OBJECTIVE: To observe the effects of histones on lung injury and von Willebrand factor (vWF) and fibrinogen (FIB) levels in mice, and to explore the protective effect of heparin. METHODS: Twenty-four male C57BL/6 mice aged 6-10 weeks were divided into control group, histone group and histone+heparin group according to random number table method with 8 mice in each group. The mice in the histone group were injected with histone (50 mg/kg) via the tail vein, and the mice in the histone+heparin group were injected with unfractionated heparin (400 U/kg) via the tail vein at 1 hour after administration of histone, and those in the control group were given the same amount of normal saline. Four hours after histone injection, the lungs of the mice were harvested and the lung wet/dry weight ratio (W/D) and the pulmonary water contents were measured. The pathological changes in lung tissue were observed by hematoxylin and eosin (HE) staining under microscope, and the extent of lung injury was evaluated. The positive expression of vWF which was the marker of endothelial cell injury was observed by immunohistochemistry. The real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the expression level of FIB mRNA in lung tissue. RESULTS: The lung W/D ratio and pulmonary water contents in the histone group were significantly higher than those in the control group [lung W/D ratio: 6.19±0.53 vs. 4.54±0.25, pulmonary water contents: (82.59±2.03)% vs. (78.52±1.51)%, both P < 0.01]. The lung W/D ratio and pulmonary water contents in the histone+heparin group were significantly lower than those in the histone group [lung W/D ratio: 4.84±0.35 vs. 6.19±0.53, pulmonary water contents: (79.21±1.48)% vs. (82.59±2.03)%, both P < 0.01], indicating that the heparin could reduce histone-induced pulmonary edema. Histological examination showed that the alveolar structure of the control group was intact, and the alveolar cavity was clean without exudation. In the histone group, the lungs were significantly damaged. The alveolar wall was thickened, infiltrated by inflammatory cells and focally alveolar hemorrhage, edema, associated with alveolar fibrin deposition and micro-thrombus formation. The lung histopathological score in the histone group was significantly higher than that in the control group (5.15±0.87 vs. 0.18±0.17, P < 0.01). All of the pathological changes were significantly alleviated in the histone+heparin group, and the histopathological score of the lung was significantly lower than that in the histone group (2.28±0.72 vs. 5.15±0.87, P < 0.01), indicating that the histone-induced lung injury was improved by heparin. Immunohistochemistry showed that high vWF expressions of lung tissue were observed in the histone group while there was almost no positive expression in the control group, and the vWF expression in the histone+heparin group was significantly reduced, indicating that heparin protected mice against histone-induced endothelial cell injury. The FIB mRNA expression of lung tissue in the histone group was about 49.82 times of the control group (2^-ΔΔCT: 55.30±18.84 vs. 1.11±0.45, P < 0.01), and the expression of FIB mRNA in the histone+heparin group was decreased, which was 23.87 times of the control group (2^-ΔΔCT: 26.50±9.97 vs. 1.11±0.45, P < 0.01), but it was significantly lower than that in the histone group (2^-ΔΔCT: 26.50±9.97 vs. 55.30±18.84, P < 0.01), indicating that heparin could inhibit histone-induced hypercoagulable environment in lung. CONCLUSIONS Histone causes pulmonary edema, endothelial cell injury and coagulation activation. Heparin could effectively attenuate histone-induced lung injury and coagulation activation.
Animals ; Fibrinogen/metabolism* ; Fibrinolytic Agents/therapeutic use* ; Heparin/therapeutic use* ; Histones ; Lung/metabolism* ; Male ; Mice ; Mice, Inbred C57BL ; von Willebrand Factor/metabolism*

OBJECTIVETo study the effect of tetramethylpyrazine (TMP) on the vascular endothelial cell (VEC) related humoral factors, including endothelin (ET), factor VIII related antigen (i.e. von Willebrand factor, vWF) and thromboxane A2(TXA2) in patients of congenital heart disease with pulmonary hypertension (CHD-PH) during cardiopulmonary bypass (CPB), and explore the clinical physiopathologic significance of them.

METHODSThirty non-cyanotic patients of CHD-PH were randomly divided into the control group and the treated group. TMP was given to the treated group by intravenous dripping 3 mg/kg after anesthesia induction and adding 1 mg/kg in oxygenator during CPB. Blood samples were collected from radial artery at the time points of after anesthesia induction, 15 min after beginning CPB, 5 min after opening aorta, 20 min, 6 hrs and 24 hrs after stopping CPB, to determine the plasma contents of ET and vWF, as well as TXB2, the stable metabolite of TXA2. The pulmonary vascular reactivity 6 hrs (6h-PVR) after CPB and the mechanical ventilatory support time (VST) after operation were calculated.

