1.Effect of Xinkang Tablets on Myocardial Apoptosis Index, Collagen Volume Fraction and Sarcoplasmic Reticulum Ca2+-ATPase Activity of Rats with Adriamycin-induced Heart Failure
Hongxue LYU ; Ting WANG ; Xiaohan YE ; Jinbo WU ; Zhiyuan SU
Journal of Guangzhou University of Traditional Chinese Medicine 2017;34(2):221-226
Objective To explore the effect of Xinkang Tablets on myocardial apoptosis index,collagen volume fraction and sarcoplasmic reticulum Ca2+-ATPase activity of rats with adriamycin-induced heart failure.Methods The chronic heart failure (CHF) SD rat model was established by intraperitoneal injection of doxorubicin.After successful modeling,the rats with CHF were randomly divided into 5 groups,namely model group,western medicine group,and low-,middle-and high-dose of Chinese medicine groups,10 rats in each group.The rats in the above groups were given intragastric administration of distilled water,22.5 μg/kg of Digoxin mixed suspension,9,18,36 g/kg of XinkangTablets,respectively,in the volume of 10 mL/kg of distilled water dilution,once a day,for 5 continuous weeks.Another the same batch of 10 SD rats were randomly allocated to the sham operation group,and were treated with intragastric administration of the same volume of distilled water.And then the apoptotic rate of myocardial cells was measured by TUNEL method,the collagen volume fraction (CVF) was measured after Masson staining,and the sarcoplasmic reticulum Ca2+-ATPase activity was determined by inorganic phosphate assay.Results Compared with the sham operation group,the apoptotic rate of myocardial cells and CVF in the model group were increased(P < 0.01),indicating that the myocardial remodeling occurred in rats with CHF.Compared with the model Group,the apoptotic rate of western medicine group and three Chinese medicine groups was significantly decreased(P < 0.01),suggesting that Digoxin and Xinkang Tablets can relieve apoptosis to certain extent.The CVF in Digoxin group and middle-and high-dose of Chinese medicine groups were lower than those in the model Group (P< 0.05 or P< 0.01),indicating that Digoxin and Xinkang Tablets can delay the myocardial fibrosis.Last but not least,the SERCA2a activities in the middle-and high-dose of Chinese medicine groups were higher than those in the model group (P < 0.05 or P < 0.01),suggesting that Xinkang Tablets may relieve myocardial remodeling and improve cardiac function through the regulation of SERCA2a activity.Conclusion Xinkang Tablets decrease the apoptotic rate and myocardial cell volume fraction probably through the regulation of SERCA2a activity,which may play a role in counteracting apoptosis and myocardial fibrosis,and ultimately delay the remodeling of the myocardium.
2.Clinical observation on treating resistant hypertension with modifiedHuanglian-Jiedu decoction
Wen LI ; Yingjun CHEN ; Xiaohan YE ; Hongxue LYU ; Feiyuan LI ; Ting WANG ; Chijun HOU
International Journal of Traditional Chinese Medicine 2015;(7):598-601
Objective To evaluate the therapeutic effect of modifiedHuanglian-Jiedudecoction for resistant hypertension and explore its possible mechanism.Methods A total of 90 patients with resistant hypertension were recruited and randomly divided into a treatment group and a control group, 45 patients in each group. The control group was treated with oral administration of irbesartan and hydrochlorothiazide tablets and controlled-release nifedipine tablets, while the treatment group was further added modifiedHuanglian-Jiedu decoction for 4 weeks. Plasma endothelin (ET) and calcitonin gene-related peptide (CGRP) were measured by radioimmunoassay.Rusults The total efficiency according to the TCM syndrome in the treatment group was 86.7%(39/45) which was higher than 64.4%(29/45) in the control group(χ2=4.873,P=0.027). The systolic blood pressure (SBP) and diastolic blood pressure (DBP) decreased after the treatment in both groups ( SBP in the treatment group: 119.26 ± 9.34 mmHgvs.172.11 ± 10.52 mmHg,t=25.201,P<0.01; DBP in the treatment group: 78.18 ± 7.21 mmHgvs.111.12 ± 11.16 mmHg,t=16.631, P<0.01; SBP in the control group: 145.21 ± 7.56 mmHgvs.171.32 ± 11.15 mmHg,t=13.002,P<0.01; DBP in the control group: 93.57±8.13 mmHgvs. 109.89 ± 12.21 mmHg,t=7.463,P<0.01), while the decrease of SBP (t=14.487,P<0.01) and DBP (t=9.501, P<0.01) in the treatment group was more greater than those in the control group. The control rate of blood pressure in the treatment and control groups were 73.3% (33/45) and 55.6% (25/45), respectively, there had no significant difference (χ2=2.376,P=0.123). The plasma ET in the treatment group was significantly decreased than that in the control group (75.68 ± 10.67 ng/Lvs.112.79 ± 12.26ng/L;t=15.317,P<0.05), and CGRP significantly increased (49.87 ± 4.75 ng/Lvs.33.87 ± 7.89 ng/L;t=11.654,P<0.05).Conclusion Modified Huanglian-Jiedudecoction may have some therapeutic effect for resistant hypertension, its mechanism may be involved in ET decreasing and CGRP increasing.
