flow in rats. It turned out that there was no significant difference in the R,G,B value of the tongue and palm in rats between normal group and model group at the first stage(at the 2nd week), so were the perfusion of auricle and foot flow in rats. But at the second stage (at the 4th week), the R value of tongue in model group rats was obviously lower than that in normal group(<0.01), and the other value (G,B) of tongue in module rats had a decease tendency, but there was no statistical significance. However, the perfusion of left and right auricle flow in model group rats were dramatically decreased as compared with the normal group(<0.01); there was still no significant difference in the perfusion of the palm between two groups. It was found that R,G,B value in model group had a lower trend as compared with the control group of the tongue and palm images at the third stage (at the 6th week), but no statistically significant difference. The perfusion of left and right auricle flow in model group was constantly decreased as compared with the normal group(<0.01).Right and left foot blood flow was lower than the normal group, but no statistically significant difference. We can safely conclude that the results of the R, G, B values of the tongue in rats could objectively reflect the characteristics of the rats with blood stasis syndrome, which were consistent with the diagnosis of clinical tongue image. As a method of microcirculation evaluation, the surface laser doppler perfusion of auricle can exhibit the characteristics of blood stasis in model rats, but also was more objective and reproducible. Therefore, the combination of R, G, B value of tongue as well as auricle laser doppler blood flow is more beneficial to the objective evaluation of index in the later study of traditional Chinese medicine blood stasis syndrome model.
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Blood stasis syndrome is the pre-state of thrombotic disease. The model of blood stasis syndrome in rats was induced by sleep deprivation to study on effects of blood stasis syndrome on platelet activation. The weight, the color of tongue and hemorheology for the blood stasis syndrome of Chinese medicine were measured after modeling. The release of platelet granules and platelet activation factors in plasma were detected by ELISA kit related indicators to provide experimental basis for platelet function evaluation and related drug effects in syndrome research. The results showed that the weight of the model group rats was significantly lower than that of the normal group (<0.01). The tongue showed a dark purple blood stasis pattern, and the R, G and B values of the tongue surface in model group were significantly lower than those of the normal group (<0.01). The hemorheological parameters including high shear, middle shear and low shear viscosity in whole blood were significantly higher than those in the normal group (<0.01). But plasma viscosity did not change significantly. The release levels of platelet α particles (GMP-140, -TG, PF4) and dense particles (ADP, 5-HT) were significantly higher than those in the normal group (<0.01). The levels of TXB₂ and 6-keto-PGF₁α in plasma were significantly higher than those in the normal group (<0.01). The ratios of TXB₂ and 6-keto-PGF₂α were also significantly higher than those in the normal group (<0.01). The levels of PAF in plasma in model group were significantly higher than those in the normal group (<0.01). It was concluded that platelet functions could be changed induced by sleep deprivationin rats with blood stasis syndrome, and there might be inflammation and endothelial cell dysfunction.
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This study was designed to investigate the effect of Yinxing Mihuan oral solution on rats with myocardial ischemia injury. Left anterior descending (LAD) coronary artery was occluded in rats to establish the model. Yinxing Mihuan oral solution was given by intragastric administration daily for one week at dosage of 309 and 618 mg·kg-1. Cardiac ultrasound function, pathologic change and serum myocardial enzymes were determined to evaluate the effect of Yinxing Mihuan oral solution. The heart function was significantly reduced in the model group compared with sham operation group, and the pathologic damage was clear. The changes were significantly improved by Diltiazem hydrochloride tablets in heart function and ejection fraction (P -1) (P P < 0.01). In addition, Yinxing Mihuan oral solution decreased the myocardial damage and inhibited inflammatory reaction, and inhibited platelet activation factor. Yinxing Mihuan oral solution can protect against myocardial ischemia injury, inflammation and platelet activation in the rat model.