RESULTSLevels of ET, vWF and TXB2 increased obviously during CPB, but the degree of increasing in the treated group was lower than that in the control group (P < 0.05), and the 6h-PVR and VST in the former were also lower than those in the latter respectively.

CONCLUSIONTMP could obviously reduce the production of ET, vWF and TXB2 during CPB and relieve the pulmonary vascular reactivity after operation, indicating that TMP could reduce the injury of CPB on VEC, and is benefit to enhance the efficacy of treatment.

Adolescent ; Adult ; Calcium Channel Blockers ; therapeutic use ; Cardiopulmonary Bypass ; Child ; Child, Preschool ; Endothelins ; blood ; Female ; Heart Defects, Congenital ; physiopathology ; surgery ; Humans ; Hypertension, Pulmonary ; drug therapy ; physiopathology ; Male ; Pyrazines ; therapeutic use ; Thromboxane B2 ; blood ; von Willebrand Factor ; metabolism

This study aims to observe the therapeutic effect of salidroside on cerebral ischemia-reperfusion(I/R) model rats, and to specifically explore the protection of salidroside on endothelial cell barrier after I/R and the mechanism. In the experiment, SD rats were randomized into sham group, model group, and high-, medium-, and low-dose(10, 5, and 2.5 mg·kg~(-1)) salidroside groups. The suture method was used to induce I/R in rats. The infarct area, neurobehavioral evaluation, and brain water content were used to evaluate the efficacy of salidroside. As for the experiment on the mechanism, high-dose and low-dose salidroside groups were designed. The pathological morphology was observed based on hematoxylin and eosin(HE) staining, and ultrastructure of vascular endothelial cells based on transmission electron microscopy. The content of nitric oxide(NO) in serum, four indexes of blood coagulation, and the content of von Willebrand factor(vWF) in plasma were measured. Western blot(WB) and immunofluorescence(IF) were employed to determine the expression of tight junction proteins(ZO-1, occluding, and claudin-1) and matrix metalloproteinase 9(MMP-9) in the cortex. The results showed that the model group had obvious neurological deficit, obvious infarct in the right brain tissue, and significant increase in water content in brain tissue compared with the sham group. Compared with the model group, high-dose and low-dose salidroside groups showed decrease in neurobehavioral score, and the high-, medium-, and low-dose salidroside groups demonstrated obviously small infarct area and significant decrease in water content in brain tissue. The results of HE staining and transmission electron microscopy showed that rats had necrosis of neurons, damage of original physiological structure of endothelial cells, and disintegration of the tight junction between endothelial cells after I/R compared with the sham group. Compared with the model group, the high-dose and low-dose salidroside groups showed alleviation of neuron injury and intact physiological structure of endothelial cells. The model group had significantly lower serum level of NO, significantly higher plasma levels of vWF and fibrinogen(FIB), and significantly shorter thrombin time(TT) and prothrombin time(PT) than the sham group. Compared with model group, the high-dose and low-dose salidroside groups increased the serum content of NO in serum, decreased the plasma levels of FIB and vWF, and significantly prolonged TT and PT. WB and IF results showed that the model group had significantly lower levels of ZO-1, occluding, and claudin-1 among endothelial cells and significantly higher level of MMP-9 than the sham group. Compared with the model group, high-dose and low-dose salidroside significantly increased the levels of ZO-1, occluding, and claudin-1 in the cortex. The above experimental results show that salidroside has clear therapeutic effect on I/R rats and protects the brain. To be specific, it alleviates the damage of endothelial cells by increasing NO synthesis in endothelial cells, inhibiting coagulation reaction and MMP-9 expression, up-regulating the expression of ZO-1, occludin, and claudin-1, thereby protecting the brain.
Animals ; Rats ; Matrix Metalloproteinase 9/metabolism* ; Endothelial Cells/metabolism* ; Reperfusion Injury/metabolism* ; Blood-Brain Barrier ; Claudin-1/therapeutic use* ; von Willebrand Factor/therapeutic use* ; Rats, Sprague-Dawley ; Brain Ischemia/metabolism* ; Cerebral Infarction ; Reperfusion ; Water/metabolism*

OBJECTIVETo observe the effect of Naoxintong Capsule (NC) on the vascular endothelial function and the infarct size of patients with acute myocardial infarction (AMI).

