1.Effects of Xuefu Zhuyu Granule and Danlou Tablet on Anti-atherosclerosis Rats and Potential Mechanisms.
Jing MIAO ; Xin-bin ZHOU ; Wei MAO ; Jie CHEN ; Xiao-ming XU
Chinese Journal of Integrated Traditional and Western Medicine 2016;36(1):80-84
OBJECTIVETo observe anti-atherosclerotic effect of Xuefu Zhuyu Granule (XZU) and Danlou Tablet (DT) on blood lipids, platelet derived growth factor (PDGF), vascular smooth muscle cells (VSMCs) proliferation, extracellular signal-regulated kinase (ERK) signal pathway in atherosclerosis (AS) model rats, and to explore their potential mechanisms.
METHODSForty male Wistar rats were randomly divided into five groups, i.e., the normal control group, the model group, the Atorvastatin group, the DT group, the XZG group, 8 in each group. Rats in the normal control group were fed with basic forage for 12 weeks, while rats in the other four groups were fed with high fat forage plus intraperitoneal injection of vitamin D3 to build AS model. Then rats in the model control group, the Atorvastatin group, the DT group, the XZG group were administered with normal saline, Atorvastatin suspension (0.18 mg/mL), DT suspension (45 mg/mL), and XZG (1 g/mL) by gastrogavage for 8 successive weeks, respectively. After intervention serum levels of TC, TG, LDL-C, HDL-C, and PDGF were detected by ELISA. Pathological changes in thoracic aorta were observed by HE staining. Protein expression levels of ERK1/2 and pERK1/2 in thoracic aorta were measured by Western blot.
RESULTSCompared with the normal group, serum TC, TG, LDL-C, PDGF levels, and expression levels of ERK1/2 and pERK1/2 significantly increased (P <0. 05) in the model control group. HE staining showed irregular intimal thickness, accumulated endothelial foam cells, lipids deposited, disarranged media VSMCs, forming typical AS plaque. Compared with the model group, TC and PDGF levels decreased in all medicated groups (P < 0.05, P < 0.01). Serum levels of TG and LDL-C significantly decreased in the Atorvastatin group and the DT group (P < 0.01, P < 0.05). Expressions of ERK1/2 and pERK1/2 significantly decreased in the Atorvastatin group, the DT group, and the XZG group (P < 0.01). HE staining also showed typical AS plaque in three medicated groups, but with reduced pathological degree of endometrial hyperplasia and plaque area.
CONCLUSIONSXZG and DT could reduce the plaque area and attenuate pathological degree of AS in model rats, thereby postponing the progress of AS. Its mechanism might be achieved through reducing serum lipids and release of PDGF, inhibiting ERK signal pathway activation and VSMC proliferation.
Animals ; Aorta, Thoracic ; Atherosclerosis ; drug therapy ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; therapeutic use ; Extracellular Signal-Regulated MAP Kinases ; Lipids ; Male ; Plaque, Atherosclerotic ; Rats ; Rats, Wistar ; Tablets
2.Danlou Tablet Fought against Inflammatory Reaction in Atherosclerosis Rats with Intermingled Phlegm and Blood Stasis Syndrome and Its Mechanism Study.
Jie CHEN ; Hong-wen CAI ; Jing MIAO ; Xiao-ming XU ; Wei MAO
Chinese Journal of Integrated Traditional and Western Medicine 2016;36(6):703-708
OBJECTIVETo observe the effects of Danlou Tablet (DT) on inflammatory reaction, and expressions of lipoprotein-associated phospholipase A2 (LP-PLA2), secretory phospholipase A2 (sPLA2), and to analyze potential mechanisms.
METHODSForty male Wistar rats were randomly and equally divided into five groups, i.e., the normal control group, the model group, the Western medicine (WM) group, the low dose DT group, the high dose DT group, 8 in each group. Rats in the normal control group were fed with basic forage for 12 successive weeks, while AS rat model was established in rats of the other four groups by feeding high fat and sugar forage plus intraperitoneal injection of vitamin D₃. Normal saline, atorvastatin calcium suspension (at the daily dose of 1.8 mg/kg), low dose DT suspension (at the daily dose of 450 mg/kg), and high dose DT suspension (at the daily dose of 900 mg/kg) were administered to rats in the model group, the WM group, the low dose DT group, the high dose DT group respectively by gastragavage for 8 successive weeks. The general condition of all rats was observed. Rats were sacrificed after gastric administration and their serum collected. Serum levels of lipids (TC, TG, HDL-C, LDL-C) and inflammatory factors [IL-6, TNF-α, monocyte chemoattractant protein 1 (MCP-1), oxidized low-density lipoprotein (ox-LDL), lipoprotein-associated phospholipase A2 (LP-PLA2), secretory phospholipase A2 (sPLA2)] were detected. Pathological changes of thoracic aorta were observed by HE staining. Protein and gene expressions of LP-PLA2 and sPLA2 in thoracic aorta were measured by Western blot and real-time fluorescent quantitative PCR respectively.