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This study was conducted to investigate the effects of Danlou (correspondence between prescription and syndrome) tablet and Shengmai capsule (non-correspondence between prescription and syndrome) on mini-swine phlegm-stasis syndrome of coronary heart disease (CHD). 24 mini-swines were randomly divided into normal control group, model group, Danlou tablet group (0.24 g·kg-1) and Shengmai capsule group (0.14 g·kg-1). Phlegm-stasis syndrome of coronary heart disease was established by high-fat feeding and coronary intervention balloon injury. After 8 weeks of administration, blood lipid levels and blood rheology was detected. Echocardiography was used to examine the changes in heart function, and the extent of infarction was determined by nitro blue tetrazolium (NBT) staining method. The main symptoms, accompanied symptoms, tongue and pulse signs of the coronary heart disease mini-swine with phlegm-stasis syndrome were observed according to the symptom-graded scoring method. The results showed that Danlou tablet decreased serum total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) (P P P P P P P P P P P P < 0.05). However, Shengmai capsule failed to show therapeutic effects on blood lipid metabolism, the myocardial infarction area and primary symptom and syndrome score. The results suggest that as a drug for the treatment of Qi and Yin deficiency syndrome of CHD, Danlou tablet has limited therapeutic effects on phlegm-stasis syndrome of CHD. Only by the prescription correspondence with syndrome, using drug for the treatment of phlegm-stasis syndrome of CHD to treat phlegm-stasis syndrome of CHD, the prescription has a comprehensive therapeutic effect.
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Coronary microvascular dysfunction (CMD) is a common mechanism for some heart disease like cardiac X syndrome and no-reflow phenomenon after percutaneous coronary intervention(PCI). With the development of medical imageology, CMD has received increased attention. Animal model of CMD is indispensable tool for the research of pathogenesis and treatment evaluation, therefor choose an appropriate animal model is the first issue to carry out CMD research. Experimental and clinical studies have shown unique effectiveness of traditional Chinese medicine(TCM) in CMD therapy. Clarifying of the TCM therapeutic effect mechanisms and seeking an optimal solution of combination of traditional Chinese and western medicine will be the focus of future research. This paper reviewed the establishment and evaluation of CMD animal model, as well as the intervention study of TCM on CMD. The article aims to provide reference for the basic research of CMD and the TCM experimental study on CMD.
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Pericytesis a kind of widespread vascular mural cells embedded within the vascular basement membrane of blood microvessels, constituting the barrier of capillaries and tissue spaces together with endothelial cells. Pericytes communicate with microvascular endothelial cells through cell connections or paracrine signals, playing an important role in important physiological processes such as blood flow, vascular permeability and vascular formation. Pericytes dysfunction may participate in some microvascular dysfunction, and also mediate pathological repair process, therefore pericytes attracted more and more attention. Traditional Chinese medicine suggests that microvascular dysfunction belongs to the collaterals disease; Qi stagnation and blood stasis in collaterals result in function imbalance of internal organs. Traditional Chinese medicine (TCM) has shown effects on pericytes in microvascular dysfunction, for example qi reinforcing blood-circulation activating medicines can reduce the damage of retinal pericytes in diabetic retinopathy. However, there are some limitations of research fields, inaccuracy of research techniques and methods, and lack of mechanism elaboration depth in the study of microvascular lesion pericytes. This paper reviewed the biological characteristics of pericytes and pericytes in microvascular dysfunction, as well as the intervention study of TCM on pericytes. The article aims to provide reference for the research of pericytes in microvascular dysfunction and the TCM study on pericytes.