METHODSOne hundred and four patients with AMI were randomly assigned to the NC group (Group A, 36 cases), the Tongguan Capsule group (Group B, 32 cases), and the conventional Western medicine group (Group C, 36 cases). The conventional Western medicine was given to the three groups. NC was additionally given to Group A, and Tongguan Capsule was additionally given to Group B. The therapeutic course for all was 4 weeks. The plasma nitric oxide (NO), endothelin (ET), von Willebrand factor (vWF) were detected in the 3 groups before and after treatment. The inner diameter of brachial artery was examined by ultrasonograph. The flow-mediated dilation (FMD) and the nitroglycerin-mediated dilation (NMD) were calculated. The ECG QRS integral and the infarct size were assessed.

RESULTSThere was no significant difference in the vascular endothelial function, ECG QRS integral, or the infarct size among the three groups before treatment (P > 0.05). Compared with before treatment, NO and NMD obviously increased after treatment in Group A and Group B, while the vWF and the infarct size obviously decreased in Group A, all showing statistical difference (P < 0.05). Compared with those in Group C, the NO, FMD, NMD significantly increased and ET obviously decreased in Group A and B after treatment (P < 0.05). The ECG QRS integral and the infarct size also decreased, with statistically significant differences in Group A (P < 0.05). Better effects on improving NO, NMD, and vWF were obtained in Group A than in Group B (P < 0.05).

CONCLUSIONNC could reduce the infarct size of AMI patients possibly through improving the vascular endothelial function.

Adult ; Aged ; Drugs, Chinese Herbal ; therapeutic use ; Endothelins ; blood ; Endothelium, Vascular ; drug effects ; metabolism ; Female ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; drug therapy ; metabolism ; pathology ; Nitric Oxide ; blood ; Phytotherapy ; Young Adult ; von Willebrand Factor ; analysis

OBJECTIVEBy observing the effect of API 0134, an active ingredient of green chiretta, on platelet membrane glycoprotein (GP) in patients with hyperlipemia to explore the mechanism of the anti-platelet aggregation effect of API.

METHODSThe mean immunofluorescent intensity (MFI) of the platelet membrane glycoprotein GP II b/III a, GPIb, P-selectin (GMP-140) and von Willebrand's factor (vWF) in resting platelet, activated platelet (untreated or treated with API 0134 of different concentrations) were detected in 30 randomly selected patients with hyperlipemia, using immunofluorescent marker and flow cytometry.

RESULTSAPI of all concentrations (25 mg/L, 50 mg/L and 100 mg/L) could significantly decrease the MFI of GP II b/III a in a positive dose-dependent manner, as compared with that in activated platelet untreated with API; API of 50 mg/L and 100 mg/L could also reduce the MFI of GMP-140 and vWF in activated platelet (P < 0.01); but API of 100 mg/L showed insignificant influence on GPIb expression in activated platelet membrane.

CONCLUSIONAPI 0134 exerts obvious anti-platelet GP II b/III a effect on activated platelets, middle or large dose of API also shows inhibiting effect on GMP-140 and vWF expression in platelet.

Aged ; Andrographis ; chemistry ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Humans ; Hyperlipidemias ; blood ; drug therapy ; Male ; Middle Aged ; P-Selectin ; blood ; Phytotherapy ; Platelet Glycoprotein GPIIb-IIIa Complex ; metabolism ; von Willebrand Factor ; metabolism

OBJECTIVETo observe the clinical effect of Xuefu Zhuyu Capsule (XFZYC) in treating unstable angina pectoris (UAP) and to investigate its mechanism of protection on vascular endothelia.

METHODSSixty UAP patients were randomly assigned to two groups, the 30 in the treated group were treated by conventional therapy plus XFZYC, and the 30 in the control group treated by conventional therapy alone. The frequency and persistent time of angina pectois, dosage of nitroglycerin used, changes of electrocardiogram (ECG) were observed, and the plasma levels of endothelin (ET), nitric oxide (NO), von Willebrand factor (vWF), soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble intercellular adhesion molecule-1 (sICAM-1) were tested before and after the two-month therapeutic course.

RESULTS(1) The clinical symptoms as frequency and persistent time of angina pectoris in the treated group were bettered significantly after treatment and the dosage of nitroglycerin used decreased (all P < 0.01), showing significant difference when compared with those in the control group (P < 0.05). (2) The effective rates on UAP symptoms and ECG in the treated group were 86.7% and 76.7% respectively, which were significantly higher than those in the control group (70.0% and 63.3%, P < 0.05). (3) Laboratory examination showed in the control group, changes only displayed in the decrease of vWF and ET and increase of NO (all P < 0.05), while in the treated group, plasma levels of vWF, ET, sVCAM-1 and sICAM-1 after treatment significantly decreased and were lower than those in the control group (P < 0.01), but NO elevated significantly and was higher than that in the control group (P < 0.01).