RESULTSCompared with the normal control group, rats in the model group were in low spirits and responded poorly. Typical atherosclerotic plaque could be seen in thoracic aorta of rats in the model group. Serum levels of TC, TG, LDL-C, IL-6, TNF-α, MCP-1, ox-LDL, LP-PLA2, and sPLA2 significantly increased (P < 0.05); protein and gene expressions of LP-PLA2 and sPLA2 in rat thoracic aorta increased (P < 0.05) in the model group. After 8 weeks of intervention, rats in 3 medication groups appeared active, and HE staining showed subsidence of plaque in rat thoracic aorta. Compared with the model group, serum levels of TC, TG, LDL-C, IL-6, TNF-α, MCP-1, ox-LDL, and LP-PLA2 decreased in 3 medication groups (P < 0.01, P < 0.05); serum sPLA2 level decreased, protein and mRNA expressions of LP-PLA2 and sPLA2 in rat thoracic aorta decreased in the WM group (P < 0.01, P < 0.05); protein and mRNA expressions of LP-PLA2 in rat thoracic aorta significantly decreased in the low dose DT group (P < 0.01, P < 0.05), and those of LP-PLA2 and sPLA2 decreased in the high dose DT group (P < 0.01, P < 0.05).
CONCLUSIONDT could fight against inflammatory reaction and AS possibly through inhibiting LP-PLA2 expression and reducing ox-LDL production.
1-Alkyl-2-acetylglycerophosphocholine Esterase ; blood ; Animals ; Aorta, Thoracic ; pathology ; Atherosclerosis ; drug therapy ; Chemokine CCL2 ; blood ; Drugs, Chinese Herbal ; pharmacology ; Inflammation ; drug therapy ; Interleukin-6 ; blood ; Lipids ; blood ; Lipoproteins, LDL ; blood ; Male ; Phospholipases A2 ; blood ; Plaque, Atherosclerotic ; Random Allocation ; Rats ; Rats, Wistar ; Tablets ; Tumor Necrosis Factor-alpha ; blood
4.Effect of homocysteine on plaque formation and oxidative stress in patients with acute coronary syndromes.
Guang WANG ; Jie-Ming MAO ; Xian WANG ; Fu-Chun ZHANG
Chinese Medical Journal 2004;117(11):1650-1654
BACKGROUNDCardiovascular diseases, especially coronary artery disease (CAD), are major causes of death in industrialized countries. Elevated concentrations of plasma homocysteine (Hcy) have been associated with an increased risk of CAD. Increased plasma levels of chemokine, characterized by their ability to induce migration and activation of leukocytes, may contribute to the pathogenesis of CAD. This study was designed to investigate the changes of plasma Hcy, monocyte chemoattractant protein-1 (MCP-1) and oxidative stress markers in acute coronary syndrome patients.
METHODSA total of 149 subjects were divided into four groups: 50 patients with unstable angina, 30 patients with acute myocardial infarction, 20 coronary restenosis patients after percutaneous coronary intervention and 49 healthy control subjects. Plasma levels of Hcy, MCP-1, malondialdehyde and superoxide dismutase were measured.
RESULTSPlasma levels of Hcy and MCP-1 showed significant increases in unstable angina, acute myocardial infarction and restenosis patients compared with control subjects (P < 0.05, respectively). Plasma levels of malondialdehyde were significantly increased in unstable angina and acute myocardial infarction patients when compared with control subjects (P < 0.05, respectively). Plasma superoxide dismutase levels were significantly reduced in acute myocardial infarction patients when compared with control group (P < 0.01).
CONCLUSIONHcy might act as an atherogenic factor through promoting chemokine, reactive oxygen species and oxidized low density lipoprotein production and thereby convert a stable plaque into an unstable potentially occlusive lesion.
Acute Disease ; Adult ; Aged ; Chemokine CCL2 ; blood ; Coronary Artery Disease ; etiology ; Coronary Disease ; blood ; complications ; metabolism ; Female ; Homocysteine ; blood ; Humans ; Lipoproteins, LDL ; metabolism ; Male ; Malondialdehyde ; blood ; Middle Aged ; Oxidative Stress ; Superoxide Dismutase ; blood
5.Folic acid attenuates homocysteine induced human monocytes chemokine secretion via reducing NADPH oxidase activity.