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To establish Qi-deficiency and blood-stasis syndrome type coronary heart disease models by fatigue running exercise and high ligation of left anterior descending coronary artery (LAD), male Wistar rats were selected and randomly divided into sham operation group (JSS), coronary ligation group (DZ), fatigue running exercise+coronary ligation group (PZ). Coronary ligation alone was done in DZ group; while the rats in PZ group had running exercise in on the animal treadmill system for 2 weeks to establish fatigue models, and then coronary ligation was done based on the models. The exhausted running was maintained for 28 days at the frequency of 1 time/2 days after operation. Twenty-eight to thirty-one days after the operation, all the rats were observed for macroscopic physical signs, and ultrasonic echocardiography indexes and breathing extent of the rats were collected to evaluate the main symptoms of rats with Qi-deficiency and blood-stasis syndrome type coronary heart disease; related indexes of open field test, exhaustive running time, and colorimetric analysis data on images of plantar were collected to evaluate the accompanied symptoms; colorimetric analysis data on lingual surface was collected to evaluate the tongue characteristics; pulse distension data was collected to evaluate the pulse condition, and meanwhile, blood rheology and coagulation function were also detected. From the 28th day postoperatively, the main symptoms, accompanied symptoms, tongue characteristics and pulse conditions of rats in PZ group conformed to the symptoms of coronary heart disease and Qi-deficiency and blood-stasis syndrome. Combined with related pathological results, the study revealed that Qi-deficiency and blood-stasis syndrome type coronary heart disease models could be successfully established by fatigue running exercise and high ligation of left anterior descending coronary artery for the rats.
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Salvianolic acid A (SAA), one of the major active water-soluble salvianolic acids of traditional Chinese medicine Salvia miltiorrhiza Bunge, has been reported to be effective on anti-myocardial ischemia, anti-oxidation and anti-thrombus. This study aimed to investigate appropriate administration route on dogs with acute myocardial ischemia(AMI). Twenty-four dogs were randomized into four groups (n=6), model, oral administration of SAA (8 mg•kg⁻¹), intravenous administration of SAA (4 mg•kg⁻¹), intravenous administration of Herbesser(0.5 mg•kg⁻¹) as positive drug group. AMI model was established by ligating left anterior descending coronary arteries(LAD) of dogs. Changes of ST segment were determined by epicardial electrocardiogram(ECG), coronary blood flow (CBF) and myocardial oxygen consumption were measured by ultrasonic Doppler flow meter, serum creatine kinase (CK) and lactate dehydrogenase (LDH) were observed by fully automatic biochemical analyser. Myocardial infarct size was assessed by nitro blue tetrazolium (NBT) staining. Both oral and intravenous administration of SAA reduced the myocardial infarct area/left ventricle area significantly [(16.73±6.52)% and (13.19±2.38)%, compared with (24.35±4.89)% in model group, P<0.01). Oral administration of SAA improved the ECG performance of Σ-ST from 30-190 min after ischemia (P<0.05-0.01), while intravenous SAA had a rapid onset (10-190 min after ischemia, P<0.05-0.01). Compared with model group, oral and intravenous SAA both decreased serum CK and LDH significantly (P<0.05-0.01), while the difference of intravenous administration is more significant. SAA protects myocardium in canine experimental myocardial infarction models. Intravenous administration of SAA alleviates myocardial infarction with greater significance than oral route.
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The efficacy not only is summarized by clinical effect of Chinese herbal compound on theory of traditional Chinese medicine, but also is manifested to clinical effect by interaction of many intricate chemical substances. The efficacy of Chinese herbal compound is current research focus in field of traditional Chinese medicine. By currently knowing in different aspects which included the progression in efficacy of Chinese herbal compound, symptomatic efficacy of Chinese herbal compound, the relationship between the efficacy and pharmacologic effect of Chinese herbal compound, the efficacy related pharmacodynamic substance and the evaluation of efficacy, it had been summarized mainly problems and methods in research and development process of the efficacy of Chinese herbal compound in this paper. Paper also elucidated problems that need to pay attention in research of efficacy in order to provide references for clinical and experimental studies of efficacy in Chinese herbal compound, boost research and development level of new traditional Chinese drug and facilitate modernization of traditional Chinese medicines.