CONCLUSIONSXFZYC is an effective Chinese patent medicine for treatment of UAP. It displays its effect on protecting vascular endothelia and anti-angina pectoris partially by decreasing the plasma levels of ET, vWF, sVCAM-1 and sICAM-1 and elevating the level of NO.

Adult ; Aged ; Aged, 80 and over ; Angina, Unstable ; blood ; drug therapy ; Capsules ; Drugs, Chinese Herbal ; therapeutic use ; Endothelins ; blood ; Female ; Humans ; Male ; Middle Aged ; Nitric Oxide ; blood ; Phytotherapy ; Vascular Cell Adhesion Molecule-1 ; blood ; von Willebrand Factor ; metabolism

OBJECTIVETo explore the protective effect and the mechanism of Puerarin Injection (PI) on myocardial ischemia reperfusion in patients with coronary heart disease (CHD) and angina pectoris (AP).

METHODSSeventy-eight patients with AP planned to receive the PTCA and stenting treatment were randomly divided and single-blindedly into the conventional group and the PI group. Based on the conventional treatment and pre-operational preparation, the PI group was given 200 ml of PI by intravenous dripping once a day, beginning from one week before operation, but to the conventional group, normal saline was given for instead. The condition of AP attack in balloon dilatatory stage of PTCA was observed and change of ST segment of ECG detected by a 12-lead ECG monitor. The blood levels of von Willebrand factor (vWF:Ag), nitric oxide (NO) and endothelin-1 (ET-1) were also observed before and after treatment.

RESULTSAs compared with those in the conventional group, number of patients having AP attack and ST segment change in PTCA process was lessened in the PI group, with blood levels of vWF:Ag and ET-1 obviously lower, and NO content obviously higher than those in the conventional group,

CONCLUSIONSPI could protect the myocardium in 2-3 days after ischemia reperfusion, one of the possible reasons is that PI can simulate the late phase of ischemic preconditioning, which may be related to its effect in lowering plasma vWF:Ag and ET-1, and increasing the serum NO content.

Angina Pectoris ; therapy ; Angioplasty, Balloon, Coronary ; Antigens ; blood ; Endothelin-1 ; blood ; Female ; Humans ; Infusions, Intravenous ; Isoflavones ; therapeutic use ; Male ; Middle Aged ; Myocardial Reperfusion Injury ; prevention & control ; Nitric Oxide ; blood ; Stents ; von Willebrand Factor ; immunology

OBJECTIVETo observe the effect of Tongxinluo Capsule on platelet activities and vascular endothelial functions as well as prognosis in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI) at different stages.

METHODS160 patients with acute coronary syndrome were randomly assigned to Tongxinluo (TXL) group (80 patients) and the conventional treatment group (80 patients). And 50 healthy subjects were set up as the health control group. Patients' plasma platelet activating factors (CD62p, CD63), and glucose protein (GP) IIb/IIIa, and endothelium-1 (ET-1), von Willebrand factor (vWF), nitric oxide (NO) levels, and endothelium dependent flow-mediated dilatation (FMD) were detected respectively. Patients in the TXL group orally took TXLC for six months. The aforesaid indices were re-detected in all patients after two months and six months. Comparison between before and after treatment in the same group and inter-group comparison were performed in the two groups.

RESULTSCompared with the health control group, CD62p, CD63, GPIIb/IIIa, vWF, and ET-1 levels increased significantly in ACS patients after PCI (all P<0.01), NO and FMD significantly decreased (P<0.01). CD62p, CD63, GPIIb/IIIa and, vWF also increased, and FMD decreased after PCI (all P<0.05), but insignificant difference was found in ET-1 and NO (P>0.05). In the TXL group and the conventional treatment group, the levels of CD62p, CD63, GPIIb/IIIa, vWF and ET-1 decreased significantly (P<0.05, P<0.01), NO and FMD increased (P<0.05, P<0. 01) when compared with before treatment. Compared with the conventional treatment group, the decrement of CD62p, CD63, GPIIb/IIIa and vWF (P<0.05, P<0.01), and the increment of FMD and NO (both P<0.05) were more obvious in the TXL group. The aforesaid indices were more obviously different between 6-month treatment and 2-month treatment in the TXL group and the conventional treatment group (P<0.05, P<0.01). Seven patients suffered from angina, six from heart failure, three from ventricular tachycardiac (VT)/ventricular fibrillation (VF), and two died suddenly in the conventional treatment group after six months of treatment, while only one suffered from angina, one from heart failure, and none from VT/VF or died suddenly in the TXL treatment group after 6 months of treatment.