Ying WANG ; Guang WANG ; Fu-chun ZHANG ; Jie-ming MAO ; Jing DAI
Chinese Journal of Cardiology 2007;35(10):956-959
OBJECTIVETo investigate the effect of folic acid on homocysteine (Hcy)-induced chemokine secretion and NADPH oxidase activity in human monocytes.
METHODSHuman monocytes from healthy volunteers were incubated with Hcy (100 micromol/L) with or without folic acid (5 micromol/L) for 24 h; MCP-1 and IL-8 were assessed by ELISA. DCFH-DA was added to monitor intracellular ROS production on confocal microscopy. A cytochrome c reduction assay was used to measure NADPH oxidase activity.
RESULTSThe Hcy-induced secretion of MCP-1 and IL-8 was significantly reduced by folic acid [(1.88 +/- 0.51) ng/ml vs. (4.36 +/- 0.72) ng/ml vs. (2.40 +/- 0.60) ng/ml and (4.9 +/- 1.9) ng/ml vs. (12.7 +/- 1.5) ng/ml vs. (7.2 +/- 1.9) ng/ml, all P < 0.05]. The Hcy-induced production of ROS was also significantly attenuated by folic acid. Moreover, the Hcy-induced NADPH oxidase activity increase was significantly inhibited by cotreatment with folic acid.
CONCLUSIONFolic acid may attenuate oxidative stress induced by Hcy by reducing NADPH oxidase activity in monocytes.
Cells, Cultured ; Chemokines ; secretion ; Folic Acid ; pharmacology ; Homocysteine ; pharmacology ; Humans ; Interleukin-8 ; metabolism ; Monocytes ; drug effects ; secretion ; NADPH Oxidases ; metabolism ; Oxidative Stress ; drug effects ; Receptors, CCR2 ; metabolism
6.Calcitonin gene-related peptide gene therapy suppresses reactive oxygen species in the pancreas and prevents mice from autoimmune diabetes.
Fei SHE ; Wei SUN ; Jie-Ming MAO ; Xian WANG
Acta Physiologica Sinica 2003;55(6):625-632
Reactive oxygen species (ROS) is involved in autoimmune destruction of islet beta cells, which has been proven to be an important underlying pathogenesis for insulin dependent diabetes mellitus (IDDM). Calcitonin gene-related peptide (CGRP) is a widely distributed neuropeptide, which has been found to play an important role in protecting myocytes from ROS. We hypothesized that exogenous CGRP gene administration before the pathogenic stage of insulitis might suppress the production of ROS and provide a hopeful therapeutic intervention for autoimmune diabetes. We performed CGRP gene transfer by injecting naked plasmid directly into skeletal muscles of mice with electroporation enhancement to achieve a continuous expression of CGRP in skeletal muscles, and thereby its secretion into the circulation. The effect of CGRP gene transfer on the pathogenesis of diabetes was studied in autoimmune diabetic mice induced by multiple low dose streptozotocin (MLDS). The CGRP gene therapy decreased morbidity of autoimmune diabetes, and significantly ameliorated hyperglycemia in these mice. CGRP gene transfer inhibited the production of ROS and malondialdehyde (MDA). In addition, it enhanced the activity of catalase (CAT) and superoxide dismutase (SOD) significantly. The data suggest that intramuscular CGRP gene transfer ameliorates autoimmune destruction of islet beta cells, resulting in significant reduction in diabetes incidence of MLDS diabetes mice. CGRP benefits might be mediated at least in part by inhibiting the oxidative stress in islet beta cells of these mice.
Animals
;
Calcitonin Gene-Related Peptide
;
administration & dosage
;
genetics
;
therapeutic use
;
Diabetes Mellitus, Experimental
;
prevention & control
;
Diabetes Mellitus, Type 1
;
prevention & control
;
Gene Transfer Techniques
;
Genetic Therapy
;
Injections, Intramuscular
;
Islets of Langerhans
;
metabolism
;
Male
;
Mice
;
Mice, Inbred C57BL
;
Mice, Transgenic
;
Pancreas
;
metabolism
;
Reactive Oxygen Species
;
metabolism
;
Superoxide Dismutase
;
metabolism
;
Transgenes
;
genetics
7.Assisted semen collection using two phosphodiesterase type 5 inhibitors (Tadalafil and Sildenafil) in infertile men with mild erectile dysfunction.