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To investigate the effects and mechanisms of total flavones of Epimedium (TFE) on oxidative stress induced by myocardial ischemia/reperfusion injury in rats, forty male SD rats were randomly divided into sham operated group, model group, diltiazem group and flavonoids of Epimedium low and high doses groups with 8 rats in each. Myocardial ischemia/reperfusion injury model was induced by ligaturing the left anterior descending artery for 30 min followed reperfusion for 4 h after TFE was taken by intragastric administration for 4 days. The degree of myocardial infarct was observed by N-BT staining. The concentrations of MDA and activities of SOD and T-AOC in cardiac tissue were measured by colorimetry. Serum TnI concentrations were checked by ELISA. HE stain was used to observe myocardium structure under light microscope. Expressions of SIRT1 and Nrf2 in cardiac tissue were evaluated by immunohistochemistry method and Western blot, respectively. Compared with the model group, the degree of myocardial infarct, MDA concentration in cardiac tissue and the levels of TnI in serum significantly decreased in the diltiazem group and flavonoids of Epimedium low and high doses groups (P<0.05 or P<0.01); flavonoids of Epimedium low and high doses groups and the diltiazem group also showed improvements in myocardium structure under ischemia/reperfusion injury. TFE significantly increased the activity of SOD and T-AOC and the expression of SIRT1 and Nrf2 in cardiac tissue when compared with the model group (P<0.05 or P<0.01). Therefore, TFE can increase anti-peroxidant capacity of myocardium tissue by using intrinsically anti-oxidant signaling pathway of SIRT1 and Nrf2, which can inhibit irreversible damage of cardiomyocytes in myocardial ischemia/reperfusion injury and protect normal function of cardiac tissue.
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<p><b>OBJECTIVE</b>To investigate the regulatory effects of Shenfu Injection (SFI, ) on hemodynamic parameters and serum proteins in rats with post-infarction chronic heart failure (CHF).</p><p><b>METHODS</b>Forty-five healthy Wistar rats were randomized into three groups: sham, heart failure (model) and SFI group. The CHF was induced by left coronary artery ligation. Seven days after the surgical operation, animals in the sham group and the model group received saline (6.2 mL/kg/d), while animals in the SFI group received SFI (6.2 mL/kg d) intraperitoneally. Four weeks later, cardiac hemodynamic parameters were measured via the carotid route. The expression of serum proteins was analyzed by two-dimensional electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometer (MALDI-TOF MS).</p><p><b>RESULTS</b>Recording of hemodynamic parameters showed that left ventricular systolic pressure (LVSP), maximum rate of left ventricular pressure (+dp/dtmax) rise, and maximum rate of left ventricular pressure (-dp/dtmax) decrease, while the left ventricular end diastolic pressure (LVEDP) rose in the model group compared to those in the sham group (P <0.05). The results of the MALDI-TOF MS indicated that haptoglobin (HP), pentraxin 3 (PTX3) and alpha-1-antitrypsin were up-regulated, while serum albumin and 40S ribosomal protein were down-regulated in the model group (P <0.05). Compared with the model group, LVSP, +dp/dtmax and -dp/dtmax were higher, while LVEDP was lower in the SFI group (P<0.05). Expression levels of HP and PTX3 were lower than in the model group (P<0.05).</p><p><b>CONCLUSION</b>SFI could improve hemodynamic function and decrease inflammatory reactions in the pathophysiology of CHF. The serum proteins HP and PTX3 could be potential biomarkers for chronic ischemic heart failure, and they could also be the serum protein targets of SFI.</p>
Subject(s)
Animals , Male , Blood Proteins , Metabolism , C-Reactive Protein , Metabolism , Chronic Disease , Drugs, Chinese Herbal , Therapeutic Uses , Electrophoresis, Gel, Two-Dimensional , Haptoglobins , Metabolism , Heart Failure , Blood , Drug Therapy , Heart Function Tests , Hemodynamics , Hydrogen-Ion Concentration , Imaging, Three-Dimensional , Inflammation , Drug Therapy , Myocardial Ischemia , Blood , Drug Therapy , Phytotherapy , Proteome , Metabolism , Rats, Wistar , Serum Amyloid P-Component , Metabolism , Spectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationABSTRACT
Modern and international studies on new traditional Chinese medicines are the main trend of the development of traditional Chinese medicines at present. In Australia, new traditional Chinese medicines refer to complementary medicines, which are mainly registered and launched as listed medicines. The application documents of registered (listed) medicines in Australia mainly cover detailed description of active pharmaceutical ingredients, pharmacological and toxicological studies, dosage form and adverse effects. Each part has detailed specifications and instructions, which helps ensure that applicants could accurately understand the requirements in application for registering (listing) medicines, and provides very important reference to the studies and development of new traditional Chinese medicines in China.