3.Mechanism of Xinkang Prescription for Purging the Lung and Promoting Diuresis in Treating Heart Failure by Improving Phosphorylation of Phospholamban
Yubing ZHANG ; Lingjun WANG ; Ting WANG ; Puli XU ; Luyi TANG ; Hongxue LYU
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(10):1512-1519
Objective To explore the mechanism of Xinkang Prescription (Descurainiae Semen Lepidii Semen,Armeniacae Semen Amarum,Poria,Astragali Radix,Citri Reticulatae Pericarpium,Sparanii Rhizoma) for purging the lung and promoting diuresis in treating heart failure by regulating phosphorylation of phospholamban (PLN). Methods Forty-eight C57BL/6J mice were randomly divided into sham-operation group,model group,low-,medium-and high-dose Xinkang Prescription groups(0.455,0.91,1.82 g·kg-1),as well as Entresto group (25 mg·kg-1),with eight mice in each group. The model of ischemic heart failure was established by ligating the left anterior descending coronary artery in mice. After the model was successfully replicated,mice were orally administered with the above-mentioned dosages of Xinkang Prescription and Entresto once a day for four weeks,while sham-operation group and model group were given 0.9% sodium chloride solution by gavage at the same time. Echocardiography was used to detect the cardiac function of the mice in each group,including left ventricular ejection fraction (LVEF),left ventricular fractional shortening (LVFS),left ventricular end-diastolic dimension (LVEDD) and left ventricular end systolic diameter (LVESD). Hematoxylin-eosin (HE) staining was used to observe the pathological changes in cardiac tissue of mice. qRT-PCR was used to detect the mRNA expression of BNP. Western Blot and Jess were used to detect the expression of PLN,p-Thr17-PLN,p-Ser16-PLN,sarcoplasmic reticulum calcium ATPase 2a (SERCA2a),protein kinase A (PKA),p-PKA,Ca2+/calmodulin-dependent kinaseⅡ(CaMKⅡ) and p-CaMKⅡ in cardiac tissue,and to calculate the ratio of SERCA2a/PLN. The SERCA2a activity was determined by the inorganic phosphorus method.Results Compared with the sham-operation group,the model group showed a significant decrease in LVEF and LVFS(P<0.01) and a significant increase in LVEDD and LVESD (P<0.01). HE staining showed the fibril of cardiac muscle broke and disarranged,accompanied by inflammatory cell infiltration. The mRNA expression of BNP was significantly up-regulated (P<0.01),and the protein expressions of p-Ser16-PLN,p-Thr17-PLN,p-PKA,the ratio of SERCA2a/PLN and SERCA2a activity were significantly down-regulated (P<0.01),while the expression of p-CaMKⅡ was up-regulated (P<0.01). Compared with the model group,LVEF and LVFS in medium-,high-dose Xinkang Prescription groups were significantly increased(P<0.01),while LVEDD and LVESD were significantly decreased (P<0.01). HE staining showed significant improvement in the pathological damage of cardiac tissue. The expression level of BNP was significantly decreased (P<0.01),while the protein expressions of p-Ser16-PLN,p-Thr17-PLN,p-PKA,the ratio of SERCA2a/PLN and SERCA2a activity were significantly increased (P<0.01). The protein expression of p-CaMKⅡ was remarkably decreased(P<0.05). Conclusion Xinkang Prescription can effectively improve cardiac function of mice with heart failure,which may be related to enhance phosphorylation levels of phospholamban.