Wen-hao TANG ; De-feng LIU ; Hui JIANG ; Lu-lin MA ; Kai HONG ; Lian-ming ZHAO ; Jia-ming MAO ; Yi YANG ; Ju ZHANG ; Ling GAO ; Xin-jie ZHUANG ; Jie QIAO
Chinese Medical Journal 2013;126(14):2788-2789
8.Surgical treatment for degenerative lumbar scoliosis associated with spinal stenosis.
Zhao-guang MAO ; Qing-xin WU ; Jie-ming ZHU ; Chun-de LI ; Tian-yue ZHU
China Journal of Orthopaedics and Traumatology 2008;21(11):860-862
OBJECTIVETo study surgical techniques for degenerative lumbar scoliosis associated with lumbar stenosis and evaluate their clinical significane.
METHODSThirty-two patients with degenerative lumbar scoliosis associated with spinal stenosis were treated by techniques of posterior lumbar interbody fusion or posterolateral fusion and pedicle screws. There were 18 male and 14 female with 56.8 years old on the average (ranging from 49 to 75 years). There were no evident change of lumberlordosis in 15 cases, and lumber lordosis were obvious loss associated with lumbar subluxation in 17 cases. The correcting, the improvement of back and leg pain, complications and followed-up results were analyzed retrospectively.
RESULTSThirty-two cases were followed-up for 6 to 39 months (the average time of 13 months). The average correction rate of scoliosis was 58.0% and the rate of pain relief was (80.2 +/- 5.8)%. There were two cases of dura sac laceration, two cases of nerve roots injury and a case of pseudoarthritis. During followed-up, correction rate and height of disc spaces were not lost. Shift of interbody cages were no displaced; all the internal fixation got well fusion and the rate of fusion for the bone graft was 96.9%.
CONCLUSIONPosterior pedicle screws combined with interbody fusion or posterolateral fusion is a safe and effective surgical treatment for degenerative lumbar scoliosis associated with lumbar stenosis.
Aged ; Bone Screws ; Female ; Fracture Fixation, Internal ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Scoliosis ; surgery ; Spinal Fusion ; Spinal Stenosis ; complications ; surgery ; Treatment Outcome
9.Synergistic proliferation induced by insulin and glycated serum albumin in rat vascular smooth muscle cells.
Rong HE ; Ai-Juan QU ; Jie-Ming MAO ; Xian WANG ; Wei SUN
Acta Physiologica Sinica 2007;59(1):1-7
Hyperglycemia, advanced glycation end products (AGEs), hyperinsulinemia and dyslipidemia may play roles in the development of diabetes-associated atherosclerosis and post-angioplasty restenosis. Clinically, their effects seem to be synergic. However, few studies have focused on the synergistic action of these factors. In the present study, we investigated whether glycated serum albumin (GSA) has a synergistic effect with insulin on the proliferation of vascular smooth muscle cells (VSMCs). VSMCs were isolated from rat thoracic aortas and cultured in fetal bovine serum (FBS)-free medium for 24 h, then exposed to GSA, insulin or GSA + insulin for 48 h with or without pretreatment of mitogen-activated protein kinase (MAPK) inhibitors or the antioxidant N-acetylcysteine (NAC). Cell growth rate was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay or cell counting. The changes of phosphorylated-p38 MAPK and phosphorylated-C-Jun N-terminal kinase 1/2 (JNK1/2) were measured by Western blot analysis. The results showed that only p38 MAPK, but not JNK was activated by GSA and insulin co-incubation. VSMC proliferation was increased by insulin (10-1000 nmol/L) or GSA (10, 100 microg/mL). Co-incubation of insulin (100 nmol/L) and GSA (100 mug/mL) caused a more potent increase in VSMC proliferation than insulin or GSA incubation alone. p38 MAPK inhibitor, SB203580, as well as NAC, could inhibit the VSMC proliferation induced by co-incubation of GSA and insulin. The results show that insulin enhances GSA-induced VSMC proliferation, which may be mediated through a reactive oxygen species (ROS)-p38 MAPK pathway. The synergism of AGEs and insulin may play a detrimental role in the pathogenesis of diabetic atherosclerosis and post-angioplasty restenosis.
Animals
;
Aorta, Thoracic
;
cytology
;
Cell Proliferation
;
drug effects
;
Cells, Cultured
;
Drug Synergism
;
Insulin
;
pharmacology
;
physiology
;
Male
;
Muscle, Smooth, Vascular
;
cytology
;
Myocytes, Smooth Muscle
;
cytology
;
drug effects
;
Phosphorylation
;
Rats
;
Rats, Sprague-Dawley
;
Serum Albumin
;
pharmacology
;
physiology
;
p38 Mitogen-Activated Protein Kinases
;
metabolism