Subject(s)
Australia , Drug Approval , Drug Evaluation , Medicine, Chinese TraditionalABSTRACT
<p><b>OBJECTIVE</b>To evaluate that the effect of formula of removing both phlegm and blood stasis in improving cardiac function of Chinese mini-swine with coronary heart disease of phlegm-stasis cementation syndrome.</p><p><b>METHOD</b>Totally 36 Chinese mini-swine were randomly divided to six groups: the normal control group, the model group, the Danlou tablet group, and Tanyu Tonzhi Fang(TYTZ) groups with doses of 2. 0, 1. 0 and 0. 5 g kg-1, with six in each group. Except for the normal control group, all of other groups were fed with high-fat diet for 2 weeks. Interventional balloons are adopted to injure their left anterior descending artery endothelium. After the operation, they were fed with high-fat diet for 8 weeks to prepare the coronary heart disease model of phlegm-stasis cementation syndrome. After the operation, they were administered with drugs for 8 weeks. The changes in the myocardial ischemia were observed. The changes in the cardiac function and structure were detected by cardiac ultrasound and noninvasive hemodynamic method.</p><p><b>RESULT</b>Compared with the normal control group, the model group showed significant increase in myocardial ischemia and SVR and obvious decrease in CO, SV and LCW in noninvasive hemodynamic parameters (P <0.05 or P <0.01). The ultrasonic cardiogram indicated notable decrease in IVSd, LVPWs, EF and FS, and remarkable increase in LVIDs (P<0. 05 orP<0.01). Compared with the model group, TYTZ could reduce the myocardial ischemia, strengthen cardiac function, and improve the abnormal cardiac structure and function induced by ischemia (P <0. 05 or P <0. 01).</p><p><b>CONCLUSION</b>TYTZ shows a significant effect in improving cardiac function of Chinese mini-swine with coronary heart disease of phlegm-stasis cementation syndrome. The clinical cardiac function detection method could be adopted to correctly evaluate the changes in the post-myocardial ischemia cardiac function, and narrow the gap between clinical application and basic experimental studies.</p>
Subject(s)
Animals , Coronary Circulation , Coronary Disease , Diagnostic Imaging , Metabolism , Therapeutics , Heart , Hemodynamics , Medicine, Chinese Traditional , Methods , Mucus , Metabolism , Swine , Swine, Miniature , UltrasonographyABSTRACT
<p><b>OBJECTIVE</b>To study the protective effect of formula of removing both phlegm and blood stasis (TYTZ) on myocardial tissues of Chinese mini-swine with coronary heart disease of phlegm-stasis cementation syndrome.</p><p><b>METHOD</b>Totally 36 Chinese mini-swine were randomly divided to six groups: the normal control group, the model group, the Danlou tablet group, and TYTZ groups with doses of 2.0, 1.0, 0.5 g x kg(-1), with six in each group. Except for the normal control group, all of other groups were fed with high-fat diet for 2 weeks. Interventional balloons are adopted to injure their left anterior descending artery endothelium. After the operation, they were fed with high-fat diet for 8 weeks to prepare the coronary heart disease model of phlegm-stasis cementation syndrome in Chinese mini-swine. After the operation, they were administered with drugs for 8 weeks. The SOD activity and MDA content of each group were observed at the 0th week (before the experiment), the 2nd week after the high-fat diet (before the operation or drug administration) , the 6th week after the high-fat diet (4 weeks after the drug administration) and the 10th week after the high-fat diet (8 weeks after the drug administration). Meanwhile, the myocardial enzymogram test and the HE staining pathological observation were performed at the end of the experiment. The changes in the myocardial cell ultra-structure were observed under transmission electron microscope.