CONCLUSIONTXL could be used in the prevention and treatment of coronary thrombosis, protect the vascular endothelial functions, as well as improve the prognosis of ACS patients after PCI.

Acute Coronary Syndrome ; blood ; therapy ; Aged ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Nitric Oxide ; blood ; Percutaneous Coronary Intervention ; Platelet Activation ; drug effects ; Platelet Glycoprotein GPIIb-IIIa Complex ; metabolism ; Prognosis ; von Willebrand Factor ; metabolism

OBJECTIVETo study the significance of plasma D-dimer and von Willebrand factor (vWF) and the therapeutic effect of compound glycyrrhizin in children with cytomegalovirus (CMV) hepatitis.

METHODSTwenty healthy children, 16 asymptomatic cases with CMV infection and 52 cases of CMV hepatitis (21 cholestatic and 31 non-cholestatic) were enrolled. The 52 children with CMV hepatitis were randomly administered with conventional treatment alone or conventional treatment plus compound glycyrrhizin treatment. Plasma D-dimer and vWF levels were measured before and after treatment.

RESULTSPlasma D-dimer and vWF levels in the CMV hepatitis group were markedly higher than those in the healthy control and asymptomatic CMV infection groups (P<0.01). The cholestatic hepatitis group had more increased plasma D-dimer and vWF levels compared with the non-cholestatic hepatitis group (P<0.01). Plasma D-dimer and vWF levels in the CMV hepatitis group were markedly reduced after conventional or compound glycyrrhizin treatment (P<0.01). Compound glycyrrhizin treatment decreased more significantly plasma D-dimer and vWF levels compared with the conventional treatment in children with CMV hepatitis (P<0.01).

CONCLUSIONSThe detection of plasma D-dimer and vWF is useful in the early assessment of liver damage in children with CMV hepatitis. Compound glycyrrhizin can decrease obviously plasma D-dimer and vWF levels and might thus provide protective effects against liver damage.

Child, Preschool ; Cytomegalovirus Infections ; blood ; drug therapy ; physiopathology ; Female ; Fibrin Fibrinogen Degradation Products ; analysis ; Glycyrrhizic Acid ; pharmacology ; therapeutic use ; Hepatitis, Viral, Human ; blood ; drug therapy ; physiopathology ; Humans ; Infant ; Liver Circulation ; Male ; von Willebrand Factor ; analysis

OBJECTIVETo evaluate the effect of Tongxinluo (TXL) Capsule on function of vascular endothelium in patients with unstable angina pectoris (UAP).

METHODSForty-six UAP patients were randomly divided into two group, the 28 patients in the treated group treated by conventional therapy plus TXL and the 18 patients in the control group treated by conventional therapy alone. Changes of blood levels of endothelin (ET), nitric oxide (NO), Von Willebrand factor (vWF), soluble vascular cell adhesive molecule-1 (sVCAM-1) and soluble intracellular adhesive molecule-1 (sICAM-1) from before treatment to after two months of treatment were observed, and the flow-mediated dilatation (FMD) in brachial artery was detected at the same time using ultrasonography.

RESULTSAfter treatment, the blood level of vWF and ET obviously decreased (P < 0.01), levels of NO and FMD increased (P < 0.05 or P < 0.01) in both groups. Levels of sVCAM-1 and sICAM-1 significantly decreased in the treated group (P < 0.01), while in the control group, no marked change was found in sVCAM-1 and sICAM-1 (P > 0.05). Compared with the control group after treatment, the levels of vWF, ET, sVCAM-1 and sICAM-1 in the treated group were lower (P < 0.01), and levels of NO and FMD were higher (P < 0.01).

CONCLUSIONTXL might protect vascular endothelium, improve clinical therapeutic effect by path of decreasing blood levels of ET, vWF and partial cellular adhesive factor, and increasing the level of NO.

Aged ; Angina, Unstable ; blood ; drug therapy ; Capsules ; Drugs, Chinese Herbal ; therapeutic use ; Endothelins ; blood ; Endothelium, Vascular ; drug effects ; physiopathology ; Female ; Humans ; Male ; Middle Aged ; Nitric Oxide ; blood ; Phytotherapy ; Vascular Cell Adhesion Molecule-1 ; blood ; von Willebrand Factor ; metabolism