</p><p><b>RESULT</b>Compared with the normal control group, the model group showed significant decrease in serum SOD activity and notable increase in MDA content from the 2nd week to the end of experiment (P < 0.05 and P < 0.01). In the 10th week, the CK, LDH and CK-MB levels in serum also significantly increased in the model group (P < 0.05 and P < 0.01), with obvious structural abnormality in myocardial tissue pathologic morphology and ultra-structure. Compared with the model group, TYTZ groups showed specific increase in serum SOD activity and oblivious decrease in the MDA level (P < 0.05 or P < 0.01). Meanwhile, TYTZ could significantly decrease serum CK and LDH levels in the model group (P < 0.05 or P < 0.01), attenuate the ischemia injury of myocardial tissue, and improve the ultra-structure of cardiomyocytes.</p><p><b>CONCLUSION</b>TYTZ shows an obvious protective effect on the myocardial injury in Chinese mini-swine with coronary heart disease of phlegm-stasis cementation syndrome. Its mechanism is related to the resistance against free radical oxidation injury and the inhibition of the lipid per-oxidation.</p>
Subject(s)
Animals , Female , Humans , Male , Coronary Artery Disease , Genetics , Metabolism , Drugs, Chinese Herbal , Mucus , Metabolism , Myocardium , Metabolism , Protective Agents , Swine , Swine, MiniatureABSTRACT
<p><b>OBJECTIVE</b>To analyze and summarize changes of syndrome-related biological indices in acute lacuna encephalon infarction patients of upper hyperactivity of Gan yang syndrome (UHGYS), thus providing objective evidence for syndrome typing and disease identification.</p><p><b>METHODS</b>Recruited were 50 patients at Department of Encephalopathy, Xiyuan Hospital, China Academy of Chinese Medical Sciences, who were in line with diagnostic criteria of UHGYS as the experimental group in this study. Another 40 healthy volunteers were recruited as the control group from May 2010 to July 2012. Blood routines (including WBC, RBC, Hb, NEUT%, and LY%), hepatic and renal functions tests (including ALT, AST, TBIL, TP, ALB, Cr, and BUN) were performed by automatic whole blood analyzer and colorimetric technique. The levels of fasting blood glucose, HbAlc, blood lipids (including TC, TG, HDL-C, LDL-C, and VLDL-C), and coagulation functions (including AT-III, PT, PTA, INR, TT, APTT, and FBG, reaction time), renin, angiotensin II, hs-CRP, and Hcy were also measured. The thyroid functions (including FT3, FT4, T3, T4, and TSH) were detected by electrochemiluminescence immunoassay. The levels of tumor necrosis factor alpha (TNF-alpha), IL-6 and IL-1 in serum were measured by ELISA and radioimmunoassay respectively.</p><p><b>RESULTS</b>Compared with the control group, RBC, LY%, ALT, TP, ALB, HDL-C, AT-III activities, contents of PTA and FT4 obviously decreased, TBIL, BUN, Glu, HbAlc, TSH, hs-CRP, renin, Ang II, TNF-alpha, IL-1 and IL-6 significantly increased in the experimental group (P < 0.05, P < 0.01).</p><p><b>CONCLUSION</b>The pathological process of acute lacuna encephalon infarction patients of UHGYS was closely correlated with thyroid functions, the renin-angiotensin-aldosterone system, the extrinsic and intrinsic coagulation systems, as well as inflammation reaction.</p>